UA78562C2 - Pyrrolo-triazine aniline compounds useful as kinase inhibitors - Google Patents

Info

Publication number

UA78562C2

UA78562C2 UA20041109628A UA20041109628A UA78562C2 UA 78562 C2 UA78562 C2 UA 78562C2 UA 20041109628 A UA20041109628 A UA 20041109628A UA 20041109628 A UA20041109628 A UA 20041109628A UA 78562 C2 UA78562 C2 UA 78562C2

Authority

UA

Ukraine

Prior art keywords

alkyl

optionally substituted

substituted

phenyl

heteroaryl

Prior art date

2002-04-23

Links

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• Global Dossier
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• 229940043355 kinase inhibitor Drugs 0.000 title abstract description 6
• 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 6
• 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 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 390
• 150000003839 salts Chemical class 0.000 claims abstract description 42
• 239000012453 solvate Substances 0.000 claims abstract description 31
• 239000000651 prodrug Substances 0.000 claims abstract description 11
• 229940002612 prodrug Drugs 0.000 claims abstract description 11
• 125000000217 alkyl group Chemical group 0.000 claims description 153
• -1 diastereomers Chemical class 0.000 claims description 143
• 125000001072 heteroaryl group Chemical group 0.000 claims description 103
• 125000000623 heterocyclic group Chemical group 0.000 claims description 95
• 229910052739 hydrogen Inorganic materials 0.000 claims description 95
• 239000001257 hydrogen Substances 0.000 claims description 94
• 229910052736 halogen Inorganic materials 0.000 claims description 83
• 150000002367 halogens Chemical class 0.000 claims description 82
• 238000000034 method Methods 0.000 claims description 74
• 125000003118 aryl group Chemical group 0.000 claims description 71
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 64
• 150000002431 hydrogen Chemical class 0.000 claims description 61
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 53
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 49
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 47
• 125000000468 ketone group Chemical group 0.000 claims description 38
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 37
• 125000003545 alkoxy group Chemical group 0.000 claims description 36
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
• 125000001188 haloalkyl group Chemical group 0.000 claims description 31
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 30
• 229910052799 carbon Inorganic materials 0.000 claims description 26
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 17
• 125000003342 alkenyl group Chemical group 0.000 claims description 15
• 125000004414 alkyl thio group Chemical group 0.000 claims description 13
• 229910052700 potassium Inorganic materials 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• 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 10
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 9
• 125000003107 substituted aryl group Chemical group 0.000 claims description 9
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
• 125000004104 aryloxy group Chemical group 0.000 claims description 8
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• 125000002837 carbocyclic group Chemical group 0.000 claims description 7
• 150000001721 carbon Chemical group 0.000 claims description 7
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 229910052770 Uranium Inorganic materials 0.000 claims description 6
• 125000002252 acyl group Chemical group 0.000 claims description 6
• 125000004423 acyloxy group Chemical group 0.000 claims description 6
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 5
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 5
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 5
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
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• 208000001132 Osteoporosis Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
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• 206010018634 Gouty Arthritis Diseases 0.000 claims description 2
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
• 229930194542 Keto Natural products 0.000 claims description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
• 206010048873 Traumatic arthritis Diseases 0.000 claims description 2
• 206010003246 arthritis Diseases 0.000 claims description 2
• 208000006673 asthma Diseases 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims description 2
• 208000024908 graft versus host disease Diseases 0.000 claims description 2
• 201000008482 osteoarthritis Diseases 0.000 claims description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 31
• 241001091551 Clio Species 0.000 claims 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
• 125000003396 thiol group Chemical class [H]S* 0.000 claims 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
• 241000538132 Moya Species 0.000 claims 1
• 150000007945 N-acyl ureas Chemical class 0.000 claims 1
• ZFZFYOLSWJXPJK-UHFFFAOYSA-N benzyl n-benzylcarbamodithioate Chemical compound C=1C=CC=CC=1CSC(=S)NCC1=CC=CC=C1 ZFZFYOLSWJXPJK-UHFFFAOYSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 90
• 239000000243 solution Substances 0.000 description 89
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
• 239000007787 solid Substances 0.000 description 63
• 230000008569 process Effects 0.000 description 57
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
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• 239000007864 aqueous solution Substances 0.000 description 42
• 239000000047 product Substances 0.000 description 41
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
• 229920006395 saturated elastomer Polymers 0.000 description 30
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
• 239000000543 intermediate Substances 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• 235000019439 ethyl acetate Nutrition 0.000 description 24
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• 238000006243 chemical reaction Methods 0.000 description 21
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• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
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• 239000008096 xylene Substances 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1