JP5643347B2 - 新規酵素阻害化合物 - Google Patents

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Publication number

JP5643347B2

JP5643347B2 JP2012557516A JP2012557516A JP5643347B2 JP 5643347 B2 JP5643347 B2 JP 5643347B2 JP 2012557516 A JP2012557516 A JP 2012557516A JP 2012557516 A JP2012557516 A JP 2012557516A JP 5643347 B2 JP5643347 B2 JP 5643347B2

Authority

JP

Japan

Prior art keywords

alkyl

pyrrolo

mmol

pyridin

chlorophenyl

Prior art date

2010-03-15

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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• 150000001875 compounds Chemical class 0.000 title claims description 243
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• 108090000790 Enzymes Proteins 0.000 title description 17
• 230000002401 inhibitory effect Effects 0.000 title description 3
• -1 cyano, amino, hydroxyl Chemical group 0.000 claims description 141
• 238000000034 method Methods 0.000 claims description 89
• 125000000217 alkyl group Chemical group 0.000 claims description 74
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 47
• 229920006395 saturated elastomer Polymers 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
• 150000002431 hydrogen Chemical class 0.000 claims description 19
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 150000001204 N-oxides Chemical class 0.000 claims description 17
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
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• 125000003277 amino group Chemical group 0.000 claims description 11
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• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
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• 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 8
• 125000002757 morpholinyl group Chemical group 0.000 claims description 8
• 125000004193 piperazinyl group Chemical group 0.000 claims description 8
• 125000003386 piperidinyl group Chemical group 0.000 claims description 8
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• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
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• 229910052731 fluorine Inorganic materials 0.000 claims description 6
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• UXBOPANQZQDGFP-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[1-(1h-pyrazol-5-ylmethyl)piperidin-4-yl]pyrrolo[2,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1N1C2=CN=CC=C2C(C2CCN(CC3=NNC=C3)CC2)=C1 UXBOPANQZQDGFP-UHFFFAOYSA-N 0.000 claims description 3
• BCTZJRGISGITFZ-UHFFFAOYSA-N 1-[4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C1CN(C(=O)CN(C)C)CCC1C(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 BCTZJRGISGITFZ-UHFFFAOYSA-N 0.000 claims description 3
• VIUQFKJKEZNIOV-UHFFFAOYSA-N 1-[4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]-2-hydroxyethanone Chemical compound C1CN(C(=O)CO)CCC1C(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 VIUQFKJKEZNIOV-UHFFFAOYSA-N 0.000 claims description 3
• PVKFTMXILNTSOY-UHFFFAOYSA-N 1-[[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]methyl]piperidin-4-ol Chemical compound C1CC(O)CCN1CC(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 PVKFTMXILNTSOY-UHFFFAOYSA-N 0.000 claims description 3
• SNUPNVCHYSJETG-UHFFFAOYSA-N 2-[4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethanol Chemical compound C1CN(CCO)CCC1C(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 SNUPNVCHYSJETG-UHFFFAOYSA-N 0.000 claims description 3
• FGYKHVGONVOUOE-UHFFFAOYSA-N 4-[[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]methyl]morpholine Chemical compound C1=CC(Cl)=CC=C1N1C2=CN=CC=C2C(CN2CCOCC2)=C1 FGYKHVGONVOUOE-UHFFFAOYSA-N 0.000 claims description 3
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• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
• 206010016654 Fibrosis Diseases 0.000 claims description 3
• 206010019280 Heart failures Diseases 0.000 claims description 3
• 201000008937 atopic dermatitis Diseases 0.000 claims description 3
• 230000001363 autoimmune Effects 0.000 claims description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
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• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 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 3
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 3
• FUESDKXSKZBKIW-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-(piperazin-1-ylmethyl)pyrrolo[2,3-c]pyridine Chemical compound C1=CC(Cl)=CC=C1N1C2=CN=CC=C2C(CN2CCNCC2)=C1 FUESDKXSKZBKIW-UHFFFAOYSA-N 0.000 claims description 2
• ICTHLQAYBCVJAA-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[1-[(1-methylpyrazol-4-yl)methyl]piperidin-4-yl]pyrrolo[2,3-c]pyridine Chemical compound C1=NN(C)C=C1CN1CCC(C=2C3=CC=NC=C3N(C=3C=CC(Cl)=CC=3)C=2)CC1 ICTHLQAYBCVJAA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• AGOLRJPOKXWUNE-UHFFFAOYSA-N 2-[1-[[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]methyl]piperidin-4-yl]ethanol Chemical compound C1CC(CCO)CCN1CC(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 AGOLRJPOKXWUNE-UHFFFAOYSA-N 0.000 claims description 2
• ZZPKYLOQWXZCBX-UHFFFAOYSA-N 2-[[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]methylamino]ethanol Chemical compound C12=CN=CC=C2C(CNCCO)=CN1C1=CC=C(Cl)C=C1 ZZPKYLOQWXZCBX-UHFFFAOYSA-N 0.000 claims description 2
• WDTBPWKPLTZJPQ-UHFFFAOYSA-N 2-amino-1-[4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)CN)CCC1C(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 WDTBPWKPLTZJPQ-UHFFFAOYSA-N 0.000 claims description 2
• GIYVZZSXUQYABS-UHFFFAOYSA-N 3-(3,6-dihydro-2h-pyran-4-yl)-2-methyl-1-(4-methylphenyl)pyrrolo[2,3-c]pyridine Chemical compound C12=CC=NC=C2N(C=2C=CC(C)=CC=2)C(C)=C1C1=CCOCC1 GIYVZZSXUQYABS-UHFFFAOYSA-N 0.000 claims description 2
• SXONDVGUWVLMQZ-UHFFFAOYSA-N 3-amino-1-[4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]propan-1-one Chemical compound C1CN(C(=O)CCN)CCC1C(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 SXONDVGUWVLMQZ-UHFFFAOYSA-N 0.000 claims description 2
• GWESHTVIEYBLRM-UHFFFAOYSA-N 4-amino-1-[4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]butan-1-one Chemical compound C1CN(C(=O)CCCN)CCC1C(C1=CC=NC=C11)=CN1C1=CC=C(Cl)C=C1 GWESHTVIEYBLRM-UHFFFAOYSA-N 0.000 claims description 2
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