WO1999046260A1 - New compounds - Google Patents

New compounds Download PDF

Info

Publication number
WO1999046260A1
WO1999046260A1 PCT/SE1999/000276 SE9900276W WO9946260A1 WO 1999046260 A1 WO1999046260 A1 WO 1999046260A1 SE 9900276 W SE9900276 W SE 9900276W WO 9946260 A1 WO9946260 A1 WO 9946260A1
Authority
WO
WIPO (PCT)
Prior art keywords
indol
acid salt
amino
quinoxalin
trifluoroacetic acid
Prior art date
Application number
PCT/SE1999/000276
Other languages
French (fr)
Inventor
Kostas Karabelas
Hans LÖNN
Peter Sjö
Original Assignee
Astrazeneca Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Priority to AU28638/99A priority Critical patent/AU2863899A/en
Publication of WO1999046260A1 publication Critical patent/WO1999046260A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems

Definitions

  • the present invention relates to novel quinoxalinones which are inhibitors of protein lcinase C.
  • the invention further relates to formulations comprising said inhibitors of protein kinase C, use thereof in medical therapy and in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • PLC Protein kinase C
  • PKC inhibitors e.g. isoquinoline sulphonamides, sphingosine and related sphingolipids, indolocarbazoles and bisindolyl- maleimides.
  • the present invention provides novel quinoxalinones which are PKC inhibitors.
  • the present invention further provides novel quinoxalinones for use in medical therapy, and more particularly in the treatment of inflammatory, immunological, broncho- pulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • the present invention also provides use of the compounds of the present invention in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • compositions comprising a compound according to the present invention, as active ingredient, together with a pharmaceutically acceptable adjuvant, diluent or carrier.
  • the present invention provides optionally substituted and/or annulated compounds of formula (I):
  • Rl is H, 2-amino-l -methyl-ethyl, 2-methylamino-ethyl, 2-amino-4-methyl-pentyl, piperidin-3-ylmethyl, piperidin-4-yl, 3-aminopropyl, 2-(2-amino-ethoxy)-ethyl or 5-amino- pentyl
  • R2 is H, halogen, or carboxyC 1-6 alkyl
  • R3 is C ⁇ -6 alkyl, N,N-diethylacetamid-2-yl, 4-cyanobenzyl, tetrahydro-furan-2-ylmethyl, 3-amino-propyl or 3-amino-butyl
  • R4 and R5 are each independently H, halogen, benzyloxy or carboxyQ. 6 alkyl
  • Preferred compounds are optionally substituted and/or annulated compounds comprising i) 3-[l-(3-Amino-propyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one or ii) 3-[ 1 -(4-Amino-butyl)- 1 H-indol-3-yl]-7 -phenyl- 1 H-quinoxalin-2-one
  • the present invention provides the compounds described in the Examples 1 to 155 hereto and salts thereof.
  • the most preferred compounds of the present invention are as follows:
  • Salts of the compounds according to the invention are preferably pharmaceutically acceptable salts.
  • Other, non-pharmaceutically acceptable salts may be useful as intermediates e.g. in the preparation of pharmaceutically acceptable salts or other compound of the present invention.
  • compounds of the present invention and pharmaceutical acceptable salts thereof can also reduce the generation of inflammatory mediators.
  • the compounds can inhibit oxygen radical generation and generation of pro- inflammatory cytokines in monocytes.
  • the compounds are especially useful as inhibitors of one or more cytokines selected from LL-l ⁇ , TNF- ⁇ , GM-CSF or IL-8.
  • the compounds of the invention are indicated for use in medical therapy. More particularly, the compounds of the invention are indicated for use in the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS- degenerative disorders.
  • inflammatory and/or immunological disorders such as the oral or topical treatment of airway diseases involving inflammatory conditions, e.g. asthma, bronchitis or atopic diseases, e.g. rhinitis or atopic dermatitis; inflammatory bowel diseases, e.g. Crohn's disease or colitis; autoimmune diseases e.g.
  • multiple sclerosis diabetes, atherosclerosis, psoriasis, systemic lupus erythematosus or rheumatoid arthritis; malignant diseases, e.g. skin or lung cancer; HIV infections or AIDS; or for inhibiting rejection of organs/transplants.
  • the compounds of the invention are also indicated for use in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
  • the present invention is also directed to a method for the treatment of an inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorder, wherein a therapeutically effective amount of a compound of the invention is administered to a mammal in the need of such treatment.
  • the dose of the compound to be administered will depend upon the relevant indication, the age, weight and sex of the patient and may be determined by a physician.
  • the dosage will preferably be in the range of from 0.1 mg/kg to 100 mg/kg.
  • the compounds may be administered topically, e.g. to the lung and/or the airways, in the form of solutions, suspensions, aerosols or dry powder formulations, e.g. formulations in
  • the inhaler device known as the Turbuhaler (trademark of Astra AB of Sweden), or systemically, e.g. by oral administration in the form of tablets, pills, capsules, syrups, powders or granules, or by parenteral administration, e.g. in the form of sterile parenteral solutions or suspensions, or by rectal administration, e.g. in the form of suppositories.
  • Compounds of the invention may be administered on their own or as a pharmaceutical composition comprising a compound of the invention in combination with a pharmaceutically acceptable diluent, adjuvant or carrier.
  • Particularly preferred are compositions not containing material capable of causing an adverse, e.g. an allergic, reaction.
  • Dry powder formulations and pressurized HFA aerosols of the compounds of the invention may be administered by oral or nasal inhalation.
  • the compound is desirably finely divided.
  • the finely divided compound preferably has a mass median diameter of less than 10 ⁇ m, and may be suspended in a propellant mixture with the assistance of a disper- sant, such as a C 8 -C20 fatty acid or salt thereof, (e.g. oleic acid), a bile salt, aphospholipid, an alkyl saccharide, a perfluorinated or polyethoxylated surfactant, or other pharmaceutically acceptable dispersant.
  • a disper- sant such as a C 8 -C20 fatty acid or salt thereof, (e.g. oleic acid), a bile salt, aphospholipid, an alkyl saccharide, a perfluorinated or polyethoxylated surfactant, or other pharmaceutically acceptable dispersant.
  • Compounds of the invention may also be administered by means of a dry powder inhaler.
  • the inhaler may be a single or a multi dose inhaler, and may be a breath actuated dry powder inhaler.
  • a carrier substance e.g. a mono-, di- or polysaccharide, a sugar alcohol, or an other polyol.
  • Suitable carriers are sugars, e.g. lactose, glucose, raffinose, melezitose, lactitol, maltitol, trehalose, sucrose, mannitol; and starch.
  • the finely divided compound may be coated by another substance.
  • the powder mixture may also be dispensed into hard gelatine capsules, each containing the desired dose of the active compound.
  • Another possibility is to process the finely divided powder into spheres which break up during the inhalation procedure.
  • This spheronized powder may be filled into the drug
  • a ® reservoir of a multidose inhaler e.g. that known as the Turbuhaler in which a dosing unit meters the desired dose which is then inhaled by the patient.
  • the active compound with or without a carrier substance, is delivered to the patient.
  • the active compound may be admixed with an adjuvant or a carrier, e.g. lactose, saccharose, sorbitol, mannitol; a starch, e.g. potato starch, corn starch or amylopectin; a cellulose derivative; a binder, e.g. gelatine orpolyvinylpyrrolidone, and/or a lubricant, e.g. magnesium stearate, calcium stearate, polyethylene glycol, a wax, paraffin, and the like, and then compressed into tablets.
  • the cores, prepared as described above may be coated with a concentrated sugar solution which may contain e.g. gum arabic, gelatine, talcum, titanium dioxide, and the like.
  • the tablet may be coated with a suitable polymer dissolved in a readily volatile organic solvent.
  • the compound may be admixed with e.g. a vegetable oil or polyethylene glycol.
  • Hard gelatine capsules may contain granules of the compound using either the above mentioned excipients for tablets. Also liquid or semisolid formulations of the drug may be filled into hard gelatine capsules.
  • Liquid preparations for oral application may be in the form of syrups or suspensions, for solutions containing the compound, the balance being sugar and a mixture of ethanol, water, glycerol and propylene glycol.
  • Such liquid preparations may contain colouring agents, flavouring agents, saccharine and/or carboxymethylcellulose as a thickening agent or other excipients known to those skilled in art.
  • the compounds of the invention may also be administered in conjunction with other compounds used for the treatment of the above conditions.
  • 'medical therapy' as used herein is intended to include prophylactic, diagnostic and therapeutic regimens carried out in vivo or ex vivo on humans or other mammals.
  • Polymeric imidazolide carbamate (3g, 3.0 mmol, prepared as described by Hauske, J. R.; Dorff, P. Tetrahedron Lett. 1995, 36, 1589-1592, from a Wang resin purchased from Rapp Polymere GmbH, Tubingen, Germany, 1.1 mmol/g,) was heated in DMF ( 25 ml) containing 3-piperidine methanol (1.38g, 12 mmol) at 90 °C for 13h. The resin was filtered and washed (3 times, 30ml) DMF, CH 2 C1 2 , MeOH, and dried in vacuum. Gel-phase 13 C- nmr (CDC1 3 ) showed formation of carbamate linked 3-piperidine methanol.
  • Oxalylchloride (25.9 ml, 0.3 mol) in CH 2 C1 2 (133ml) was added droppwise to DMSO in CH 2 C1 2 (133ml) during 30 min, at -78°C. After additional 15 min s-collidine (79ml, 0.6 mmol) in CH C1 2 (133ml) was added during 20 min, and 15 min later a part of the cool activated DMSO-solution (50 ml, approx. 30 mmol) was added to the dried carbamate linked 3-piperidine methanol resin (approx. 3 mmol), and the mixture was shaken over night at room temperature.
  • N-alkyl-l,2-diaminobenzene resin 75mg, 0.058 mmol
  • l-ethylindole-3-glyoxylic acid 79 mg, 0.36 mmol
  • DMSO DMSO
  • step b) The product of step b) (0.142 g, 0.253 mmol) was suspended in tetrahydrofuran (1 ml) and aqueous methylamine (40%, 1 ml) was added. After stirring overnight the solvent was removed in vacuo. The residue was washed with water and treated with glacial acetic acid to obtain the title compound after freeze drying as a yellow solid (0.111 g, 99%).

Abstract

The present invention relates to novel quinoxalinones which are inhibitors of protein kinase C. The invention further relates to formulations comprising said inhibitors of protein kinase C, use thereof in medical therapy and in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.

Description

NEW COMPOUNDS
FIELD OF THE INVENTION
The present invention relates to novel quinoxalinones which are inhibitors of protein lcinase C. The invention further relates to formulations comprising said inhibitors of protein kinase C, use thereof in medical therapy and in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
BACKGROUND OF THE INVENTION
Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine-specific protein kinases which play an important role in cellular growth control, regulation and differentiation.
Since the activation of PKC has been implicated in several human disease processes, including various forms of cancer, different forms of inflammatory and/or immunological disorders as well as some neurological disorders, inhibition of PKC could be of therapeutic value in treating these conditions.
Several classes of compounds have been identified as PKC inhibitors, e.g. isoquinoline sulphonamides, sphingosine and related sphingolipids, indolocarbazoles and bisindolyl- maleimides.
Although PKC inhibitors are described in the prior art, there is a need for specific anti- inflammatory and immunosuppressive compounds which are suitable for oral administration, and for inhalation. SUMMARY OF THE INVENTION
The present invention provides novel quinoxalinones which are PKC inhibitors.
The present invention further provides novel quinoxalinones for use in medical therapy, and more particularly in the treatment of inflammatory, immunological, broncho- pulmonary, cardiovascular, oncological or CNS-degenerative disorders.
The present invention also provides use of the compounds of the present invention in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
Also provided by the present invention are pharmaceutical compositions comprising a compound according to the present invention, as active ingredient, together with a pharmaceutically acceptable adjuvant, diluent or carrier.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides optionally substituted and/or annulated compounds of formula (I):
(I)
Figure imgf000004_0001
and salts thereof.
Specifically, the present invention provides compounds of formula (LI): (II)
Figure imgf000005_0001
wherein:
Rl is H, 2-amino-l -methyl-ethyl, 2-methylamino-ethyl, 2-amino-4-methyl-pentyl, piperidin-3-ylmethyl, piperidin-4-yl, 3-aminopropyl, 2-(2-amino-ethoxy)-ethyl or 5-amino- pentyl
R2 is H, halogen, or carboxyC1-6alkyl
R3 is Cι-6 alkyl, N,N-diethylacetamid-2-yl, 4-cyanobenzyl, tetrahydro-furan-2-ylmethyl, 3-amino-propyl or 3-amino-butyl
R4 and R5 are each independently H, halogen, benzyloxy or carboxyQ.6alkyl
and salts thereof.
Preferred compounds are optionally substituted and/or annulated compounds comprising i) 3-[l-(3-Amino-propyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one or ii) 3-[ 1 -(4-Amino-butyl)- 1 H-indol-3-yl]-7 -phenyl- 1 H-quinoxalin-2-one
and salts thereof.
More specifically, the present invention provides the compounds described in the Examples 1 to 155 hereto and salts thereof. The most preferred compounds of the present invention are as follows:
1 -(3- Amino-propy l)-3-(3-oxo-6-phenyl-3 ,4-dihydro-quinoxalin-2-y 1)- 1 H-indole-5- carboxylic acid methyl ester acetic acid salt,
3-[ 1 -(3-Amino-propyl)-6-benzyloxy- 1 H-indol-3-yl ]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-5-benzyloxy- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-5-bromo- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(4-Aπύno-butyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
and the corresponding free amines thereof and other pharmaceutically acceptable salts thereof.
Salts of the compounds according to the invention are preferably pharmaceutically acceptable salts. Other, non-pharmaceutically acceptable salts may be useful as intermediates e.g. in the preparation of pharmaceutically acceptable salts or other compound of the present invention.
Included within the scope of the present invention are all enol tautomers of compounds of the present invention as well as stereoisomers, pure and mixed racemates, and mixtures thereof. Compounds of the present invention and pharmaceutically acceptable salts thereof, are useful because they demonstrate pharmacological activity. In particular they demonstrate activity as kinase inhibitors, especially PKC inhibitors, e.g. as is shown by their activity in the in vitro assays described in Granet, R.A. et al, Analyt. Biochem. 1987; 163, 458-463; Olsson, H. et al, Cell Signal 1989, I, 405-410; Chakravarthy, B.R. et al, Analyt. Biochem. 1991, 196, 144-150 and Bergstrand, H et al, J. Pharm. Exp. Ther. 1992; 263(3). 1334-1346.
In appropriate cellular systems, compounds of the present invention and pharmaceutical acceptable salts thereof, can also reduce the generation of inflammatory mediators. For example, the compounds can inhibit oxygen radical generation and generation of pro- inflammatory cytokines in monocytes. The compounds are especially useful as inhibitors of one or more cytokines selected from LL-lβ, TNF-α, GM-CSF or IL-8.
The compounds of the invention are indicated for use in medical therapy. More particularly, the compounds of the invention are indicated for use in the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS- degenerative disorders. Preferably for oral or topical treatment of inflammatory and/or immunological disorders, such as the oral or topical treatment of airway diseases involving inflammatory conditions, e.g. asthma, bronchitis or atopic diseases, e.g. rhinitis or atopic dermatitis; inflammatory bowel diseases, e.g. Crohn's disease or colitis; autoimmune diseases e.g. multiple sclerosis, diabetes, atherosclerosis, psoriasis, systemic lupus erythematosus or rheumatoid arthritis; malignant diseases, e.g. skin or lung cancer; HIV infections or AIDS; or for inhibiting rejection of organs/transplants.
The compounds of the invention are also indicated for use in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
The present invention is also directed to a method for the treatment of an inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorder, wherein a therapeutically effective amount of a compound of the invention is administered to a mammal in the need of such treatment.
The dose of the compound to be administered will depend upon the relevant indication, the age, weight and sex of the patient and may be determined by a physician. The dosage will preferably be in the range of from 0.1 mg/kg to 100 mg/kg.
The compounds may be administered topically, e.g. to the lung and/or the airways, in the form of solutions, suspensions, aerosols or dry powder formulations, e.g. formulations in
® the inhaler device known as the Turbuhaler (trademark of Astra AB of Sweden), or systemically, e.g. by oral administration in the form of tablets, pills, capsules, syrups, powders or granules, or by parenteral administration, e.g. in the form of sterile parenteral solutions or suspensions, or by rectal administration, e.g. in the form of suppositories.
Compounds of the invention may be administered on their own or as a pharmaceutical composition comprising a compound of the invention in combination with a pharmaceutically acceptable diluent, adjuvant or carrier. Particularly preferred are compositions not containing material capable of causing an adverse, e.g. an allergic, reaction.
Dry powder formulations and pressurized HFA aerosols of the compounds of the invention may be administered by oral or nasal inhalation. For inhalation the compound is desirably finely divided. The finely divided compound preferably has a mass median diameter of less than 10 μm, and may be suspended in a propellant mixture with the assistance of a disper- sant, such as a C8-C20 fatty acid or salt thereof, (e.g. oleic acid), a bile salt, aphospholipid, an alkyl saccharide, a perfluorinated or polyethoxylated surfactant, or other pharmaceutically acceptable dispersant.
Compounds of the invention may also be administered by means of a dry powder inhaler. The inhaler may be a single or a multi dose inhaler, and may be a breath actuated dry powder inhaler. One possibility is to mix the finely divided compound with a carrier substance, e.g. a mono-, di- or polysaccharide, a sugar alcohol, or an other polyol. Suitable carriers are sugars, e.g. lactose, glucose, raffinose, melezitose, lactitol, maltitol, trehalose, sucrose, mannitol; and starch. Alternatively the finely divided compound may be coated by another substance. The powder mixture may also be dispensed into hard gelatine capsules, each containing the desired dose of the active compound.
Another possibility is to process the finely divided powder into spheres which break up during the inhalation procedure. This spheronized powder may be filled into the drug
® reservoir of a multidose inhaler, e.g. that known as the Turbuhaler in which a dosing unit meters the desired dose which is then inhaled by the patient. With this system the active compound, with or without a carrier substance, is delivered to the patient.
For oral administration the active compound may be admixed with an adjuvant or a carrier, e.g. lactose, saccharose, sorbitol, mannitol; a starch, e.g. potato starch, corn starch or amylopectin; a cellulose derivative; a binder, e.g. gelatine orpolyvinylpyrrolidone, and/or a lubricant, e.g. magnesium stearate, calcium stearate, polyethylene glycol, a wax, paraffin, and the like, and then compressed into tablets. If coated tablets are required, the cores, prepared as described above, may be coated with a concentrated sugar solution which may contain e.g. gum arabic, gelatine, talcum, titanium dioxide, and the like. Alternatively, the tablet may be coated with a suitable polymer dissolved in a readily volatile organic solvent.
For the preparation of soft gelatine capsules, the compound may be admixed with e.g. a vegetable oil or polyethylene glycol. Hard gelatine capsules may contain granules of the compound using either the above mentioned excipients for tablets. Also liquid or semisolid formulations of the drug may be filled into hard gelatine capsules.
Liquid preparations for oral application may be in the form of syrups or suspensions, for solutions containing the compound, the balance being sugar and a mixture of ethanol, water, glycerol and propylene glycol. Optionally such liquid preparations may contain colouring agents, flavouring agents, saccharine and/or carboxymethylcellulose as a thickening agent or other excipients known to those skilled in art.
The compounds of the invention may also be administered in conjunction with other compounds used for the treatment of the above conditions.
The term 'medical therapy' as used herein is intended to include prophylactic, diagnostic and therapeutic regimens carried out in vivo or ex vivo on humans or other mammals.
EXAMPLES
The following Examples are intended to illustrate, but in no way limit the scope of the invention.
All reactions were performed in dried glassware under Ar or N2 unless otherwise noted. Tetrahydrofuran was distilled from sodium/benzophenone. Dimethyl formamide (DMF) was distilled from calcium hydride, or dried over molecular sieves. Other solvents and all commercial reagents were laboratory grade and used as received.
1H - NMR spectra were recorded on a Varian XL-300, Varian Unity Inova 400 or a Varian Unity Inova 500 instrument. The central solvent peaks of chloroform-^ (c^ 7.27 ppm) and dimethyl sulphoxide- g (δfj 2.50 ppm) were used as internal references. Low-resolution mass spectra and accurate mass determinations were recorded on an Autospec-Q, Fisons Analytical, double focusing sector instrument equipped with a LSIMS interface. Low resolution mass spectra were also obtained on a Hewlett Packard 1100 LC-MS system equipped with APCI ionisation chamber. DMSO is dimethylsulfoxide, MeOH is methanol and HOAc is acetic acid. Example 1
3-( 1 -Ethyl- 1 H-indol-3-yl)- 1 -piperidin-3-ylmethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
Polymeric imidazolide carbamate (3g, 3.0 mmol, prepared as described by Hauske, J. R.; Dorff, P. Tetrahedron Lett. 1995, 36, 1589-1592, from a Wang resin purchased from Rapp Polymere GmbH, Tubingen, Germany, 1.1 mmol/g,) was heated in DMF ( 25 ml) containing 3-piperidine methanol (1.38g, 12 mmol) at 90 °C for 13h. The resin was filtered and washed (3 times, 30ml) DMF, CH2C12, MeOH, and dried in vacuum. Gel-phase 13C- nmr (CDC13) showed formation of carbamate linked 3-piperidine methanol.
Oxalylchloride (25.9 ml, 0.3 mol) in CH2C12 (133ml) was added droppwise to DMSO in CH2C12 (133ml) during 30 min, at -78°C. After additional 15 min s-collidine (79ml, 0.6 mmol) in CH C12 (133ml) was added during 20 min, and 15 min later a part of the cool activated DMSO-solution (50 ml, approx. 30 mmol) was added to the dried carbamate linked 3-piperidine methanol resin (approx. 3 mmol), and the mixture was shaken over night at room temperature. The resin was filtered and washed (3 times, 50ml) CH2C12, THF-H2O-pyridine-6:2:l, THF, CH2C12, MeOH, and dried in vacuum. Gel-phase 13C-nmr (CDC13) showed oxidation of the carbamate linked 3-piperidine methanol.
A solution of 1 ,2-phenylenediamine ( 276 mg, 2.55mmol) and sodium triacetoxy borohydride (540 mg, 2.55 mmol) in DMF-HOAc (10:1, 8.5 ml) was added to the oxidised resin bound product (850 mg, 0.81 mmol), and the mixture was shaken over night at room temperature. The resin was filtered and washed (3 times, 10ml) DMF, THF-H2O-NEt3- 6:2:1, DMF, CH2C12, MeOH, and dried in vacuum. Gel-phase I3C-nmr (CDC13) showed formation of N-alkylated 1,2-diaminobenzene.
The N-alkyl-l,2-diaminobenzene resin (75mg, 0.058 mmol) and l-ethylindole-3-glyoxylic acid (79 mg, 0.36 mmol) in DMSO (0.28 ml) was heated at 100 °C for 1 h. The resin was 10
filtered and washed (4 times, 1ml) DMF, CH2Cl2-MeCN- 1 : 1 , and reacted in CH2C12- MeCN-1: 1(0.4 ml) with TFA-Me2S-H2O-95:5:5 (0.8 ml) for 0.5 h. Water (0.27 ml) was added, after 5 min the resin was filtered and washed twice with CH2Cl2-MeCN (1: 1, 1 ml). The combined filtrate and washings were concentrated and coevaporated with MeCN and the residue was dried in vacuum to give the title product (26 mg, 90%), purity 63% (HPLC, 254 nm). LC/APCI-MS showed the title product being the major component with m/z 387 [MH+].
An analytically pure sample of the corresponding free amine was obtained by silica gel chromatography (CH2Cl2-MeOH-NEt3-100:33: l).
1H-NMR of the free amine (500 MHz, DMSO-^6 ): δ 1.31 (IH, m), 1.32 (IH, m), 1.44 (3H, t, J7.2 Hz), 1.62 (IH, m), 1.75 (IH, m), 2.05 (IH, m), 2.47 (IH, dd, J 10.0, 11.0 Hz), 2.50 (IH, m), 2.85 (IH, m), 2.87 (IH, m), 4.21 (IH, dd, J 13.6, 6.4 Hz), 4.34 (IH, dd, J 13.6, 8.3 Hz), 4.35 (2H, q, J 12 Hz), 7.26-7.32 (2H, m), 7.39 (IH, br t, J 1A Hz), 7.54
(IH, br t, J 1.1 Hz), 7.61 (IH, m), 7.62 (IH, m), 7.93 (IH, dd, / 7.9, 1.4 Hz), ), 8.92 (IH, br d, 77.7 Hz), 8.96 (lH, s).
Example 2
3-[l-(3-Amino-propyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
a) { l-[3-(l,3-Dioxo-l,3-dihydro-isoindol-2-yl)-propyl]-lH-indol-3-yl}-oxo-acetic acid 2,5- dioxo-pyrrolidin-1-yl ester
l-[3-(l,3-Dioxo-l,3-dihydroisoindol-2-yl)-ρropyl]-lH-indol (1.00 g, 3.29 mmol) was dissolved in dichloromethane (10 ml) and cooled to 0°C. Oxalylchloride (0.28 ml, 3.29 mmol) was added and the reaction kept at 0°C for 30 minutes before the addition of N- hydroxysuccinimide (0.38 g, 3.29 mmol) followed by careful addition of pyridine (0.53 ml, 6.57 mmol). 11
After stirring the reaction for 1 hour at room temperature brine (5%, 10 ml) was added and the phases separated, the organic phase was washed with brine (5%, 2 x 10 ml), dried over Na2SO4 followed by removal of the solvent in vacuo. Crystallisation of the crude product from ethyl acetate - hexane yields the title product, 1.06 g (69%).
Η-NMR (500 MHz, CDC13): δ 2.36 (2H, p, 76.9 Hz), 2.93 (4H, s), 3.82 (2H, t, 76.5 Hz), 4.29 (2H, t, 77.5 Hz), 7.33-7.44 (3H, m), 7.70-7.75 (2H, m), 7.78-7.83 (2H, m), 8.32-8.36 (lH, m), 8.50 (lH, s).
FAB-MS: m/z 474 [MH+]
b) 2- { 3-[3-(3-Oxo-8-phenyl-3,4-dihydro-quinoxalin-2-yl)-indol- 1 -yl ropyl } -isoindole- 1,3-dione l,2-Diamino-3-phenylbenzene (0.135 g, 0.57 mmol) and the product of step a) (0.250 g, 0.53 mmol) was dissolved in tetrahydrofuran (2.5 ml). Stirring overnight gives a yellow precipitate that was filtered off and washed with tetrahydrofuran/diethylether yielding the sub-title product (0.141 g, 51%).
1H-NMR (400 MHz, OMSO-d6): δ 2.16 (2H, p, 76.9 Hz), 3.67 (2H, t, 76.7 Hz), 4.43 (2H, t, 77.3 Hz), 6.77 (IH, t, 77.8 Hz), 6.95 (IH, dd, 7 1.3, 7.5 Hz), 7.28-7.55 (8H, m), 7.70- 7.76 (IH, m), 7.79-7.88 (4H, m), 8.27-8.34 (IH, m), 8.94 (IH, s), 9.97 (IH, s).
The product of step b) (0.142 g, 0.253 mmol) was suspended in tetrahydrofuran (1 ml) and aqueous methylamine (40%, 1 ml) was added. After stirring overnight the solvent was removed in vacuo. The residue was washed with water and treated with glacial acetic acid to obtain the title compound after freeze drying as a yellow solid (0.111 g, 99%).
1H-NMR (400 MHz, DMSO- ): δ 1.90 (2H, q, 76.7 Hz), 2.58 (2H, t, 76.9 Hz), 4.35 (2H, t, 77.1 Hz), 6.84 (IH, t, 77.6 Hz), 7.18 (IH, t, 78.1 Hz), 7.30 (IH, d, 77.6 Hz), 7.35 (IH, 12
d, 78.2 Hz), 7.49 (IH, t, 78.2 Hz), 7.50-7,57 (4H, m), 7.62-7.67 (2H, m), 8.17 (IH, d, 7 8.3 Hz), 8.96 (lH, s).
FAB-MS: m/z 395.1 [MH+].
The following examples were synthesised following the methods described above:
Example 3
1 -(6- Amino-hexyl)-6,7-dichloro-3-[ 1 -(3-methoxy-benzyl)- 1 H-indol-3-yl]- 1 H-quinoxalin- 2-one trifluoroacetic acid salt
FAB-MS: m/z 550 [MH+]
Example 4
1 -(5- Amino-pentyl)-6,7-dichloro-3-[ 1 -(3-methoxy-benzyl)- 1 H-indol-3-yl]- 1 H-quinoxalin- 2-one trifluoroacetic acid salt
FAB-MS: m/z 536 [MH+]
Example 5
l-(3-Hydroxymethyl-benzyl)-3-(lH-indol-3-yl)-6,7-dimethyl-lH-quinoxalin-2-one
FAB-MS: m/z 410 [MH+]
Example 6
1 -[3-(4-Hydroxy-phenyl)-propyl]-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one 13
FAB-MS: m/z 424 [MH+]
Example 7
3-( 1 H-Indol-3-yl)-6,7-dimethyl- 1 -(2-piperazin- 1 -yl-ethyl)- 1 H-quinoxalin-2-onebis trifluoroacetic acid salt
FAB-MS: m/z 402 [MH+]
Example 8
l-[2-(2-Amino-ethoxy)-ethyl]-3-(lH-indol-3-yl)-6,7-dimethyl-lH-quinoxalin-2-one trifluoroacetic acid salt FAB-MS: m/z 377 [MH+]
Example 9
1 -(2- Amino-ethy I)-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
FAB-MS: m/z 333 [MH+]
Example 10
1 -(2- Amino- 1 -methyl-ethyl)-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
FAB-MS: m/z 347 [MH+] 14
Example 11
1 -(4- Amino-cyclohexyl)-3-( 1 H-indol-3-yl)-6,7-dimethy 1- 1 H-quinoxalin-2-one trifluoroacetic acid salt
FAB-MS: m/z 387 [MH+]
Example 12
3-[l-(3-Amino-propyl)-6-nitro-lH-indol-3-yl]-lH-pyrido[2,3-b]pyrazin-2-one acetic acid salt
FAB-MS: m/z 365 [MH+]
Example 13
3-[ 1 -(3-Amino-propyl)-6-nitro- 1 H-indol-3-yl ]-6,7-dimethyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 392 [MH+]
Example 14
2-[l-(3-Amino-propyl)-6-nitro-lH-indol-3-yl]-4H-pyrido[3,4-b]pyrazin-3-one acetic acid salt
FAB-MS: m/z 365 [MH+]
Example 15 15
3-[ 1 -(3-Amino-propyl)-6-nitro- 1 H-indol-3-yl]-7-trifluoromethyl- lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 432 [MH+]
Example 16
3-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-lH-pyrido[2,3-b]pyrazin-2-one acetic acid salt
FAB-MS: m/z 347 [MH+]
Example 17
3-[ 1 -(3-Amino-propyl)-7 -ethyl- lH-indol-3-yl ]-6,7-dimethyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 375 [MH+]
Example 18
3-[ 1 -(3- Amino-propyl)-7-ethyl- 1 H-indol-3-yl]-6,7-dichloro- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS : m/z 416 [MH+]
Example 19
2-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-4H-pyrido[3,4-b]pyrazin-3-one acetic acid salt 16
FAB-MS: m/z 348 [MH+]
Example 20
2-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-4H-pyrido[3,4-b]pyrazin-3-one acetic acid salt
FAB-MS: m/z 361 [MH+]
Example 21
3-[ 1 -(3- Amino-propyl)-7-ethyl- 1 H-indol-3-yl]-7-trifluoromethy 1- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 415 [MH+]
Example 22
3-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-7-nitro-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 392 [MH+]
Example 23
3-[5-(3-Aminomethyl-benzyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-7-phenyl-lH-quinoxalin- 2-one acetic acid salt
FAB-MS: m/z 501.6 [MH+] 17
Example 24
3-[5-(3-Amino-propyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 439.5 [MH+]
Example 25
3-[l-(3-Amino-propyl)-5-dibenzylamino-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 590.7 [MH+]
Example 26
3-[ 1 -(3-Amino-propyl)-2-(4-chloro-phenyl)- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 506.0 [MH+]
Example 27
3-[l-(3-Amino-propyl)-2-methyl-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 409.5 [MH+]
Example 28 18
1 -(3- Amino-propyl)-3-(3-oxo-6-phenyl-3 ,4-dihydro-quinoxalin-2-y 1)- 1 H-indole-5- carboxylic acid methyl ester acetic acid salt
FAB-MS: m z 453.5 [MH+]
Example 29
3-[ 1 -(3-Amino-propyl)-6-nitro- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 440.5 [MH+]
Example 30
3-[l-(3-Amino-propyl)-5-methoxy-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 425.5 [MH+]
Example 31
3-[5-(3-Aminomethyl-benzyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-5-phenyl-lH-quinoxalin- 2-one acetic acid salt
FAB-MS : m/z 501.6 [MH+]
Example 32
3-[5-(3-Amino-ρropyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt 19
FAB-MS: m/z 439.5 [MH+]
Example 33
3-[ 1 -(3-Amino-propyl)-5-dibenzylamino- 1 H-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 590.7 [MH+]
Example 34
3-[ 1 -(3- Amino-propyl)-2-methyl- 1 H-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 409.5 [MH+]
Example 35
l-(3-Amino-propyl)-3-(3-oxo-8-phenyl-3,4-dihydro-quinoxalin-2-yl)-lH-indole-5- carboxylic acid methyl ester acetic acid salt
FAB-MS: m/z 453.5 [MH+]
Example 36
3-[l-(3-Amino-propyl)-6-nitro-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 440.5 [MH+] 20
Example 37
3-[l-(3-Amino-propyl)-5-methoxy-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 425.5 [MH+]
Example 38
3-[l-(3-Amino-propyl)-6-benzyloxy-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 501.6 [MH+]
Example 39
3-[ 1 -(3- Amino-propyl)-5-benzyloxy- 1 H-indol-3-y l]-7 -phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 501.6 [MH+]
Example 40
3-[l-(3-Aπύno-propyl)-5-bromo-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 473.0, 475.0 [MH+] 21
Example 41
3-[ 1 -(3- Amino-propyl)-2-ethyl- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 423.5 [MH+]
Example 42
3-[l-(4-Amino-butyl)-2-benzyl-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 499.6 [MH+]
Example 43
3-[ 1 -(6-Aminomethyl-pyridin-2-ylmethyl)- lH-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 458.5 [MH+]
Example 44
3-[ 1 -(4- Aminomethyl-benzy 1)- lH-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 457.6 [MH+] 22
Example 45
3-[ 1 -(3- Aminomethyl-benzy 1)- 1 H-indol-3-yl ]-7 -phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 457.6 [MH+]
Example 46
3-[l-(4-Amino-butyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 409.5 [MH+]
Example 47
3-[l-(3-Amino-propyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 395.5 [MH+]
Example 48
3-[ 1 -(3-Amino-propyl)-6-benzyloxy- lH-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 501.6 [MH+]
Example 49
3-[l-(3-Amino-propyl)-5-benzyloxy-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt 23
FAB-MS: m/z 501.6 [MH+]
Example 50
3-[l-(3-Amino-propyl)-5-bromo-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 473.0, 475.0 [MH+]
Example 51
3-[ 1 -(3-Amino-propyl)-2-ethyl- lH-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 423.5 [MH+]
Example 52
3-[ 1 -(4- Amino-butyl)-2-benzyl- 1 H-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 499.6 [MH+]
Example 53
3-[ 1 -(4- Aminomethyl-benzy 1)- 1 H-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 457.6 [MH+] 24
Example 54
3-[ 1 -(3-Aminomethyl-benzyl)- lH-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 457.6 [MH+]
Example 55
3-[l-(4-Amino-butyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 409.5 [MH+]
Example 56
3-[l-(3-Amino-propyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
FAB-MS: m/z 395.5 [MH+]
Example 57
1 -(2- Amino- 1 -methyl-ethyl)-3-( 1 -ethyl- 1 H-indol-3-y 1)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 347 [MH+]
Example 58
2-.{ 3-[4-(2- Amino- 1 -methy l-ethyl)-3-oxo-3 ,4-dihydro-quinoxalin-2-y l]-indol- 1 -y 1 } -N,N- diethyl-acetamide trifluoroacetic acid salt 25
APCI-MS: 432 [MH+]
Example 59
4- { 3-[4-(2- Amino- 1 -methyl-ethy l)-3-oxo-3 ,4-dihydro-quinoxalin-2-y l]-indol- 1 -y Imethy 1 } - benzonitrile trifluoroacetic acid salt
APCI-MS: 434 [MH+]
Example 60
l-(2-Amino-l-methyl-ethyl)-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 403 [MH+]
Example 61
3-( 1 -Ethyl- 1 H-indol-3-y 1)- 1 -(2-methy lamino-ethyl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 347 [MH+]
Example 62
N,N-Diethyl-2-{ 3-[4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 - yl} -acetamide trifluoroacetic acid salt
APCI-MS: 432 [MH+] 26
Example 63
4-{3-[4-(2-Methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-ylmethyl}- benzonitrile trifluoroacetic acid salt
APCI-MS: 434 [MH+]
Example 64
l-(2-Methylamino-ethyl)-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 403 [MH+]
Example 65
1 -(2- Amino-4-methyl-pentyl)-3-( 1 -ethyl- 1 H-indol-3-y 1)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 389 [MH+]
Example 66
2- { 3-[4-(2-Amino-4-methyl-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -yl } -N,N- diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 474 [MH+] 27
Example 67
4-{3-[4-(2-Amino-4-methyl-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- y Imethy l}-benzonitrile trifluoroacetic acid salt
APCI-MS: 476 [MH+]
Example 68
1 -(2- Amino-4-methyl-pentyl)-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 445 [MH+]
3-( 1 -Ethyl- 1 H-indol-3-yl)- 1 -piperidin-3-ylmethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 387 [MH+]
Example 70
N,N-Diethyl-2-[3-(3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]- acetamide trifluoroacetic acid salt
APCI-MS: 472 [MH+]
4-[3-(3-Oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l-ylmethyl]- benzonitrile trifluoroacetic acid salt
APCI-MS: 474 [MH+] 28
Example 72
l-Piperidin-3-ylmethyl-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH-quinoxalin- 2-one trifluoroacetic acid salt
APCI-MS: 443 [MH+]
Example 73
3-(l -Ethyl- lH-indol-3-yl)-l-piperidin-4-yl-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 373 [MH+]
Example 74
N,N-Diethyl-2-[3-(3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]- acetamide trifluoroacetic acid salt
APCI-MS: 458 [MH+]
Example 75
4-[3-(3-Oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-ylmethyl]-benzonitrile trifluoroacetic acid salt
APCI-MS: 460 [MH+] 29
Example 76
1 -Piperidin-4-yl-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 429 [MH+]
Example 77
1 -(3- Amino-propyl)-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 347 [MH+]
Example 78
2- { 3-[4-(3- Amino-propyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -yl } -N,N-diethyl- acetamide trifluoroacetic acid salt
APCI-MS: 432 [MH+]
Example 79
4-{3-[4-(3-Amino-propyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-ylmethyl}- benzonitrile trifluoroacetic acid salt
APCI-MS: 434 [MH+] 30
Example 80
1 -(3- Amino-propyl)-3- [ 1 -(tetrahydro-furan-2-y Imethyl)- 1 H-indol-3-y 1]- 1 H-quinoxalin-2- one trifluoroacetic acid salt
APCI-MS: 403 [MH+]
Example 81
1 -[2-(2- Amino-ethoxy)-ethyl]-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 377 [MH+]
Example 82
2-(3- { 4-[2-(2-Amino-ethoxy)-ethyl]-3-oxo-3,4-dihydro-quinoxalin-2-yl } -indol- 1 -yl)-N,N- diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 462 [MH+]
Example 83
4-(3- { 4-[2-(2- Amino-ethoxy )-ethyl]-3-oxo-3 ,4-dihydro-quinoxalin-2-yl } -indol- 1 - ylmethyl)-benzonitrile trifluoroacetic acid salt
APCI-MS: 464 [MH+] 31
Example 84
1 -[2-(2-Amino-ethoxy)-ethyl]-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 433 [MH+]
Example 85
l-(5-Amino-pentyl)-3-(l -ethyl- lH-indol-3-yl)-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 375 [MH+]
Example 86
2- { 3-[4-(5- Amino-pentyl)-3-oxo-3 ,4-dihydro-quinoxalin-2-yl]-indol- 1 -yl } -N,N-diethy 1- acetamide trifluoroacetic acid salt
APCI-MS: 460 [MH+]
Example 87
4- { 3-[4-(5-Amino-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -ylmethyl } - benzonitrile trifluoroacetic acid salt
APCI-MS: 462 [MH+] 32
Example 88
1 -(5- Amino-pentyl)-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H-quinoxalin-2- one trifluoroacetic acid salt
APCI-MS: 431 [MH+]
Example 89
1 -(2- Amino- 1 -methyl-ethyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 415, 417 [MH+]
Example 90
2-{3-[4-(2-Amino-l-methyl-ethyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- l-yl}-N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 500, 502 [MH+]
Example 91
4-{3-[4-(2-Amino-l-methyl-ethyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -ylmethy 1 } -benzonitrile trifluoroacetic acid salt
APCI-MS: 502, 504 [MH+] 33
Example 92
1 -(2- Amino- 1 -methyl-ethy l)-6,7-dichloro-3- [ 1 -(tetrahydro-furan-2-y Imethyl)- 1 H-indol-3- yl]-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 471, 473 [MH+]
Example 93
6,7-Dichloro-3-(l-ethyl-lH-indol-3-yl)-l-(2-methylamino-ethyl)-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 415, 417 [MH+]
Example 94
2-{3-[6,7-Dichloro-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- yl}-N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 500, 502 [MH+]
Example 95
4-{3-[6,7-Dichloro-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- ylmethylj-benzonitrile trifluoroacetic acid salt
APCI-MS: 502, 504 [MH+] 34
Example 96
6,7-Dichloro-l-(2-methylamino-ethyl)-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]- lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 471, 473 [MH+]
Example 97
1 -(2- Amino-4-methyl-pentyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 457, 459 [MH+]
Example 98
2- { 3-[4-(2- Amino-4-methyl-penty l)-6,7-dichloro-3-oxo-3 ,4-dihydro-quinoxalin-2-y 1]- indol-l-yl}-N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 542, 544 [MH+]
Example 99
4-{3-[4-(2-Amino-4-methyl-pentyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]- indol- 1 -ylmethy 1 } -benzonitrile trifluoroacetic acid salt
APCI-MS: 544, 546 [MH+] 35
Example 100
l-(2-Amino-4-methyl-pentyl)-6,7-dichloro-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3- yl]-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 513, 515 [MH+]
Example 101
6,7-Dichloro-3-( 1 -ethyl- 1 H-indol-3-y 1)- 1 -piperidin-3-y Imethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 455, 457 [MH+]
Example 102
2-[3-(6,7-Dichloro-3-oxo-4-piperidin-3-ylmethyl-3 ,4-dihydro-quinoxalin-2-yl)-indol- 1 -yl]- N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 540, 542 [MH+]
Example 103
4-[3-(6,7-Dichloro-3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l- ylmethyl]-benzonitrile trifluoroacetic acid salt APCI-MS: 542, 544 [MH+] 36
Example 104
6,7-Dichloro-l-piperidin-3-ylmethyl-3-[l-(tetrahydro-furan-2-y Imethyl)- lH-indol-3-yl]- lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 511, 513 [MH+]
Example 105
6,7-Dichloro-3-( 1 -ethyl- 1 H-indol-3-y 1)- 1 -piperidin-4-y 1- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 441, 443 [MH+]
Example 106
2-[3-(6,7-Dichloro-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]-N,N- diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 526, 528 [MH+]
Example 107
4-[3-(6,7-Dichloro-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-ylmethyl]- benzonitrile trifluoroacetic acid salt
APCI-MS: 528, 530 [MH+] 37
Example 108
6,7-Dichloro- 1 -piperidin-4-yl-3-[ 1 -(tetrahydro-furan-2-y Imethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 497, 499 [MH+]
Example 109
1 -(3- Amino-propyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 415, 417 [MH+]
Example 110
2- { 3-[4-(3- Amino-propyl)-6,7-dichloro-3-oxo-3 ,4-dihydro-quinoxalin-2-y 1] -indol- 1 -y 1 } - N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 500, 502 [MH+]
Example 111
4-{3-[4-(3-Amino-propyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- ylmethyl}-benzonitrile trifluoroacetic acid salt
APCI-MS: 502, 504 [MH+] 38
Example 112
1 -(3- Amino-propyl)-6,7-dichloro-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-y 1]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 471, 473 [MH+]
Example 113
1 -[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-( 1 -ethyl- lH-indol-3-yl)- lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 445, 447 [MH+]
Example 114
2-(3-{4-[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl}- indol-l-yl)-N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 530, 532 [MH+]
Example 115
4-(3-{4-[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl}- indol- l-ylmethyl)-benzonitrile trifluoroacetic acid salt
APCI-MS: 532, 534 [MH+] 39
Example 116
1 -[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3- yl]-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 501, 503 [MH+]
Example 117
1 -(5- Amino-pentyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 443, 445 [MH+]
Example 118
2- { 3-[4-(5-Amino-pentyl)-6,7-dichloro-3-oxo-3 ,4-dihydro-quinoxalin-2-yl]-indol- 1 -y 1 } - N,N-diethyl-acetamide trifluoroacetic acid salt
APCI-MS: 528, 530 [MH+]
Example 119
4- { 3-[4-(5-Amino-pentyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 - ylmethyl}-benzonitrile trifluoroacetic acid salt
APCI-MS: 530, 532 [MH+] 40
Example 120
1 -(5- Amino-penty l)-6,7-dichloro-3-[ 1 -(tetrahydro-furan-2-ylmethy 1)- 1 H-indol-3-y 1] - 1 H- quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 499, 501 [MH+]
Example 121
4-(2- Amino- 1 -methyl-ethyl)-2-( 1 -ethyl- 1 H-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 405 [MH+]
Example 122
4-(2- Amino- 1 -methyl-ethy l)-2-( 1 -diethylcarbamoy Imethyl- 1 H-indol-3-yl)-3-oxo-3 ,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 490 [MH+]
Example 123
4-(2- Amino- 1 -methyl-ethy l)-2-[ 1 -(4-cyano-benzyl)- 1 H-indol-3-yl]-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 492 [MH+] 41
Example 124
4-(2-Amino-l-methyl-ethyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 461 [MH+]
Example 125
2-( 1 -Ethyl- 1 H-indol-3-yl)-4-(2-methylamino-ethyl)-3-oxo-3 ,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 405 [MH+]
Example 126
2-(l-Diethylcarbamoylmethyl-lH-indol-3-yl)-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 490 [MH+]
Example 127
2-[l-(4-Cyano-benzyl)-lH-indoI-3-yl]-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 492 [MH+] 42
Example 128
4-(2-Methylamino-ethyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 461 [MH+]
Example 129
4-(2-Amino-4-methyl-pentyl)-2-(l-ethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 447 [MH+]
Example 130
4-(2-Amino-4-methyl-pentyl)-2-(l-diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 532 [MH+]
Example 131
4-(2-Amino-4-methyl-pentyl)-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 534 [MH+] 43
Example 132
4-(2-Amino-4-methyl-pentyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]- 3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 503 [MH+]
Example 133
2-( 1 -Ethyl- 1 H-indol-3-yl)-3-oxo-4-piperidin-3-ylmethyl-3 ,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 445 [MH+]
Example 134
2-( 1 -Diethylcarbamoylmethyl- 1 H-indol-3-yl)-3-oxo-4-ρiρeridin-3-ylmethyl-3 ,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 530 [MH+]
Example 135
2-[l-(4-Cyano-benzyl)-lH-indol-3-yl]-3-oxo-4-ρiρeridin-3-ylmethyl-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 532 [MH+] 44
Example 136
3-Oxo-4-piperidin-3-ylmethyl-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 501 [MH+]
Example 137
2-(l -Ethyl- lH-indol-3-yl)-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 431 [MH+]
Example 138
2-(l-Diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-4-piperidin-4-yl-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 516 [MH+]
Example 139
2-[ 1 -(4-Cyano-benzyl)- lH-indol-3-yl]-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 518 [MH+] 45
Example 140
3-Oxo-4-piperidin-4-yl-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 487 [MH+]
Example 141
4-(3-Amino-propyl)-2-(l-ethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 405 [MH+]
Example 142
4-(3-Amino-propyl)-2-(l-diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 490 [MH+]
Example 143
4-(3-Amino-propyl)-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro-quinoxaline- 6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 492 [MH+] 46
Example 144
4-(3-Amino-propyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 461 [MH+]
Example 145
4-[2-(2-Amino-ethoxy)-ethyl]-2-(l-ethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 435 [MH+]
Example 146
4-[2-(2-Amino-ethoxy)-ethyl]-2-(l-diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 520 [MH+]
Example 147
4-[2-(2-Amino-ethoxy)-ethyl]-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 522 [MH+] 47
Example 148
4-[2-(2-Amino-ethoxy)-ethyl]-3-oxo-2-[ l-(tetrahydro-furan-2-y Imethyl)- lH-indol-3-yl]- 3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 491 [MH+]
Example 149
4-(5- Amino-pentyl)-2-( 1 -ethyl- 1 H-indol-3-yl)-3-oxo-3 ,4-dihydro-quinoxaline-6-carboxy lie acid methyl ester trifluoroacetic acid salt
APCI-MS: 433 [MH+]
Example 150
4-(5- Amino-pentyl)-2-( 1 -diethylcarbamoylmethyl- 1 H-indol-3-yl)-3-oxo-3 ,4-dihy dro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 518 [MH+]
Example 151
4-(5-Amino-pentyl)-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro-quinoxaline- 6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 520 [MH+] 48
Example 152
4-(5-Amino-ρentyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
APCI-MS: 489 [MH+]
Example 153
3-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-6-methyl-lH-quinoxalin-2-one acetic acid salt
APCI-MS: 362 [MH+J
Example 154
1 -(5- Amino-penty l)-3-(lH-indol-3-yl)-6,7-dimethyl-lH-quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: 375 [MH+]
Example 155
l-[2-(2-Amino-ethoxy)-ethyl]-3-[l-(3-methoxy-benzyl)-lH-indol-3-yl]-lH- benzo[g]quinoxalin-2-one trifluoroacetic acid salt
APCI-MS: m/z 519 [MH+]

Claims

49CLAIMS
1. An optionally substituted and/or annulated compound of formula (I):
(I)
Figure imgf000051_0001
and salts thereof.
2. A compound according to claim 1 , of formula (LI):
(ll)
Figure imgf000051_0002
wherein:
Rl is H, 2-amino-l -methyl-ethyl, 2-methylamino-ethyl, 2-amino-4-methyl-pentyl, piperidin-3-ylmethyl, piperidin-4-yl, 3-aminopropyl, 2-(2-amino-ethoxy)-ethyl or 5-amino-pentyl,
R2 is H, halogen, or carboxy -╬▓alkyl,
R3 is C1-6 alkyl, N,N-diethylacetamid-2-yl, 4-cyanobenzyl, tetrahydro-furan-2-ylmethyl, 3-amino-propyl or 3-amino-butyl, 50
R4 and R5 are each independently H, halogen, benzyloxy or carboxyQ-╬▓alkyl,
and salts thereof.
3. An optionally substituted and/or annulated compound according to claim 2, comprising
i) 3-[l-(3-Amino-propyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one or ii) 3-[ 1 -(4- Amino-butyl)- 1 H-indol-3-yl]-7 -phenyl- lH-quinoxalin-2-one
and salts thereof.
4. The compounds:
l-(3-Amino-propyl)-3-(3-oxo-6-phenyl-3,4-dihydro-quinoxalin-2-yl)-lH-indole-5- carboxylic acid methyl ester acetic acid salt,
3-[ 1 -(3-Amino-propyl)-6-benzyloxy- lH-indol-3-yl]-7 -phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3- Amino-propyl)-5-benzyloxy- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3- Amino-propyl)-5-bromo- 1 H-indol-3-y l]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(4-Amino-butyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-ρropyl)-lH-indol-3-yl]-7-ρhenyl-lH-quinoxalin-2-one acetic acid salt, 51
and their free bases and other pharmaceutically acceptable salts thereof.
5. An optionally substituted and/or annulated compound of formula (HI)
Figure imgf000053_0002
(IH)
Figure imgf000053_0001
and salts thereof.
6. A compound according to claim 5, of formula (IV)
m O^ ΓÇ₧.N ^^ .R2
Ph,
Figure imgf000053_0003
R3 " πo (i )
wherein:
Rl is H, 2-amino-l -methyl-ethyl, 2-methylamino-ethyl, 2-amino-4-methyl-pentyl, piperidin-3-ylmethyl, piperidin-4-yl, 3-aminopropyl, 2-(2-amino-ethoxy)-ethyl or 5-amino-pentyl,
R2 is H, halogen, or carboxyCi-όalkyl,
R3 is H, halogen, phenyl or carboxy .6alkyl,
R4 is C1-6 alkyl, N,N-diethylacetamid-2-yl, 4-cyanobenzyl, tetrahydro-furan-2-y Imethyl, 52
3-amino-propyl or 3-amino-butyl,
and salts thereof.
7. The compounds:
3-( 1 -Ethyl- 1 H-indol-3-y 1)- 1 -piperidin-3-ylmethy 1- 1 H-quinoxalin-2-one trifluoroacetic acid salt,
3-[l-(3-Amino-propyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
1 -(6- Amino-hexyl)-6,7-dichloro-3-[ 1 -(3-methoxy-benzyl)- 1 H-indol-3-yl]- 1 H-quinoxalin- 2-one trifluoroacetic acid salt,
1 -(5- Amino-pentyl)-6,7-dichloro-3-[ 1 -(3-methoxy-benzyl)- 1 H-indol-3-yl]- 1 H-quinoxalin- 2-one trifluoroacetic acid salt,
1 -(3-Hydroxymethyl-benzyl)-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one,
l-[3-(4-Hydroxy-phenyl)^ ropyl]-3-(lH-indol-3-yl)-6,7-dimethyl-lH-quinoxalin-2-one,
3-( 1 H-Indol-3-yl)-6,7-dimethyl- 1 -(2-piperazin- 1 -yl-ethyl)- 1 H-quinoxalin-2-onebis trifluoroacetic acid salt,
1 -[2-(2-Amino-ethoxy)-ethyl]-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt,
1 -(2- Amino-ethyl)-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt, 53
1 -(2- Amino- 1 -methyl-ethyl)-3-( 1 H-indol-3-yl)-6,7-dimethy 1- 1 H-quinoxalin-2-one trifluoroacetic acid salt,
1 -(4- Amino-cyclohexyl)-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt,
3-[ 1 -(3-Amino-propyl)-6-nitro- lH-indol-3-yl]- 1 H-pyrido[2,3-b]pyrazin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-6-nitro- 1 H-indol-3-yl]-6,7-dimethyl- 1 H-quinoxalin-2-one acetic acid salt,
2-[l-(3-Amino-propyl)-6-nitro-lH-indol-3-yl]-4H-pyrido[3,4-b]pyrazin-3-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-6-nitro- 1 H-indol-3-yl]-7-trifluoromethyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-lH-pyrido[2,3-b]pyrazin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-7-ethyl- 1 H-indol-3-yl]-6,7 -dimethyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-7-ethyl- 1 H-indol-3-yl]-6,7-dichloro- 1 H-quinoxalin-2-one acetic acid salt,
2-[l-(3-Amino-propyl)-7-ethyl-lH-indol-3-yl]-4H-pyrido[3,4-b]pyrazin-3-one acetic acid salt, 54
2-[l-(3-Amino-propyl)-7-ethyl- lH-indol-3-yl]-4H-pyrido[3,4-b]pyrazin-3-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-7-ethyl- 1 H-indol-3-yl ]-7-trifluoromethyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-7 -ethyl- lH-indol-3-yl]-7-nitro- 1 H-quinoxalin-2-one acetic acid salt,
3-[5-(3-Aminomethyl-benzyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-7-phenyl-lH-quinoxalin- 2-one acetic acid salt,
3-[5-(3-Amino-propyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-5-dibenzylamino- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-2-(4-chloro-phenyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3- Amino-propyl)-2-methyl- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-6-nitro-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3- Amino-propyl)-5-methoxy- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt, 55
3-[5-(3-Aminomethyl-benzyl)-5H-[l,3]dioxolo[4,5-fjindol-7-yl]-5-phenyl-lH-quinoxalin- 2-one acetic acid salt,
3-[5-(3-Amino-propyl)-5H-[l,3]dioxolo[4,5-f]indol-7-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3- Amino-propyl)-5-dibenzylamino- 1 H-indol-3-yl]-5-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-2-methyl-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
l-(3-Amino-propyl)-3-(3-oxo-8-phenyl-3,4-dihydro-quinoxalin-2-yl)-lH-indole-5- carboxylic acid methyl ester acetic acid salt,
3-[l-(3-Amino-propyl)-6-nitro-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-5-methoxy-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3- Amino-propyl)-2-ethyl- 1 H-indol-3-yl ]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(4-Amino-butyl)-2-benzyl-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(6-Aminomethyl-pyridin-2-ylmethyl)- 1 H-indol-3-yl]-7-phenyl- 1 H-quinoxalin-2-one acetic acid salt, 56
3-[ 1 -(4-Aminomethyl-benzyl)- 1 H-indol-3-yl]-7 -phenyl- 1 H-quinoxalin-2-one acetic acid salt,
3-[l-(3-Aminomethyl-benzyl)-lH-indol-3-yl]-7-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-6-benzyloxy-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-5-benzyloxy-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt,
3-[ 1 -(3-Amino-propyl)-5-bromo- lH-indol-3-yl]-5-phenyl- lH-quinoxalin-2-one acetic acid salt,
3-[l-(3-Amino-propyl)-2-ethyl-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
3-[l-(4-Amino-butyl)-2-benzyl-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
3-[l-(4-Aminomethyl-benzyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
3-[l-(3-Aminomethyl-benzyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
3-[l-(4-Amino-butyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt
3-[l-(3-Amino-propyl)-lH-indol-3-yl]-5-phenyl-lH-quinoxalin-2-one acetic acid salt 57
1 -(2- Amino- 1 -methyl-ethyl)-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{ 3-[4-(2- Amino- l-methyl-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -yl } -N,N- diethyl-acetamide trifluoroacetic acid salt
4-{3-[4-(2-Amino-l-methyl-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-ylmethyl}- benzonitrile trifluoroacetic acid salt
1 -(2- Amino- 1 -methyl-ethyl)-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
3-( 1 -Ethyl- 1 H-indol-3-yl)- 1 -(2-methylamino-ethyl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
N,N-Diethyl-2-{3-[4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- yl} -acetamide trifluoroacetic acid salt
4- { 3-[4-(2-Methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -ylmethyl } - benzonitrile trifluoroacetic acid salt
1 -(2-Methylamino-ethyl)-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
1 -(2- Amino-4-methyl-pentyl)-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{ 3-[4-(2-Amino-4-methyl-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -yl } -N,N- diethyl-acetamide trifluoroacetic acid salt 58
4-{ 3-[4-(2-Amino-4-methyl-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 - ylmethyl }-benzonitrile trifluoroacetic acid salt
1 -(2- Amino-4-methyl-pentyl)-3-[ 1 -(tetrahydro-furan-2-y Imethyl)- 1 H-indol-3-yl ]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
3-( 1 -Ethyl- 1 H-indol-3-yl)- 1 -piperidin-3-ylmethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
N,N-Diethyl-2-[3-(3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]- acetamide trifluoroacetic acid salt
4-[3-(3-Oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l-ylmethyl]- benzonitrile trifluoroacetic acid salt
1 -Piperidin-3-ylmethyl-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- lH-indol-3-yl]- 1 H-quinoxalin- 2-one trifluoroacetic acid salt
3-( 1 -Ethyl- 1 H-indol-3-yl)- 1 -piperidin-4-yl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
N,N-Diethyl-2-[3-(3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]- acetamide trifluoroacetic acid salt
4-[3-(3-Oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol- 1 -ylmethylj-benzonitrile trifluoroacetic acid salt
1 -Piperidin-4-yl-3-[ 1 -(tetrahydro-furan-2-y Imethyl)- 1 H-indol-3-yl ]- 1 H-quinoxalin-2-one trifluoroacetic acid salt 59
1 -(3- Amino-propyl)-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[4-(3-Amino-propyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-yl}-N,N-diethyl- acetamide trifluoroacetic acid salt
4- { 3-[4-(3- Amino-propy l)-3 -oxo-3, 4-dihydro-quinoxalin-2-yl] -indol- 1 -ylmethyl } - benzonitrile trifluoroacetic acid salt
l-(3-Amino-propyl)-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH-quinoxalin-2- one trifluoroacetic acid salt
1 -[2-(2-Amino-ethoxy)-ethyl]-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-(3- { 4-[2-(2- Amino-ethoxy)-ethyl]-3-oxo-3 ,4-dihydro-quinoxalin-2-yl } -indol- 1 -y 1)-N,N- diethyl-acetamide trifluoroacetic acid salt
4-(3- { 4-[2-(2-Amino-ethoxy)-ethyl]-3-oxo-3,4-dihydro-quinoxalin-2-yl } -indol- 1 - ylmethyl)-benzonitrile trifluoroacetic acid salt
1 -[2-(2-Amino-ethoxy)-ethyl]-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
1 -(5- Amino-pentyl)-3-( 1 -ethyl- 1 H-indol-3-y 1)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[4-(5-Amino-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-yl}-N,N-diethyl- acetamide trifluoroacetic acid salt 60
4-{3-[4-(5-Amino-pentyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-ylmethyl}- benzonitrile trifluoroacetic acid salt
l-(5-Amino-pentyl)-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH-quinoxalin-2- one trifluoroacetic acid salt
1 -(2- Amino- 1 -methy l-ethyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-y 1)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[4-(2-Amino-l-methyl-ethyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- l-yl}-N,N-diethyl-acetamide trifluoroacetic acid salt
4-{3-[4-(2-Amino-l-methyl-ethyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 -ylmethyl }-benzonitrile trifluoroacetic acid salt
1 -(2- Amino- 1 -methyl-ethy l)-6,7-dichloro-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3- yl]-lH-quinoxalin-2-one trifluoroacetic acid salt
6,7-Dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 -(2-methylamino-ethyl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[6,7-Dichloro-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- yl}-N,N-diethyl-acetamide trifluoroacetic acid salt
4-{3-[6,7-Dichloro-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- ylmethylj-benzonitrile trifluoroacetic acid salt
6,7-Dichloro- 1 -(2-methylamino-ethyl)-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- lH-quinoxalin-2-one trifluoroacetic acid salt 61
1 -(2- Amino-4-methyl-pentyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[4-(2-Amino-4-methyl-pentyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]- indol- 1 -yl } -N,N-diethyl-acetamide trifluoroacetic acid salt
4-{3-[4-(2-Amino-4-methyl-pentyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]- indol-1 -ylmethyl }-benzonitrile trifluoroacetic acid salt
l-(2-Amino-4-methyl-pentyl)-6,7-dichloro-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3- yl]-lH-quinoxalin-2-one trifluoroacetic acid salt
6,7-Dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 -piperidin-3-y Imethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-[3-(6,7-Dichloro-3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]- N,N-diethyl-acetamide trifluoroacetic acid salt
4-[3-(6,7-Dichloro-3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro-quinoxalin-2-yl)-indol-l- ylmethyl]-benzonitrile trifluoroacetic acid salt
6,7-Dichloro- 1 -piperidin-3-ylmethyl-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl ]- lH-quinoxalin-2-one trifluoroacetic acid salt
6,7-Dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 -piperidin-4-yl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-[3-(6,7-Dichloro-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-yl]-N,N- diethyl-acetamide trifluoroacetic acid salt 62
4-[3-(6,7-Dichloro-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxalin-2-yl)-indol-l-ylmethyl]- benzonitrile trifluoroacetic acid salt
6,7-Dichloro-l-piperidin-4-yl-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH- quinoxalin-2-one trifluoroacetic acid salt
1 -(3- Amino-propyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[4-(3-Amino-propyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-yl}- N,N-diethyl-acetamide trifluoroacetic acid salt
4-{3-[4-(3-Amino-propyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l- ylmethylj-benzonitrile trifluoroacetic acid salt
1 -(3-Amino-propyl)-6,7-dichloro-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-yl]- 1 H- quinoxalin-2-one trifluoroacetic acid salt
1 -[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-( 1 -ethyl- lH-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-(3- { 4-[2-(2- Amino-ethoxy)-ethyl]-6,7-dichloro-3-oxo-3 ,4-dihydro-quinoxalin-2-y 1 } - indol- l-yl)-N,N-diethyl-acetamide trifluoroacetic acid salt
4-(3-{4-[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl}- indol- l-ylmethyl)-benzonitrile trifluoroacetic acid salt
1 -[2-(2-Amino-ethoxy)-ethyl]-6,7-dichloro-3-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3- yl]-lH-quinoxalin-2-one trifluoroacetic acid salt 63
1 -(5- Amino-pentyl)-6,7-dichloro-3-( 1 -ethyl- 1 H-indol-3-yl)- 1 H-quinoxalin-2-one trifluoroacetic acid salt
2-{3-[4-(5-Amino-pentyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol-l-yl}- N,N-diethyl-acetamide trifluoroacetic acid salt
4- { 3-[4-(5-Amino-pentyl)-6,7-dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl]-indol- 1 - ylmethyl }-benzonitrile trifluoroacetic acid salt
l-(5-Amino-pentyl)-6,7-dichloro-3-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-lH- quinoxalin-2-one trifluoroacetic acid salt
4-(2- Amino- 1 -methyl-ethyl)-2-( 1 -ethyl- 1 H-indol-3-y l)-3-oxo-3 ,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
4-(2- Amino- 1 -methyl-ethyl)-2-( 1 -diethylcarbamoylmethyl- 1 H-indol-3-y l)-3-oxo-3 ,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(2- Amino- 1 -methyl-ethyl)-2-[ 1 -(4-cyano-benzyl)- 1 H-indol-3-yl]-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(2- Amino- 1 -methyl-ethyl)-3-oxo-2-[ 1 -(tetrahydro-furan-2-ylmethyl)- 1 H-indol-3-y l]-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
2-( 1 -Ethyl- lH-indol-3-yl)-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
2-( 1 -Diethylcarbamoylmethyl- 1 H-indol-3-yl)-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt 64
2-[l-(4-Cyano-benzyl)-lH-indol-3-yl]-4-(2-methylamino-ethyl)-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(2-Methylamino-ethyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4- 5 dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(2-Amino-4-methyl-pentyl)-2-( 1 -ethyl- 1 H-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
l o 4-(2- Amino-4-methyl-pentyl)-2-( 1 -diethylcarbamoylmethyl- 1 H-indol-3-y l)-3-oxo-3 ,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(2-Amino-4-methyl-pentyl)-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
15
4-(2-Amino-4-methyl-pentyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-ylj- 3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
2-( 1 -Ethyl- 1 H-indol-3-yl)-3-oxo-4-piperidin-3-ylmethyl-3 ,4-dihydro-quinoxaline-6- 20 carboxylic acid methyl ester trifluoroacetic acid salt
2-(l-Diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
25 2-[l-(4-Cyano-benzyl)-lH-indol-3-yl]-3-oxo-4-piperidin-3-ylmethyl-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
3-Oxo-4-piperidin-3-ylmethyl-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
30 65
2-( 1 -Ethyl- 1 H-indol-3-yl)-3-oxo-4-piperidin-4-yl-3 ,4-dihydro-quinoxaline-6-carboxy lie acid methyl ester trifluoroacetic acid salt
2-(l-Diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-4-piperidin-4-yl-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
2-[l-(4-Cyano-benzyl)-lH-indol-3-yl]-3-oxo-4-piperidin-4-yl-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
3-Oxo-4-piperidin-4-yl-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(3-Amino-propyl)-2-(l-ethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(3- Amino-propyl)-2-( 1 -diethylcarbamoylmethyl- 1 H-indol-3-yl)-3-oxo-3 ,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(3-Amino-propyl)-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro-quinoxaline- 6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(3-Amino-propyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-[2-(2-Amino-ethoxy)-ethyl]-2-(l-ethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6- carboxylic acid methyl ester trifluoroacetic acid salt
4-[2-(2-Amino-ethoxy)-ethyl]-2-(l-diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-3,4- dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt 66
4-[2-(2-Amino-ethoxy)-ethyl]-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-[2-(2-Amino-ethoxy)-ethyl]-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]- 3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(5-Amino-pentyl)-2-(l-ethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro-quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(5-Amino-pentyl)-2-(l-diethylcarbamoylmethyl-lH-indol-3-yl)-3-oxo-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(5-Amino-pentyl)-2-[l-(4-cyano-benzyl)-lH-indol-3-yl]-3-oxo-3,4-dihydro-quinoxaline- 6-carboxylic acid methyl ester trifluoroacetic acid salt
4-(5-Amino-pentyl)-3-oxo-2-[l-(tetrahydro-furan-2-ylmethyl)-lH-indol-3-yl]-3,4-dihydro- quinoxaline-6-carboxylic acid methyl ester trifluoroacetic acid salt
3-[ 1 -(3- Amino-propyl)-7-ethyl- 1 H-indol-3-yl ]-6-methyl- 1 H-quinoxalin-2-one acetic acid salt
1 -(5- Amino-penty l)-3-( 1 H-indol-3-yl)-6,7-dimethyl- 1 H-quinoxalin-2-one trifluoroacetic acid salt
l-[2-(2-Amino-ethoxy)-ethyl]-3-[l-(3-methoxy-benzyl)-lH-indol-3-yl]-lH- benzo[g]quinoxalin-2-one trifluoroacetic acid salt,
and their free bases and other pharmaceutically acceptable salts thereof 67
8. A pharmaceutical composition wherein the active ingredient is a compound according to any one of claims 1 to 7 together with a pharmaceutically acceptable adjuvant, diluent or carrier.
9. A compound according to any one of claims 1 to 7, for use in medical therapy.
10. The compound according to claim 9, wherein the medical therapy is the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS- degenerative disorders.
11. Use of a compound according to any one of claims 1 to 7 in the manufacture of a medicament for the treatment of inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders.
12. A method for treatment of an inflammatory, immunological, bronchopulmonary, cardiovascular, oncological or CNS-degenerative disorders, wherein a therapeutically effective amount of a compound according to any one of claims 1 to 7 is administered to a mammal in need of such treatment.
PCT/SE1999/000276 1998-03-13 1999-02-26 New compounds WO1999046260A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU28638/99A AU2863899A (en) 1998-03-13 1999-02-26 New compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9800836-0 1998-03-13
SE9800836A SE9800836D0 (en) 1998-03-13 1998-03-13 New Compounds

Publications (1)

Publication Number Publication Date
WO1999046260A1 true WO1999046260A1 (en) 1999-09-16

Family

ID=20410540

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1999/000276 WO1999046260A1 (en) 1998-03-13 1999-02-26 New compounds

Country Status (3)

Country Link
AU (1) AU2863899A (en)
SE (1) SE9800836D0 (en)
WO (1) WO1999046260A1 (en)

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004052854A2 (en) * 2002-12-10 2004-06-24 Wyeth Aryl, aryloxy, and alkyloxy substituted 1h-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1)
WO2005051957A1 (en) * 2003-11-21 2005-06-09 Bayer Pharmaceuticals Corporation Indolyl-thieno`3,4-b!pyrazin-3-one derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
WO2005067932A1 (en) * 2004-01-06 2005-07-28 Janssen Pharmaceutica, N.V. (3-oxo-3, 4-dihydro-quinoxalin-2-yl-amino) -benzamide derivatives and related compound as glycogen phosphorylase inhibitors for the treatment of diabetes and obesity
US7056943B2 (en) 2002-12-10 2006-06-06 Wyeth Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7074817B2 (en) 2001-06-20 2006-07-11 Wyeth Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7078429B2 (en) 2002-12-10 2006-07-18 Wyeth Substituted 3-carbonyl-1H-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7101903B2 (en) 2002-12-10 2006-09-05 Wyeth Substituted dihydropyrano indole-3,4-dione derivatives as inhibitiors of plasminogen activator inhibitor-1 (PAI-1)
US7141592B2 (en) 2003-09-25 2006-11-28 Wyeth Substituted oxadiazolidinediones
US7163954B2 (en) 2003-09-25 2007-01-16 Wyeth Substituted naphthyl benzothiophene acids
US7265148B2 (en) 2003-09-25 2007-09-04 Wyeth Substituted pyrrole-indoles
US7268159B2 (en) 2003-09-25 2007-09-11 Wyeth Substituted indoles
US7332521B2 (en) 2003-09-25 2008-02-19 Wyeth Substituted indoles
US7342039B2 (en) 2003-09-25 2008-03-11 Wyeth Substituted indole oximes
US7348351B2 (en) 2002-12-10 2008-03-25 Wyeth Substituted 3-alkyl and 3-arylalkyl 1H-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7351730B2 (en) 2001-06-20 2008-04-01 Wyeth Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7351726B2 (en) 2003-09-25 2008-04-01 Wyeth Substituted oxadiazolidinediones
US7411083B2 (en) 2003-09-25 2008-08-12 Wyeth Substituted acetic acid derivatives
US7420083B2 (en) 2003-09-25 2008-09-02 Wyeth Substituted aryloximes
US7442805B2 (en) 2003-09-25 2008-10-28 Wyeth Substituted sulfonamide-indoles
US7446201B2 (en) 2003-09-25 2008-11-04 Wyeth Substituted heteroaryl benzofuran acids
WO2008148867A2 (en) 2007-06-08 2008-12-11 Novartis Ag Quinoxaline derivatives as inhibitors of the tyrosine kinase activity of janus kinases
US7582773B2 (en) 2003-09-25 2009-09-01 Wyeth Substituted phenyl indoles
WO2009109341A1 (en) 2008-03-05 2009-09-11 Merck Patent Gmbh Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
US7683091B2 (en) 2005-08-17 2010-03-23 Wyeth Substituted indoles and methods of their use
WO2010053757A1 (en) * 2008-10-29 2010-05-14 Gilead Palo Alto, Inc. 2 -oxoquinoxalin blockers of the late sodium channel
US7754747B2 (en) 2004-08-23 2010-07-13 Wyeth Llc Oxazolo-naphthyl acids
US20100216726A1 (en) * 2007-08-31 2010-08-26 Purdue Pharma L.P. Substituted-Quinoxaline-Type Piperidine Compounds and the Uses Thereof
WO2012085648A1 (en) 2010-12-22 2012-06-28 Purdue Pharma L.P. Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof
EP2537844A1 (en) 2008-07-21 2012-12-26 Purdue Pharma L.P. Substituted-quinoxaline-type bridged-piperidine compounds and the uses thereof
WO2013080036A1 (en) 2011-12-01 2013-06-06 Purdue Pharma L.P. Azetidine-substituted quinoxaline-type piperidine compounds and uses thereof
WO2014020405A1 (en) 2012-07-30 2014-02-06 Purdue Pharma L.P. Cyclic urea- or lactam-substituted quinoxaline-type piperidine compounds and the uses thereof
US8664379B2 (en) 2008-10-30 2014-03-04 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
WO2014102589A1 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Quinazolin-4(3h)-one-type piperidine compounds and uses thereof
WO2014102588A2 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Indole and indoline-type piperidine compounds and uses thereof
WO2014102594A2 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Substituted benzimidazole-type piperidine compounds and uses thereof
WO2014102592A2 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Oxime/substituted quinoxaline-type piperidine compounds and uses thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114524805B (en) * 2022-03-10 2023-01-24 浙江树人学院(浙江树人大学) Application of solid acid catalysis multi-component reaction in preparation of fluorine-containing medicine

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998013368A1 (en) * 1996-09-25 1998-04-02 Astra Aktiebolag (Publ) New pharmaceutically active compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998013368A1 (en) * 1996-09-25 1998-04-02 Astra Aktiebolag (Publ) New pharmaceutically active compounds

Cited By (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7074817B2 (en) 2001-06-20 2006-07-11 Wyeth Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7351730B2 (en) 2001-06-20 2008-04-01 Wyeth Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7368471B2 (en) 2001-06-20 2008-05-06 Wyeth Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7629377B2 (en) 2001-06-20 2009-12-08 Wyeth Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7101903B2 (en) 2002-12-10 2006-09-05 Wyeth Substituted dihydropyrano indole-3,4-dione derivatives as inhibitiors of plasminogen activator inhibitor-1 (PAI-1)
US7056943B2 (en) 2002-12-10 2006-06-06 Wyeth Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
JP2006510673A (en) * 2002-12-10 2006-03-30 ワイス Aryl, aryloxy and alkyloxy substituted 1H-indol-3-ylglyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor 1 (PAI-1)
US7078429B2 (en) 2002-12-10 2006-07-18 Wyeth Substituted 3-carbonyl-1H-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7348351B2 (en) 2002-12-10 2008-03-25 Wyeth Substituted 3-alkyl and 3-arylalkyl 1H-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7566791B2 (en) 2002-12-10 2009-07-28 Wyeth Substituted 3-carbonyl-1h-indol-1yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7160918B2 (en) 2002-12-10 2007-01-09 Hassan Mahmoud Elokdah Substituted indole oxo-acetyl amino acetic acid derivatives as inhibitors of plasminogen activator inhibitor (PAI-1)
WO2004052854A2 (en) * 2002-12-10 2004-06-24 Wyeth Aryl, aryloxy, and alkyloxy substituted 1h-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1)
US7459478B2 (en) 2002-12-10 2008-12-02 Wyeth Substituted dihydropyrano indole-3,4-dione derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7259182B2 (en) 2002-12-10 2007-08-21 Wyeth Aryl, aryloxy, and aklyloxy substituted 1H-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
US7674818B2 (en) 2002-12-10 2010-03-09 Wyeth Llc Aryl, aryloxy, alkyloxy substituted 1H-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
WO2004052854A3 (en) * 2002-12-10 2004-08-05 Wyeth Corp Aryl, aryloxy, and alkyloxy substituted 1h-indol-3-yl glyoxylic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1)
US7332521B2 (en) 2003-09-25 2008-02-19 Wyeth Substituted indoles
US7446201B2 (en) 2003-09-25 2008-11-04 Wyeth Substituted heteroaryl benzofuran acids
US7582773B2 (en) 2003-09-25 2009-09-01 Wyeth Substituted phenyl indoles
US7268159B2 (en) 2003-09-25 2007-09-11 Wyeth Substituted indoles
US7351726B2 (en) 2003-09-25 2008-04-01 Wyeth Substituted oxadiazolidinediones
US7265148B2 (en) 2003-09-25 2007-09-04 Wyeth Substituted pyrrole-indoles
US7411083B2 (en) 2003-09-25 2008-08-12 Wyeth Substituted acetic acid derivatives
US7420083B2 (en) 2003-09-25 2008-09-02 Wyeth Substituted aryloximes
US7442805B2 (en) 2003-09-25 2008-10-28 Wyeth Substituted sulfonamide-indoles
US7342039B2 (en) 2003-09-25 2008-03-11 Wyeth Substituted indole oximes
US7141592B2 (en) 2003-09-25 2006-11-28 Wyeth Substituted oxadiazolidinediones
US7803835B2 (en) 2003-09-25 2010-09-28 Wyeth Llc Substituted acetic acid derivatives
US7163954B2 (en) 2003-09-25 2007-01-16 Wyeth Substituted naphthyl benzothiophene acids
JP2007512331A (en) * 2003-11-21 2007-05-17 バイエル・フアーマシユーチカルズ・コーポレーシヨン Indolyl-thieno'3,4-B useful for the treatment of hyperproliferative diseases and diseases associated with angiogenesis! Pyrazin-3-one derivatives
WO2005051957A1 (en) * 2003-11-21 2005-06-09 Bayer Pharmaceuticals Corporation Indolyl-thieno`3,4-b!pyrazin-3-one derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
WO2005067932A1 (en) * 2004-01-06 2005-07-28 Janssen Pharmaceutica, N.V. (3-oxo-3, 4-dihydro-quinoxalin-2-yl-amino) -benzamide derivatives and related compound as glycogen phosphorylase inhibitors for the treatment of diabetes and obesity
US7754747B2 (en) 2004-08-23 2010-07-13 Wyeth Llc Oxazolo-naphthyl acids
US7683091B2 (en) 2005-08-17 2010-03-23 Wyeth Substituted indoles and methods of their use
JP2010529088A (en) * 2007-06-08 2010-08-26 ノバルティス アーゲー Quinoxaline derivatives as inhibitors of Janus kinase tyrosine kinase activity
WO2008148867A3 (en) * 2007-06-08 2009-04-09 Novartis Ag Quinoxaline derivatives as inhibitors of the tyrosine kinase activity of janus kinases
US8193189B2 (en) 2007-06-08 2012-06-05 Novartis Ag Quinoxaline derivatives as tyrosine kinase activity inhibitors
WO2008148867A2 (en) 2007-06-08 2008-12-11 Novartis Ag Quinoxaline derivatives as inhibitors of the tyrosine kinase activity of janus kinases
EP2433936A1 (en) 2007-08-31 2012-03-28 Purdue Pharma LP Substituted-quinoxaline-type-piperidine compounds and the uses thereof
EP3101018A1 (en) 2007-08-31 2016-12-07 Purdue Pharma L.P. Substituted-quinoxaline-type-piperidine compounds and the uses thereof
JP2010537969A (en) * 2007-08-31 2010-12-09 パーデュー、ファーマ、リミテッド、パートナーシップ Substituted quinoxaline-type piperidine compounds and uses thereof
EP2433935A1 (en) 2007-08-31 2012-03-28 Purdue Pharma LP Substituted-quinoxaline-type-piperidine compounds and the uses thereof
EP2433937A1 (en) 2007-08-31 2012-03-28 Purdue Pharma LP Substituted-quinoxaline-type-piperidine compounds and the uses thereof
US8846929B2 (en) 2007-08-31 2014-09-30 Purdue Pharma L.P. Substituted-quinoxaline-type piperidine compounds and the uses thereof
US9278967B2 (en) 2007-08-31 2016-03-08 Purdue Pharma L.P. Substituted-quinoxaline-type piperidine compounds and the uses thereof
US20100216726A1 (en) * 2007-08-31 2010-08-26 Purdue Pharma L.P. Substituted-Quinoxaline-Type Piperidine Compounds and the Uses Thereof
EP3564240A1 (en) 2007-08-31 2019-11-06 Purdue Pharma L.P. Piperidine intermediates
US9527840B2 (en) 2007-08-31 2016-12-27 Purdue Pharma L.P. Substituted-quinoxaline-type piperidine compounds and the uses thereof
WO2009109341A1 (en) 2008-03-05 2009-09-11 Merck Patent Gmbh Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
US8178556B2 (en) 2008-03-05 2012-05-15 Merck Patent Gesellschaft Mit Beschraenkter Haftung Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
US8609689B2 (en) 2008-03-05 2013-12-17 Merck Patent Gmbh Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
US8642617B2 (en) 2008-03-05 2014-02-04 Merck Patent Gmbh Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
EA020372B1 (en) * 2008-03-05 2014-10-30 Мерк Патент Гмбх Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
US9145408B2 (en) 2008-07-21 2015-09-29 Purdue Pharma L.P. Substituted-quinoxaline-type bridged-piperidine compounds as ORL-1 modulators
US8476271B2 (en) 2008-07-21 2013-07-02 Purdue Pharma, L.P. Substituted-quinoxaline-type bridged-piperidine compounds as ORL-1 modulators
US11111246B2 (en) 2008-07-21 2021-09-07 Purdue Pharma L.P. Pharmaceutical salts of substituted-quinoxaline-type bridged-piperidine compounds
US9890164B2 (en) 2008-07-21 2018-02-13 Purdue Pharma, L.P. Substituted-quinoxaline-type bridged-piperidine compounds as ORL-1 modulators
EP2537844A1 (en) 2008-07-21 2012-12-26 Purdue Pharma L.P. Substituted-quinoxaline-type bridged-piperidine compounds and the uses thereof
US8912190B2 (en) 2008-10-29 2014-12-16 Gilead Sciences, Inc. Substituted heterocyclic compounds
WO2010053757A1 (en) * 2008-10-29 2010-05-14 Gilead Palo Alto, Inc. 2 -oxoquinoxalin blockers of the late sodium channel
US8664379B2 (en) 2008-10-30 2014-03-04 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
US8952007B2 (en) 2008-10-30 2015-02-10 Gilead Sciences, Inc. Fused heterocyclic compounds as ion channel modulators
WO2012085648A1 (en) 2010-12-22 2012-06-28 Purdue Pharma L.P. Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof
US9598447B2 (en) 2010-12-22 2017-03-21 Purdue Pharma L.P. Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof
WO2013080036A1 (en) 2011-12-01 2013-06-06 Purdue Pharma L.P. Azetidine-substituted quinoxaline-type piperidine compounds and uses thereof
US9290488B2 (en) 2011-12-01 2016-03-22 Purdue Pharma L.P. Azetidine-substituted quinoxalines as opioid receptor like-1 modulators
WO2014020405A1 (en) 2012-07-30 2014-02-06 Purdue Pharma L.P. Cyclic urea- or lactam-substituted quinoxaline-type piperidine compounds and the uses thereof
US9085561B2 (en) 2012-07-30 2015-07-21 Purdue Pharma L.P. Cyclic urea- or lactam-substituted quinoxaline-type piperidines as ORL-1 modulators
US9090618B2 (en) 2012-12-27 2015-07-28 Purdue Pharma L.P. Substituted benzimidazole-type piperidine compounds and uses thereof
US9040533B2 (en) 2012-12-27 2015-05-26 Purdue Pharma L.P. Oxime-substituted-quinoxaline-type piperidine compounds as ORL-1 modulators
WO2014102589A1 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Quinazolin-4(3h)-one-type piperidine compounds and uses thereof
US9598411B2 (en) 2012-12-27 2017-03-21 Purdue Pharma L.P. Substituted benzimidazole-type piperidine compounds and uses thereof
WO2014102592A2 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Oxime/substituted quinoxaline-type piperidine compounds and uses thereof
US9951038B2 (en) 2012-12-27 2018-04-24 Purdue Pharma L.P. Quinazolin-4(3H)-one-type piperidine compounds and uses thereof
US9963458B2 (en) 2012-12-27 2018-05-08 Purdue Pharma L.P. Indole and indoline-type piperidine compounds and uses thereof
WO2014102594A2 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Substituted benzimidazole-type piperidine compounds and uses thereof
WO2014102588A2 (en) 2012-12-27 2014-07-03 Purdue Pharma L.P. Indole and indoline-type piperidine compounds and uses thereof

Also Published As

Publication number Publication date
SE9800836D0 (en) 1998-03-13
AU2863899A (en) 1999-09-27

Similar Documents

Publication Publication Date Title
WO1999046260A1 (en) New compounds
US6271231B1 (en) Pharmaceutically active compounds
EP2493895B1 (en) N-containing heteroaryl derivatives as jak3 kinase inhibitors
KR20010113829A (en) New Pharmaceutically Active Compounds
EP3134402A1 (en) 4-amino-imidazoquinoline compounds
AU2005315783A1 (en) Trycyclic heterocycles, their manufacture and use as pharmaceutical agents
SK5462003A3 (en) Indolylmaleimide derivatives, method for the preparation thereof and pharmaceutical composition comprising same
EP1495016A2 (en) Heterocyclic compounds and their use as modulators of p38 map kinase
EP1689739B1 (en) Azole-based kinase inhibitors
JP2003519140A (en) 2- (1H-indol-3-yl) -2-oxo-acetamide having antitumor activity
EP0925296A1 (en) New pharmaceutically active compounds
EP1042317B1 (en) Indole derivatives as PKC-inhiboitors
HU207078B (en) Process for producing lactam derivatives and pharmaceutical compositions comprising such compounds
US6492409B1 (en) Kinase inhibitors
US7569567B2 (en) 3-Heteroaryl-3,5-dihydro-4-oxo-4H-pyridazino[4,5-B]indole-1-carboxamide derivatives, their preparation and therapeutic use
US6458792B1 (en) Compounds
EP1874777B1 (en) 1h-pyrimido[4,5-b]indole derivatives, their preparation and therapeutic use
EP1095039A2 (en) New pharmaceutically active compounds

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 09297542

Country of ref document: US

AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
NENP Non-entry into the national phase

Ref country code: KR

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase