PT1497019E - Compostos de pirrolotriazina anilina úteis como inibidores de quinase - Google Patents

Info

Publication number

PT1497019E

PT1497019E PT37241577T PT03724157T PT1497019E PT 1497019 E PT1497019 E PT 1497019E PT 37241577 T PT37241577 T PT 37241577T PT 03724157 T PT03724157 T PT 03724157T PT 1497019 E PT1497019 E PT 1497019E

Authority

PT

Portugal

Prior art keywords

alkyl

substituted

phenyl

optionally substituted

4alkyl

Prior art date

2002-04-23

Links

• Espacenet
• Global Dossier
• Discuss

• UBWMDGGQTGIGMI-UHFFFAOYSA-N NC1=CC=CC=C1.N1N=NC=C2N=CC=C21 Chemical class NC1=CC=CC=C1.N1N=NC=C2N=CC=C21 UBWMDGGQTGIGMI-UHFFFAOYSA-N 0.000 title description 3
• 229940043355 kinase inhibitor Drugs 0.000 title description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 222
• -1 diastereomers Chemical class 0.000 claims description 83
• 125000000217 alkyl group Chemical group 0.000 claims description 67
• 229910052739 hydrogen Inorganic materials 0.000 claims description 50
• 125000001072 heteroaryl group Chemical group 0.000 claims description 48
• 125000000623 heterocyclic group Chemical group 0.000 claims description 48
• 239000001257 hydrogen Substances 0.000 claims description 48
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
• 125000003118 aryl group Chemical group 0.000 claims description 37
• 150000002367 halogens Chemical class 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 35
• 229910052736 halogen Inorganic materials 0.000 claims description 34
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• 125000003545 alkoxy group Chemical group 0.000 claims description 22
• 239000012453 solvate Substances 0.000 claims description 22
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
• 150000002431 hydrogen Chemical class 0.000 claims description 21
• 125000004432 carbon atom Chemical group C* 0.000 claims description 19
• 125000000468 ketone group Chemical group 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 229930194542 Keto Natural products 0.000 claims description 18
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 16
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 15
• 229910052757 nitrogen Inorganic materials 0.000 claims description 15
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 229910052799 carbon Inorganic materials 0.000 claims description 13
• 125000004414 alkyl thio group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000003282 alkyl amino group Chemical group 0.000 claims description 9
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 8
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
• 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• 150000001721 carbon Chemical group 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
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• 125000002837 carbocyclic group Chemical group 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 125000004423 acyloxy group Chemical group 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
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• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• 125000000304 alkynyl group Chemical group 0.000 claims description 3
• 125000001769 aryl amino group Chemical group 0.000 claims description 3
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 3
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
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• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
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• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
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• 206010048873 Traumatic arthritis Diseases 0.000 claims description 2
• 125000005055 alkyl alkoxy group Chemical group 0.000 claims description 2
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• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 230000002685 pulmonary effect Effects 0.000 claims description 2
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• 229940124530 sulfonamide Drugs 0.000 claims description 2
• 150000003456 sulfonamides Chemical class 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 22
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 3
• PTUCPHGSAFOJAU-MGONOCMRSA-N (4s)-5-amino-4-[[(2s)-2-[[(2s)-2-[[(4-bromophenyl)-hydroxyphosphoryl]methyl]-3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoic acid Chemical group C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N)CP(O)(=O)C=1C=CC(Br)=CC=1)C(ON=1)=CC=1C(C=C1)=CC=C1C1=CC=CC(Cl)=C1 PTUCPHGSAFOJAU-MGONOCMRSA-N 0.000 claims 2
• 101150020251 NR13 gene Proteins 0.000 claims 2
• 125000002252 acyl group Chemical group 0.000 claims 2
• 125000003396 thiol group Chemical class [H]S* 0.000 claims 2
• RBIIKVXVYVANCQ-CUWPLCDZSA-N (2s,4s,5s)-5-amino-n-(3-amino-2,2-dimethyl-3-oxopropyl)-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-propan-2-ylhexanamide Chemical compound C1C(C)(C)N(C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)CC(=O)N1C1=CC=CC=C1Cl RBIIKVXVYVANCQ-CUWPLCDZSA-N 0.000 claims 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
• XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
• MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims 1
• ZHDHSBKTLRLUCQ-UHFFFAOYSA-N 6-[4-(6-bromo-1,2-benzothiazol-3-yl)phenoxy]-n-methyl-n-prop-2-enylhexan-1-amine Chemical group C1=CC(OCCCCCCN(C)CC=C)=CC=C1C1=NSC2=CC(Br)=CC=C12 ZHDHSBKTLRLUCQ-UHFFFAOYSA-N 0.000 claims 1
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• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 1
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• 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
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