JP5323484B2 - ピラゾロ［３，４−ｂ］ピリジン化合物及びそのＰＤＥ４阻害薬としての使用 - Google Patents

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Publication number

JP5323484B2

JP5323484B2 JP2008532873A JP2008532873A JP5323484B2 JP 5323484 B2 JP5323484 B2 JP 5323484B2 JP 2008532873 A JP2008532873 A JP 2008532873A JP 2008532873 A JP2008532873 A JP 2008532873A JP 5323484 B2 JP5323484 B2 JP 5323484B2

Authority

JP

Japan

Prior art keywords

methyl

ring

formula

alkyl

independently

Prior art date

2005-09-29

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 - Fee Related

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• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 60
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title description 58
• 150000005230 pyrazolo[3,4-b]pyridines Chemical class 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 332
• 150000003839 salts Chemical class 0.000 claims abstract description 236
• -1 C1-2fluoroalkyl Chemical group 0.000 claims abstract description 230
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 193
• 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 112
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 91
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 54
• 238000011282 treatment Methods 0.000 claims abstract description 52
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 40
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 21
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 15
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 15
• 208000026935 allergic disease Diseases 0.000 claims abstract description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 8
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 4
• 125000001424 substituent group Chemical group 0.000 claims description 231
• 125000000217 alkyl group Chemical group 0.000 claims description 207
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 161
• 229910052799 carbon Inorganic materials 0.000 claims description 151
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 106
• 229910052757 nitrogen Inorganic materials 0.000 claims description 91
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 84
• 230000036961 partial effect Effects 0.000 claims description 76
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 68
• 125000001153 fluoro group Chemical group F* 0.000 claims description 67
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• NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 59
• 125000003545 alkoxy group Chemical group 0.000 claims description 50
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 48
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 46
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• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 35
• 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 34
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 25
• 229910052760 oxygen Inorganic materials 0.000 claims description 25
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
• 229910052717 sulfur Inorganic materials 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 23
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 22
• 230000002265 prevention Effects 0.000 claims description 22
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 21
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• 125000004076 pyridyl group Chemical group 0.000 claims description 20
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 18
• 229910052801 chlorine Inorganic materials 0.000 claims description 17
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
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• 125000005842 heteroatom Chemical group 0.000 claims description 15
• 125000004429 atom Chemical group 0.000 claims description 14
• 229910005965 SO 2 Inorganic materials 0.000 claims description 13
• SVSARCCKBMZNMR-UHFFFAOYSA-N [1-[2-[methyl-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethyl]amino]ethyl]pyridin-4-ylidene]methyl-oxoazanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1CCN(C)CCN1C=CC(=C[NH+]=O)C=C1 SVSARCCKBMZNMR-UHFFFAOYSA-N 0.000 claims description 13
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• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
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• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
• 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 11
• 125000006413 ring segment Chemical group 0.000 claims description 11
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• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
• 239000013543 active substance Substances 0.000 claims description 7
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
• 229910052740 iodine Inorganic materials 0.000 claims description 7
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 6
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 6
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 6
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 125000002883 imidazolyl group Chemical group 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• 125000001425 triazolyl group Chemical group 0.000 claims description 6
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
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• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
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