OA12292A - PyrroloÄ2,3-dÜpyrimidine compounds as immunosuppressive agents. - Google Patents
PyrroloÄ2,3-dÜpyrimidine compounds as immunosuppressive agents. Download PDFInfo
- Publication number
- OA12292A OA12292A OA1200200385A OA1200200385A OA12292A OA 12292 A OA12292 A OA 12292A OA 1200200385 A OA1200200385 A OA 1200200385A OA 1200200385 A OA1200200385 A OA 1200200385A OA 12292 A OA12292 A OA 12292A
- Authority
- OA
- OAPI
- Prior art keywords
- alkyl
- methyl
- crc6
- amino
- lrms
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 128
- 229940125721 immunosuppressive agent Drugs 0.000 title description 2
- 239000003018 immunosuppressive agent Substances 0.000 title description 2
- 108010019421 Janus Kinase 3 Proteins 0.000 claims abstract description 28
- 102000006500 Janus Kinase 3 Human genes 0.000 claims abstract description 28
- 102000001253 Protein Kinase Human genes 0.000 claims abstract description 8
- 108060006633 protein kinase Proteins 0.000 claims abstract description 8
- 239000003112 inhibitor Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 121
- -1 (CrCeJalkyl Chemical group 0.000 claims description 84
- 239000002253 acid Substances 0.000 claims description 44
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 30
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 25
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000004442 acylamino group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 12
- 229910052805 deuterium Inorganic materials 0.000 claims description 12
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 8
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 8
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- 201000004624 Dermatitis Diseases 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 230000001363 autoimmune Effects 0.000 claims description 7
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- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
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- 206010025135 lupus erythematosus Diseases 0.000 claims description 6
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- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
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- RHFWLPWDOYJEAL-UHFFFAOYSA-N 1,2-oxazol-3-amine Chemical compound NC=1C=CON=1 RHFWLPWDOYJEAL-UHFFFAOYSA-N 0.000 claims description 3
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 3
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
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- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 2
- JAUIMPSXWZMZOR-UHFFFAOYSA-N 2-[4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-1,3-thiazol-5-amine Chemical compound C1C(N(C)C=2C=3C=CNC=3N=CN=2)C(C)CCN1C1=NC=C(N)S1 JAUIMPSXWZMZOR-UHFFFAOYSA-N 0.000 claims description 2
- BNOWDJRGXLVJHD-UHFFFAOYSA-N 3-methyl-1,2-oxazol-4-amine Chemical compound CC1=NOC=C1N BNOWDJRGXLVJHD-UHFFFAOYSA-N 0.000 claims description 2
- OUQMXTJYCAJLGO-UHFFFAOYSA-N 4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(N)=N1 OUQMXTJYCAJLGO-UHFFFAOYSA-N 0.000 claims description 2
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 2
- YDALXWLQBQYZST-UHFFFAOYSA-N n-benzyl-n,4-dimethyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidine-1-carboxamide Chemical compound C1C(N(C)C=2C=3C=CNC=3N=CN=2)C(C)CCN1C(=O)N(C)CC1=CC=CC=C1 YDALXWLQBQYZST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 2
- 125000005157 alkyl carboxy group Chemical group 0.000 claims 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 2
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 125000006530 (C4-C6) alkyl group Chemical group 0.000 claims 1
- CQMHIXRPQGPCNT-UHFFFAOYSA-N 3-methyl-1,2-thiazol-5-amine Chemical compound CC=1C=C(N)SN=1 CQMHIXRPQGPCNT-UHFFFAOYSA-N 0.000 claims 1
- BAMSJXFWGUSAPN-UHFFFAOYSA-N 4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-n-(4-nitrophenyl)piperidine-1-carboxamide Chemical compound C1C(N(C)C=2C=3C=CNC=3N=CN=2)C(C)CCN1C(=O)NC1=CC=C([N+]([O-])=O)C=C1 BAMSJXFWGUSAPN-UHFFFAOYSA-N 0.000 claims 1
- KSZRXZRZFBENAS-UHFFFAOYSA-N 4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-n-[4-(methylsulfamoyl)phenyl]piperidine-1-carboxamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1NC(=O)N1CC(N(C)C=2C=3C=CNC=3N=CN=2)C(C)CC1 KSZRXZRZFBENAS-UHFFFAOYSA-N 0.000 claims 1
- JHQOCEWOJAFCTJ-UHFFFAOYSA-N 4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidine-1-carboxylic acid Chemical compound CC1CCN(C(O)=O)CC1N(C)C1=NC=NC2=C1C=CN2 JHQOCEWOJAFCTJ-UHFFFAOYSA-N 0.000 claims 1
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- IKJVHXOXTUJMHW-UHFFFAOYSA-N cyclopentyl-[4-methyl-3-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]methanone Chemical compound C1C(N(C)C=2C=3C=CNC=3N=CN=2)C(C)CCN1C(=O)C1CCCC1 IKJVHXOXTUJMHW-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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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- A61P5/00—Drugs for disorders of the endocrine system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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| Application Number | Priority Date | Filing Date | Title |
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| US21428700P | 2000-06-26 | 2000-06-26 |
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| OA1200200385A OA12292A (en) | 2000-06-26 | 2001-06-05 | PyrroloÄ2,3-dÜpyrimidine compounds as immunosuppressive agents. |
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