CA2478232C - Heterocyclic amide derivatives as cytokine inhibitors - Google Patents
Heterocyclic amide derivatives as cytokine inhibitors Download PDFInfo
- Publication number
- CA2478232C CA2478232C CA2478232A CA2478232A CA2478232C CA 2478232 C CA2478232 C CA 2478232C CA 2478232 A CA2478232 A CA 2478232A CA 2478232 A CA2478232 A CA 2478232A CA 2478232 C CA2478232 C CA 2478232C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- chosen
- pharmaceutically acceptable
- isomer
- salt
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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- -1 Heterocyclic amide Chemical class 0.000 title claims abstract description 71
- 102000004127 Cytokines Human genes 0.000 title claims abstract description 49
- 108090000695 Cytokines Proteins 0.000 title claims abstract description 49
- 239000003112 inhibitor Substances 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 131
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 48
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- 239000002253 acid Substances 0.000 claims description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 30
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000002757 morpholinyl group Chemical group 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 125000002541 furyl group Chemical group 0.000 claims description 19
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000004442 acylamino group Chemical group 0.000 claims description 16
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 13
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 12
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000004069 aziridinyl group Chemical group 0.000 claims description 11
- 150000002825 nitriles Chemical class 0.000 claims description 11
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 230000008878 coupling Effects 0.000 claims description 10
- 238000010168 coupling process Methods 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000004276 dioxalanyl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
- 125000006561 (C1-C5) alkylsulphonylamino group Chemical group 0.000 claims description 5
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 125000003435 aroyl group Chemical group 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 3
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 3
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 3
- ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 claims description 3
- BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 3
- NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 claims description 3
- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 claims description 3
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- IGRXMNYYQGKFCK-UHFFFAOYSA-N trideca-2,4,6-triene Chemical compound CCCCCCC=CC=CC=CC IGRXMNYYQGKFCK-UHFFFAOYSA-N 0.000 claims description 3
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- LJDZFAPLPVPTBD-UHFFFAOYSA-N nitroformic acid Chemical compound OC(=O)[N+]([O-])=O LJDZFAPLPVPTBD-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 abstract description 16
- 206010061218 Inflammation Diseases 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 10
- 208000037976 chronic inflammation Diseases 0.000 abstract description 4
- 230000001575 pathological effect Effects 0.000 abstract description 4
- 208000037893 chronic inflammatory disorder Diseases 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 106
- 235000019439 ethyl acetate Nutrition 0.000 description 53
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 46
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- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 34
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- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- 102000000589 Interleukin-1 Human genes 0.000 description 25
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic 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
- C07D401/02—Heterocyclic 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 two hetero rings
- C07D401/12—Heterocyclic 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 two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic 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
- C07D403/12—Heterocyclic 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 linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
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| PCT/US2003/011094 WO2003087085A1 (en) | 2002-04-11 | 2003-04-10 | Heterocyclic amide derivatives as cytokine inhibitors |
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| CA2478232A1 CA2478232A1 (en) | 2003-10-23 |
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| US7078419B2 (en) * | 2003-03-10 | 2006-07-18 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
| EP1867646A1 (en) * | 2004-05-03 | 2007-12-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
| US7285545B2 (en) | 2004-05-03 | 2007-10-23 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
| WO2006026235A1 (en) * | 2004-08-25 | 2006-03-09 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
| WO2006062982A2 (en) * | 2004-12-07 | 2006-06-15 | Locus Pharmaceuticals, Inc. | Urea inhibitors of map kinases |
| US7612200B2 (en) * | 2004-12-07 | 2009-11-03 | Locus Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| EP1838690A2 (en) * | 2004-12-21 | 2007-10-03 | Devgen N.V. | Compounds with kv4 ion channel activity |
| US8957070B2 (en) | 2005-04-20 | 2015-02-17 | Takeda Pharmaceutical Company Limited | Glucokinase activator compounds, methods of activating glucokinase and methods of treating diabetes and obesity |
| CA2635888A1 (en) * | 2006-01-04 | 2007-07-19 | Locus Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| JP5216912B2 (ja) | 2008-04-29 | 2013-06-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１受容体拮抗薬としてのインダゾール化合物 |
| JP5411927B2 (ja) * | 2008-05-06 | 2014-02-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１アンタゴニストとしてのピラゾール化合物 |
| EP2161266A1 (en) * | 2008-08-22 | 2010-03-10 | EVOTEC Neurosciences GmbH | Benzofuran derivatives as orexin receptor antagonists |
| PE20110854A1 (es) | 2008-09-26 | 2011-12-23 | Boehringer Ingelheim Int | DERIVADOS DE 1-FENIL-1H-PIRAZOLO[3,4-c]PIRIDINA-4-CARBONILAMINA COMO ANTAGONISTAS DE LOS RECEPTORES CCR1 |
| AP2012006204A0 (en) | 2009-10-21 | 2012-04-30 | Boehringer Ingelheim Int | Indazole and pyrazolopyridine compounds as CCR1 receptor antagonists. |
| JP5542214B2 (ja) | 2009-10-27 | 2014-07-09 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１受容体アンタゴニストとしての複素環化合物 |
| US8871786B2 (en) | 2010-04-30 | 2014-10-28 | Boehringer Ingelheim International Gmbh | Azaindazole amide compounds as CCR1 receptor antagonists |
| US8546442B2 (en) | 2010-12-23 | 2013-10-01 | Boehringer Ingelheim International Gmbh | Pyrazolopiperidine compounds as CCR1 receptor antagonists |
| CN121695288A (zh) | 2020-02-19 | 2026-03-20 | Epizyme股份有限公司 | Setd2抑制剂和相关方法和用途，包括组合疗法 |
| CN117510460B (zh) * | 2023-10-30 | 2026-02-06 | 贵州大学 | 一种含磺酰胺单元的苯并[b]噻吩衍生物、其制备方法及应用 |
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| DE4317076A1 (de) * | 1993-05-21 | 1994-11-24 | Bayer Ag | Benzthiophencarbonsäureamid-S-oxide |
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| US5994398A (en) * | 1996-12-11 | 1999-11-30 | Elan Pharmaceuticals, Inc. | Arylsulfonamides as phospholipase A2 inhibitors |
| US6579872B1 (en) * | 1998-05-15 | 2003-06-17 | Astrazeneca Ab | Bezamide derivatives for the treatment of diseases mediated by cytokines |
| ATE254105T1 (de) | 1998-09-25 | 2003-11-15 | Astrazeneca Ab | Benzamid-derivate und ihre verwendung als cytokine inhibitoren |
| TR200102817T2 (tr) | 1999-03-12 | 2002-05-21 | Boehringer Ingelheim Pharmaceuticals, Inc. | Antiinflamatuar ajanlar olarak faydalı bileşikler |
| TWI288745B (en) * | 2000-04-05 | 2007-10-21 | Daiichi Seiyaku Co | Ethylenediamine derivatives |
| WO2002012189A1 (en) * | 2000-08-09 | 2002-02-14 | Mitsubishi Pharma Corporation | Fused bicyclic amide compounds and medicinal use thereof |
| MXPA03009000A (es) | 2001-04-13 | 2004-02-12 | Boehringer Ingelheim Pharma | Compuestos benzo-fusionados 1,4-disustituidos. |
| AR034897A1 (es) * | 2001-08-07 | 2004-03-24 | Hoffmann La Roche | Derivados n-monoacilados de o-fenilendiaminas, sus analogos heterociclicos de seis miembros y su uso como agentes farmaceuticos |
| EP1497278B1 (en) * | 2002-04-11 | 2010-05-26 | Boehringer Ingelheim Pharmaceuticals Inc. | Heterocyclic amide derivatives as cytokine inhibitors |
-
2003
- 2003-04-10 EP EP03721619A patent/EP1497278B1/en not_active Expired - Lifetime
- 2003-04-10 ES ES03721619T patent/ES2343787T3/es not_active Expired - Lifetime
- 2003-04-10 JP JP2003584041A patent/JP4578106B2/ja not_active Expired - Lifetime
- 2003-04-10 AT AT03721619T patent/ATE469142T1/de active
- 2003-04-10 AU AU2003224923A patent/AU2003224923A1/en not_active Abandoned
- 2003-04-10 CA CA2478232A patent/CA2478232C/en not_active Expired - Lifetime
- 2003-04-10 WO PCT/US2003/011094 patent/WO2003087085A1/en not_active Ceased
- 2003-04-10 DE DE60332717T patent/DE60332717D1/de not_active Expired - Lifetime
- 2003-04-10 US US10/410,688 patent/US7550461B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US20030225053A1 (en) | 2003-12-04 |
| JP2005530730A (ja) | 2005-10-13 |
| CA2478232A1 (en) | 2003-10-23 |
| EP1497278B1 (en) | 2010-05-26 |
| WO2003087085A1 (en) | 2003-10-23 |
| AU2003224923A1 (en) | 2003-10-27 |
| JP4578106B2 (ja) | 2010-11-10 |
| DE60332717D1 (de) | 2010-07-08 |
| ATE469142T1 (de) | 2010-06-15 |
| EP1497278A1 (en) | 2005-01-19 |
| ES2343787T3 (es) | 2010-08-10 |
| US7550461B2 (en) | 2009-06-23 |
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