1,2-dihydro-4-hydroxy-2-oxo-quinoline-3-carboxanilides as AHR activators

• US 8,962,598 B2
• Filed: 10/11/2011
• Issued: 02/24/2015
• Est. Priority Date: 10/14/2010
• Status: Active Grant

• Current Assignee: Immunahr AB
• Original Assignee: Immunahr AB
• Inventors: Pettersson, Lars
• Primary Examiner(s): REESE, HEIDI L
• Application Number:
  US13/824,256
• Publication Number:
  US 20130203703A1
• Time in Patent Office: 1,232 Days
• Field of Search: None
• US Class Current: 514/82
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 215/56 : with oxygen atoms in position 4
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07F 9/60 : Quinoline or hydrogenated quinoline ring systems

Abstract

The present invention relates to compounds which are 1,2-dihydro-4-hydroxy-2-oxo-quinoline-3-carboxanilides, their thieno-pyridone analogs, and prodrugs thereof. This invention specifically relates to such derivatives containing an N-hydrogen in the carboxanilide moiety and which exhibit modulating activity towards the aromatic hydrocarbon receptor (AhR), and, specifically, also to prodrugs thereof. The present invention also relates to use of said compounds as a medicament, and for the treatment of cancer, autoimmune disorders and other disorders with an immunological component, and a pharmaceutical composition comprising one or more of said compounds and a method of treatment.

Claims

1. A compound of the general formula I or a pharmaceutically acceptable salt thereof:

2. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

A, B and C are independently selected from the group consisting of H, Me, OMe, CF₃, OCF₃, F, Cl, and Br, or A and B represents OCH₂O and C is H;

and

R5 and R6 are independently selected from the group consisting of H, Me, Et, OMe, SMe, S(O)Me, CF₃, OCF₃, F, Cl, and Br, or R5 and R6 represents OCH₂O.

3. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

A, B and C are independently selected from the group consisting of Me, OMe, CF₃, OCF₃, F, and Cl, or A and B represents OCH₂O and C is H;

and

R5 and R6 are independently selected from the group consisting of Me, Et, OMe, SMe, S(O)Me, CF₃, F, and Cl, or R5 and R6 represents OCH₂O.

4. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

RN is selected from the group consisting of H, C(O)Me, C(O)Et, C(O)Pr, C(O)CH(Me)₂, C(O)C(Me)₃, C(O)Ph, C(O)CH₂Ph, CO₂Me, CO₂Et, and,

R4 is RN, or when RN is H, then R4 is selected from the group consisting of P(O)(OH)₂, P(O)(OMe)₂, P(O)(OEt)₂, P(O)(OPh)₂, P(O)(OCH₂Ph)₂, C(O)Me, C(O)Et, C(O)Pr, C(O)CH(Me)₂, C(O)C(Me)₃, C(O)Ph, C(O)CH₂Ph, CO₂Me and CO₂Et;

with the proviso that R4 is not H.

5. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

RN is selected from the group consisting of C(O)Me, C(O)Et, C(O)Pr, C(O)CH(Me)₂, C(O)C(Me)₃, C(O)Ph, CO₂Me, and CO₂Et;

and

R4 is RN.

6. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

RN is H;

and

R4 is selected from the group consisting of P(O)(OH)₂, P(O)(OMe)₂, P(O)(OEt)₂, P(O)(OPh)₂, P(O)(OCH₂Ph)₂, C(O)Me, C(O)Et, C(O)Pr, C(O)CH(Me)₂, C(O)C(Me)₃, C(O)Ph, C(O)CH₂Ph, CO₂Me and CO₂Et.

7. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

RN is H;

and

R4 is H.

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein

X is S.

9. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein

A, B and C are independently selected from the group consisting of H, Me, OMe, CF₃, OCF₃, F, Cl, and Br, or A and B represents OCH₂O and C is H;

R5 is selected from the group consisting of H, Me, Et, CF₃, Cl, and Br;

R6 is H; and

X is S.

10. The compound or a pharmaceutically acceptable salt thereof according to claim 1, which is selected from the group consisting of

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-diethylphosphoryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methylphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methylphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-methylphenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methylphenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-methylphenyl)-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-methylphenyl)-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-fluorophenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-fluorophenyl)-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-fluorophenyl)-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-chlorophenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-chlorophenyl)-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-N-ethoxycarbonyl-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-methoxyphenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-methoxyphenyl)-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-methoxyphenyl)-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-trifluoromethylphenyl)-4-iso-butyryloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-trifluoromethylphenyl)-4-benzoyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-trifluoromethylphenyl)-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-trifluoromethoxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethoxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(3,4-difluorophenyl)-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(3,4-difluorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(3,4-difluorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(3,5-di-(trifluoromethyl)phenyl)-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methylthiophenyl)-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(3,4-methylenedioxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methylenedioxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-1,2-dihydro-4-hydroxy-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-1,2-dihydro-4-hydroxy-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-1,5-dimethyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-5-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-diethylphosphoryloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-5-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-iso-butyryloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-chlorophenyl)-4-benzoyloxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-5-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-5-ethyl-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-5-trifluoromethyl-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-5-trifluoromethyl-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-5-trifluoromethyl-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-fluorophenyl)-4-iso-butyryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-iso-butyryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-fluorophenyl)-4-benzoyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-benzoyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-trifluoromethylphenyl)-4-iso-butyryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-4-iso-butyryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-trifluoromethylphenyl)-4-benzoyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-4-benzoyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-trifluoromethylphenyl)-4-ethoxycarbonyloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-trifluoromethylphenyl)-4-diethylphosphoryloxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-5-fluoro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-5-fluoro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-diethylphosphoryloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methylphenyl)-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methylphenyl)-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methylphenyl)-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-methylphenyl)-5-chloro-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-methoxyphenyl)-4-iso-butyryloxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-5-bromo-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-5-bromo-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-5-bromo-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-1-methyl-5-methylthio-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-5-methylthio-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-5-methylthio-2-oxo-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-1,2-dihydro-4-hydroxy-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-N-phenyl-4-acetoxy-1,2-dihydro-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-1,2-dihydro-4-hydroxy-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-N-phenyl-4-acetoxy-1,2-dihydro-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-5,6-methylenedioxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1,6-dimethyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1,6-dimethyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-6-trifluoromethyl-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-6-trifluoromethyl-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-6-trifluoromethyl-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-diethylphosphoryloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-1,2-dihydro-4-hydroxy-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-fluorophenyl)-4-iso-butyryloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-fluorophenyl)-4-benzoyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-fluorophenyl)-4-ethoxycarbonyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-1,2-dihydro-4-hydroxy-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-chlorophenyl)-4-iso-butyryloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-chlorophenyl)-4-benzoyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-N-ethoxycarbonyl-4-ethoxycarbonyloxy-1,2-dihydro-6-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-6-trifluoromethoxy-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-6-trifluoromethoxy-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-2-oxo-6-trifluoromethoxy-quinoline-3-carboxamide,

N-phenyl-6-fluoro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-6-fluoro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-6-fluoro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-diethylphosphoryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-6-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-fluorophenyl)-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-n-butyryl-N-(4-fluorophenyl)-4-n-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-fluorophenyl)-4-iso-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-fluorophenyl)-4-benzoyloxy-6-chloro-1,2-dihydro1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-fluorophenyl)-6-chloro-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-6-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-n-butyryl-N-(4-chlorophenyl)-4-n-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-chlorophenyl)-4-iso-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-chlorophenyl)-4-benzoyloxy-6-chloro-1,2-dihydro1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-N-ethoxycarbonyl-6-chloro-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-6-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-n-butyryl-N-(4-methoxyphenyl)-4-n-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-(4-methoxyphenyl)-4-iso-butyryloxy-6-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-(4-methoxyphenyl)-4-benzoyloxy-6-chloro-1,2-dihydro1-methyl-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-(4-methoxyphenyl)-6-chloro-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-6-bromo-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-6-bromo-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-6-bromo-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-iso-butyryloxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-benzoyloxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-diethylphosphoryloxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-1,2-dihydro-4-hydroxy-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-(4-fluorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-1,2-dihydro-4-hydroxy-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-1,2-dihydro-4-hydroxy-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-1,2-dihydro-1-methyl-6-methylthio-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-1,2-dihydro-4-hydroxy-1-methyl-6-methylsulfinyl-2-oxo-quinoline-3-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-6-methylsulfinyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-4-acetoxy-1,2-dihydro-1-methyl-6-methylsulfinyl-2-oxo-quinoline-3-carboxamide,

N-phenyl-6,7-dihydro-4-hydroxy-7-methyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-6,7-dihydro-7-methyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-4-acetoxy-6,7-dihydro-7-methyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-6,7-dihydro-4-hydroxy-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-19]pyridine-5-carboxamide,

N-iso-butyryl-N-phenyl-4-iso-butyryloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-4-iso-butyryloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-benzoyl-N-phenyl-4-benzoyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-4-benzoyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-ethoxycarbonyl-N-phenyl-4-ethoxycarbonyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-4-diethylphosphoryloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-(4-fluorophenyl)-6,7-dihydro-4-hydroxy-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-(4-fluorophenyl)-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-(4-fluorophenyl)-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-iso-butyryl-N-(4-fluorophenyl)-4-iso-butyryloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-benzoyl-N-(4-fluorophenyl)-4-benzoyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-ethoxycarbonyl-N-(4-fluorophenyl)-4-ethoxycarbonyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-(4-chlorophenyl)-6,7-dihydro-4-hydroxy-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-(4-chlorophenyl)-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-(4-chlorophenyl)-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-(4-methoxyphenyl)-6,7-dihydro-4-hydroxy-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-(4-methoxyphenyl)-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-(4-methoxyphenyl)-4-acetoxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-iso-butyryl-N-(4-methoxyphenyl)-4-iso-butyryloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-benzoyl-N-(4-methoxyphenyl)-4-benzoyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-ethoxycarbonyl-N-(4-methoxyphenyl)-4-ethoxycarbonyloxy-6,7-dihydro-3,7-dimethyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-3-ethyl-6,7-dihydro-4-hydroxy-7-methyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-3-ethyl-6,7-dihydro-7-methyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-4-acetoxy-3-ethyl-6,7-dihydro-7-methyl-6-oxo-thieno[2,3-b]pyridine-5-carboxamide,

N-phenyl-6,7-dihydro-4-hydroxy-7-methyl-6-oxo-3-trifluoromethyl-thieno[2,3-b]pyridine-5-carboxamide,

N-acetyl-N-phenyl-4-acetoxy-6,7-dihydro-7-methyl-6-oxo-3-trifluoromethyl-thieno[2,3-b]pyridine-5-carboxamide, and

N-phenyl-4-acetoxy-6,7-dihydro-7-methyl-6-oxo-3-trifluoromethyl-thieno[2,3-b]pyridine-5-carboxamide.

11. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1, admixed with one or more pharmaceutically acceptable excipients or carriers.

12. The pharmaceutical composition according to claim 11, wherein the excipients are selected from the group consisting of filling agents, lubricants, flavours, colourings, sweetenings, buffers, acidifying agents, diluents, and preservatives.

13. The pharmaceutical composition according to claim 11, which is suitable for administration by one or more of orally, by oral inhalation, intramuscularly, intravenously, intraperitoneally, or subcutaneously, via implants, rectally, intranasally, or transdermally.

14. A method of treatment comprising

administration of a pharmaceutically effective amount of the compound or a pharmaceutically acceptable salt thereof according to claim 1 or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof according to claim 1, admixed with one or more pharmaceutically acceptable excipients or carriers to a subject suffering from cancer, autoimmune disorder, or other disorder with an immunological component, wherein the disorder with an immunological component is selected from the group consisting of asthma, allergy, infection, bone loss, atherosclerosis, diabetes type 2, graft-versus-host, and transplant rejection.

15. The method of treatment according to claim 14, wherein the method is for the treatment of cancer and the subject is suffering from a cancer selected from the group consisting of prostate cancer, intestinal cancer, and leukemia.

16. The method of treatment according to claim 14, wherein the method is for the treatment of an autoimmune disorder and the subject is suffering from an autoimmune disorder selected from the group consisting of rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, diabetes type 1, and psoriasis.

17. The method of treatment according to claim 14, wherein the method is for the treatment of a disorder with an immunological component and the subject is suffering from a disorder with an immunological component selected from the group consisting of asthma, allergy, infection, bone loss, atherosclerosis, diabetes type 2, graft-versus-host, and transplant rejection.

18. The pharmaceutical composition according to claim 13, which is suitable to be administered orally.