JP2006500348A - サイクリン依存キナーゼ(cdk)インヒビターとしての1h−インダゾール−3−カルボキサミド化合物 - Google Patents
サイクリン依存キナーゼ(cdk)インヒビターとしての1h−インダゾール−3−カルボキサミド化合物 Download PDFInfo
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- JP2006500348A JP2006500348A JP2004527053A JP2004527053A JP2006500348A JP 2006500348 A JP2006500348 A JP 2006500348A JP 2004527053 A JP2004527053 A JP 2004527053A JP 2004527053 A JP2004527053 A JP 2004527053A JP 2006500348 A JP2006500348 A JP 2006500348A
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- indazole
- carboxylic acid
- hydrogen
- compound
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- 108090000266 Cyclin-dependent kinases Proteins 0.000 title claims abstract description 64
- 102000003903 Cyclin-dependent kinases Human genes 0.000 title claims abstract description 63
- 239000003112 inhibitor Substances 0.000 title description 9
- 150000008581 1H-indazole-3-carboxamides Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 435
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 172
- 239000001257 hydrogen Substances 0.000 claims abstract description 172
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 159
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 125
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 105
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 97
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 80
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 43
- 238000011282 treatment Methods 0.000 claims abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 34
- 201000010099 disease Diseases 0.000 claims abstract description 30
- 125000005647 linker group Chemical group 0.000 claims abstract description 23
- 230000002265 prevention Effects 0.000 claims abstract description 16
- 125000002015 acyclic group Chemical group 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 14
- FPDZIMRJMRTOKM-UHFFFAOYSA-N 1-phenylindazole-3-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)N)=NN1C1=CC=CC=C1 FPDZIMRJMRTOKM-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 7
- -1 cyano, nitro, carboxy, amino Chemical group 0.000 claims description 158
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 139
- 125000001424 substituent group Chemical group 0.000 claims description 95
- 150000002367 halogens Chemical class 0.000 claims description 79
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 72
- 150000002431 hydrogen Chemical class 0.000 claims description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 61
- 108091007914 CDKs Proteins 0.000 claims description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000004043 oxo group Chemical group O=* 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- 125000004429 atom Chemical group 0.000 claims description 25
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 25
- 125000004122 cyclic group Chemical group 0.000 claims description 25
- 230000000694 effects Effects 0.000 claims description 25
- 239000000460 chlorine Substances 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 17
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 17
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000002619 bicyclic group Chemical group 0.000 claims description 10
- 230000010261 cell growth Effects 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 108091000080 Phosphotransferase Proteins 0.000 claims description 9
- 230000002159 abnormal effect Effects 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 102000020233 phosphotransferase Human genes 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- HESAABVMXUIIBT-UHFFFAOYSA-N 5-iodo-n-[4-(methylsulfamoylmethyl)phenyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C(I)C=C12 HESAABVMXUIIBT-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 150000003857 carboxamides Chemical group 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- HGNCHXJDBBMVAP-UHFFFAOYSA-N n-[4-(methylsulfamoylmethyl)phenyl]-5-nitro-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C([N+]([O-])=O)C=C12 HGNCHXJDBBMVAP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- UBVGOYYYXPTKQU-UHFFFAOYSA-N 5-amino-n-phenyl-1h-indazole-3-carboxamide Chemical compound C12=CC(N)=CC=C2NN=C1C(=O)NC1=CC=CC=C1 UBVGOYYYXPTKQU-UHFFFAOYSA-N 0.000 claims description 5
- 229940121375 antifungal agent Drugs 0.000 claims description 5
- 230000032823 cell division Effects 0.000 claims description 5
- VDQVUXZQLQVTFP-UHFFFAOYSA-N n-[(4-methylphenyl)methyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(C)=CC=C1CNC(=O)C1=NNC2=CC=CC=C12 VDQVUXZQLQVTFP-UHFFFAOYSA-N 0.000 claims description 5
- DQAFCEKOSHMUDW-UHFFFAOYSA-N n-[4-(methylsulfamoylmethyl)phenyl]-5-thiophen-2-yl-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C(C=3SC=CC=3)C=C12 DQAFCEKOSHMUDW-UHFFFAOYSA-N 0.000 claims description 5
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 4
- RPLSBADGISFNSI-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxane Chemical group CC1(C)OCCCO1 RPLSBADGISFNSI-UHFFFAOYSA-N 0.000 claims description 4
- RXGCJGDBXJXINL-UHFFFAOYSA-N 4-bromo-n-(4-fluorophenyl)-1h-indazole-3-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=NNC2=CC=CC(Br)=C12 RXGCJGDBXJXINL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- JNYYMIIPAARGFV-UHFFFAOYSA-N 5-amino-4-bromo-n-(4-fluorophenyl)-1h-indazole-3-carboxamide Chemical compound C12=C(Br)C(N)=CC=C2NN=C1C(=O)NC1=CC=C(F)C=C1 JNYYMIIPAARGFV-UHFFFAOYSA-N 0.000 claims description 4
- RMPAGVOOOZIKIE-UHFFFAOYSA-N 5-amino-n-(4-fluorophenyl)-1h-indazole-3-carboxamide Chemical compound C12=CC(N)=CC=C2NN=C1C(=O)NC1=CC=C(F)C=C1 RMPAGVOOOZIKIE-UHFFFAOYSA-N 0.000 claims description 4
- MPLCAPIYKIZONA-UHFFFAOYSA-N 5-amino-n-(4-sulfamoylphenyl)-1h-indazole-3-carboxamide Chemical compound C12=CC(N)=CC=C2NN=C1C(=O)NC1=CC=C(S(N)(=O)=O)C=C1 MPLCAPIYKIZONA-UHFFFAOYSA-N 0.000 claims description 4
- XOHBJURTSXDOOR-UHFFFAOYSA-N 5-morpholin-4-yl-n-phenyl-1h-indazole-3-carboxamide Chemical compound N=1NC2=CC=C(N3CCOCC3)C=C2C=1C(=O)NC1=CC=CC=C1 XOHBJURTSXDOOR-UHFFFAOYSA-N 0.000 claims description 4
- JUDMZRUIYAAHQP-UHFFFAOYSA-N 6-bromo-n-(4-fluorophenyl)-1h-indazole-3-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=NNC2=CC(Br)=CC=C12 JUDMZRUIYAAHQP-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 150000002460 imidazoles Chemical group 0.000 claims description 4
- 125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 4
- YQSIWFYOCLSGND-UHFFFAOYSA-N n-(1-benzylpyrrolidin-3-yl)-5-chloro-1h-indazole-3-carboxamide Chemical compound C12=CC(Cl)=CC=C2NN=C1C(=O)NC(C1)CCN1CC1=CC=CC=C1 YQSIWFYOCLSGND-UHFFFAOYSA-N 0.000 claims description 4
- YHDDTWWWTGIOMQ-UHFFFAOYSA-N n-(4-fluorophenyl)-1h-indazole-3-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=NNC2=CC=CC=C12 YHDDTWWWTGIOMQ-UHFFFAOYSA-N 0.000 claims description 4
- TVMTUXFGZGSXOA-UHFFFAOYSA-N n-(4-fluorophenyl)-5-methyl-1h-indazole-3-carboxamide Chemical compound C12=CC(C)=CC=C2NN=C1C(=O)NC1=CC=C(F)C=C1 TVMTUXFGZGSXOA-UHFFFAOYSA-N 0.000 claims description 4
- IJYHVPGIDGXMEA-UHFFFAOYSA-N n-(4-fluorophenyl)-5-nitro-1h-indazole-3-carboxamide Chemical compound C12=CC([N+](=O)[O-])=CC=C2NN=C1C(=O)NC1=CC=C(F)C=C1 IJYHVPGIDGXMEA-UHFFFAOYSA-N 0.000 claims description 4
- ZKUWYWIZUUHKHS-UHFFFAOYSA-N n-[1-(2,2,2-trifluoroacetyl)piperidin-4-yl]-1h-indazole-3-carboxamide Chemical compound C1CN(C(=O)C(F)(F)F)CCC1NC(=O)C1=NNC2=CC=CC=C12 ZKUWYWIZUUHKHS-UHFFFAOYSA-N 0.000 claims description 4
- KBEORDFRUUGOKD-UHFFFAOYSA-N n-[4-(acetamidomethyl)phenyl]-5-iodo-1h-indazole-3-carboxamide Chemical compound C1=CC(CNC(=O)C)=CC=C1NC(=O)C1=NNC2=CC=C(I)C=C12 KBEORDFRUUGOKD-UHFFFAOYSA-N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical group C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 4
- IZYQNASJMRZALI-UHFFFAOYSA-N 5-(1,1-dioxo-1,2-thiazolidin-2-yl)-n-phenyl-1h-indazole-3-carboxamide Chemical compound N=1NC2=CC=C(N3S(CCC3)(=O)=O)C=C2C=1C(=O)NC1=CC=CC=C1 IZYQNASJMRZALI-UHFFFAOYSA-N 0.000 claims description 3
- YXTCIEINXMOZTA-UHFFFAOYSA-N 5-(1-benzofuran-2-yl)-n-[4-(methylsulfamoylmethyl)phenyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C(C=3OC4=CC=CC=C4C=3)C=C12 YXTCIEINXMOZTA-UHFFFAOYSA-N 0.000 claims description 3
- NFCOAOZBPUSALA-UHFFFAOYSA-N 5-(3,5-dimethyl-1,2-oxazol-4-yl)-n-[4-(methylsulfamoylmethyl)phenyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C(C3=C(ON=C3C)C)C=C12 NFCOAOZBPUSALA-UHFFFAOYSA-N 0.000 claims description 3
- CNNSJGIRPUSXRR-UHFFFAOYSA-N 5-(furan-2-yl)-n-[4-(methylsulfamoylmethyl)phenyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C(C=3OC=CC=3)C=C12 CNNSJGIRPUSXRR-UHFFFAOYSA-N 0.000 claims description 3
- DHZJCZYUMMTBDV-UHFFFAOYSA-N 5-amino-n-[4-(methylsulfamoylmethyl)phenyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1NC(=O)C1=NNC2=CC=C(N)C=C12 DHZJCZYUMMTBDV-UHFFFAOYSA-N 0.000 claims description 3
- SDWUOUQMDLEZHL-UHFFFAOYSA-N 5-chloro-n-[5-(oxolan-2-yl)-1,3,4-thiadiazol-2-yl]-1h-indazole-3-carboxamide Chemical compound C12=CC(Cl)=CC=C2NN=C1C(=O)NC(S1)=NN=C1C1CCCO1 SDWUOUQMDLEZHL-UHFFFAOYSA-N 0.000 claims description 3
- DQXPXOGAPAHRSV-UHFFFAOYSA-N 5-iodo-n-(3-methylsulfonylphenyl)-1h-indazole-3-carboxamide Chemical compound CS(=O)(=O)C1=CC=CC(NC(=O)C=2C3=CC(I)=CC=C3NN=2)=C1 DQXPXOGAPAHRSV-UHFFFAOYSA-N 0.000 claims description 3
- DKFPLBWBXFDNAP-UHFFFAOYSA-N 5-iodo-n-(4-sulfamoylphenyl)-1h-indazole-3-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC(=O)C1=NNC2=CC=C(I)C=C12 DKFPLBWBXFDNAP-UHFFFAOYSA-N 0.000 claims description 3
- BFADRLFGMKINDD-UHFFFAOYSA-N 5-iodo-n-phenyl-1h-indazole-3-carboxamide Chemical compound C12=CC(I)=CC=C2NN=C1C(=O)NC1=CC=CC=C1 BFADRLFGMKINDD-UHFFFAOYSA-N 0.000 claims description 3
- BFFLNPVHTQDZBX-UHFFFAOYSA-N 5-iodo-n-piperidin-4-yl-1h-indazole-3-carboxamide Chemical compound C12=CC(I)=CC=C2NN=C1C(=O)NC1CCNCC1 BFFLNPVHTQDZBX-UHFFFAOYSA-N 0.000 claims description 3
- WUGGEQNWXURWBN-UHFFFAOYSA-N 5-nitro-n-(4-sulfamoylphenyl)-1h-indazole-3-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC(=O)C1=NNC2=CC=C([N+]([O-])=O)C=C12 WUGGEQNWXURWBN-UHFFFAOYSA-N 0.000 claims description 3
- OXQNJTNCHYXAEK-UHFFFAOYSA-N 7-amino-n-(4-sulfamoylphenyl)-2h-indazole-3-carboxamide Chemical compound N=1NC=2C(N)=CC=CC=2C=1C(=O)NC1=CC=C(S(N)(=O)=O)C=C1 OXQNJTNCHYXAEK-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 239000003429 antifungal agent Substances 0.000 claims description 3
- 230000033077 cellular process Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- WVBGCSKNPACHSD-UHFFFAOYSA-N methyl 3-[(5-chloro-1h-indazole-3-carbonyl)amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC)CCC1NC(=O)C1=NNC2=CC=C(Cl)C=C12 WVBGCSKNPACHSD-UHFFFAOYSA-N 0.000 claims description 3
- NADYBSKEJNTOBR-UHFFFAOYSA-N n-(1-acetylpiperidin-4-yl)-1h-indazole-3-carboxamide Chemical compound C1CN(C(=O)C)CCC1NC(=O)C1=NNC2=CC=CC=C12 NADYBSKEJNTOBR-UHFFFAOYSA-N 0.000 claims description 3
- SZMBUDSICMSQII-UHFFFAOYSA-N n-(1-methylsulfonylpiperidin-4-yl)-1h-indazole-3-carboxamide Chemical compound C1CN(S(=O)(=O)C)CCC1NC(=O)C1=NNC2=CC=CC=C12 SZMBUDSICMSQII-UHFFFAOYSA-N 0.000 claims description 3
- HNBPWEIBJASQNQ-UHFFFAOYSA-N n-(3-methylsulfonylphenyl)-1h-indazole-3-carboxamide Chemical compound CS(=O)(=O)C1=CC=CC(NC(=O)C=2C3=CC=CC=C3NN=2)=C1 HNBPWEIBJASQNQ-UHFFFAOYSA-N 0.000 claims description 3
- PEWRGQTYIPXGJB-UHFFFAOYSA-N n-(4-fluorophenyl)-5-iodo-1h-indazole-3-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=NNC2=CC=C(I)C=C12 PEWRGQTYIPXGJB-UHFFFAOYSA-N 0.000 claims description 3
- AYACSSSYCLUBSK-UHFFFAOYSA-N n-(4-morpholin-4-ylsulfonylphenyl)-1h-indazole-3-carboxamide Chemical compound N=1NC2=CC=CC=C2C=1C(=O)NC(C=C1)=CC=C1S(=O)(=O)N1CCOCC1 AYACSSSYCLUBSK-UHFFFAOYSA-N 0.000 claims description 3
- MNHPHKFLWAPNOV-UHFFFAOYSA-N n-(4-sulfamoylphenyl)-1h-indazole-3-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC(=O)C1=NNC2=CC=CC=C12 MNHPHKFLWAPNOV-UHFFFAOYSA-N 0.000 claims description 3
- BZHYPYXBDBGOAB-UHFFFAOYSA-N n-(6-chloropyridin-3-yl)-1h-indazole-3-carboxamide Chemical compound C1=NC(Cl)=CC=C1NC(=O)C1=NNC2=CC=CC=C12 BZHYPYXBDBGOAB-UHFFFAOYSA-N 0.000 claims description 3
- GPKBTYRKFHLKHH-UHFFFAOYSA-N n-(6-chloropyridin-3-yl)-5-morpholin-4-yl-1h-indazole-3-carboxamide Chemical compound C1=NC(Cl)=CC=C1NC(=O)C1=NNC2=CC=C(N3CCOCC3)C=C12 GPKBTYRKFHLKHH-UHFFFAOYSA-N 0.000 claims description 3
- CTUYJHHGEYEGEF-UHFFFAOYSA-N n-[3-(2h-tetrazol-5-yl)phenyl]-1h-indazole-3-carboxamide Chemical compound N=1NC2=CC=CC=C2C=1C(=O)NC(C=1)=CC=CC=1C1=NN=NN1 CTUYJHHGEYEGEF-UHFFFAOYSA-N 0.000 claims description 3
- SYYUZSXLTIUZPT-UHFFFAOYSA-N n-[4-(1h-imidazol-5-yl)phenyl]-1h-indazole-3-carboxamide Chemical compound N=1NC2=CC=CC=C2C=1C(=O)NC(C=C1)=CC=C1C1=CNC=N1 SYYUZSXLTIUZPT-UHFFFAOYSA-N 0.000 claims description 3
- XCFHLVXOAGNVGA-UHFFFAOYSA-N n-[4-(2-oxopyrrolidin-1-yl)phenyl]-1h-indazole-3-carboxamide Chemical compound N=1NC2=CC=CC=C2C=1C(=O)NC(C=C1)=CC=C1N1CCCC1=O XCFHLVXOAGNVGA-UHFFFAOYSA-N 0.000 claims description 3
- UZDCCBTWYKNLBN-UHFFFAOYSA-N n-[4-(acetamidomethyl)phenyl]-1h-indazole-3-carboxamide Chemical compound C1=CC(CNC(=O)C)=CC=C1NC(=O)C1=NNC2=CC=CC=C12 UZDCCBTWYKNLBN-UHFFFAOYSA-N 0.000 claims description 3
- URDSYFPIJXAPAN-UHFFFAOYSA-N n-[4-(acetamidomethyl)phenyl]-5-chloro-1h-indazole-3-carboxamide Chemical compound C1=CC(CNC(=O)C)=CC=C1NC(=O)C1=NNC2=CC=C(Cl)C=C12 URDSYFPIJXAPAN-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0218625.2A GB0218625D0 (en) | 2002-08-10 | 2002-08-10 | Pharmaceutical compounds |
| PCT/GB2003/003491 WO2004014864A1 (en) | 2002-08-10 | 2003-08-08 | 1h-indazole-3-carboxamide compounds as cyclin dependent kinases (cdk) inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006500348A true JP2006500348A (ja) | 2006-01-05 |
| JP2006500348A5 JP2006500348A5 (enExample) | 2006-10-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004527053A Pending JP2006500348A (ja) | 2002-08-10 | 2003-08-08 | サイクリン依存キナーゼ(cdk)インヒビターとしての1h−インダゾール−3−カルボキサミド化合物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20060135589A1 (enExample) |
| EP (1) | EP1534685A1 (enExample) |
| JP (1) | JP2006500348A (enExample) |
| AU (1) | AU2003255779A1 (enExample) |
| GB (1) | GB0218625D0 (enExample) |
| WO (1) | WO2004014864A1 (enExample) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006504711A (ja) * | 2002-10-02 | 2006-02-09 | サノフィ−アベンティス | インダゾールカルボキサミド誘導体、それらの製造法ならびにcdk1、cdk2およびcdk4阻害剤としての用途 |
| JP2007501804A (ja) * | 2003-08-08 | 2007-02-01 | バーテックス ファーマシューティカルズ インコーポレイテッド | 電位開口型のナトリウムチャネルのインヒビターとして有用な組成物 |
| JP2009532370A (ja) * | 2006-03-31 | 2009-09-10 | アボット・ラボラトリーズ | インダゾール化合物 |
| JP2014526510A (ja) * | 2011-09-14 | 2014-10-06 | サミュメッド リミテッド ライアビリティ カンパニー | インダゾール−3−カルボキサミドおよびWNT/β−カテニンシグナル伝達経路阻害剤としてのそれらの使用 |
| JP2016509583A (ja) * | 2012-12-21 | 2016-03-31 | プレキシコン インコーポレーテッドPlexxikon Inc. | キナーゼ調節のための化合物および方法、ならびにその適応 |
| JP2020515567A (ja) * | 2017-03-28 | 2020-05-28 | ビーエーエスエフ ソシエタス・ヨーロピアBasf Se | 殺生物剤化合物 |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003276919B2 (en) | 2002-09-25 | 2013-05-16 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
| EP1616862A4 (en) * | 2003-04-18 | 2008-07-16 | Ono Pharmaceutical Co | HETEROCYCLIC NITROGEN COMPOUND AND USE THEREOF |
| NZ544756A (en) | 2003-07-22 | 2009-09-25 | Astex Therapeutics Ltd | 3,4-Disubstituted 1H-pyrazole compounds and their use as cyclin dependent kinases (CDK) and glycogen synthase kinase-3 (GSK-3) modulators |
| WO2005014554A1 (en) * | 2003-08-08 | 2005-02-17 | Astex Therapeutics Limited | 1h-indazole-3-carboxamide compounds as mapkap kinase modulators |
| WO2005063767A2 (en) | 2003-12-22 | 2005-07-14 | Memory Pharmaceuticals Corporation | Indoles, 1h-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof |
| FR2867778B1 (fr) * | 2004-03-16 | 2006-06-09 | Sanofi Synthelabo | Utilisation de derives d'indazolecarboxamides pour la preparation d'un medicament destine au traitement et a la prevention du paludisme |
| US20050234095A1 (en) | 2004-03-25 | 2005-10-20 | Wenge Xie | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| JP2007534692A (ja) | 2004-04-22 | 2007-11-29 | メモリー・ファーマシューティカルズ・コーポレイション | インドール、1h−インダゾール、1,2−ベンズイソキサゾール、1,2−ベンゾイソチアゾール、ならびにその調製および使用 |
| US7632831B2 (en) | 2004-05-07 | 2009-12-15 | Memory Pharmaceuticals Corporation | 1H-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof |
| MX2007004551A (es) | 2004-10-18 | 2007-05-23 | Amgen Inc | Compuestos tiadiazol y metodos de uso. |
| RU2418797C2 (ru) | 2004-12-22 | 2011-05-20 | Мемори Фармасьютиклз Корпорейшн | Лиганды никотинового рецептора альфа-7, их получение и применение |
| AR052559A1 (es) * | 2005-01-21 | 2007-03-21 | Astex Therapeutics Ltd | Derivados de pirazol para inhibir cdk's y gsk's |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
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| JP2006504711A (ja) * | 2002-10-02 | 2006-02-09 | サノフィ−アベンティス | インダゾールカルボキサミド誘導体、それらの製造法ならびにcdk1、cdk2およびcdk4阻害剤としての用途 |
| JP4762543B2 (ja) * | 2002-10-02 | 2011-08-31 | サノフィ−アベンティス | インダゾールカルボキサミド誘導体、それらの製造法ならびにcdk1、cdk2およびcdk4阻害剤としての用途 |
| JP2007501804A (ja) * | 2003-08-08 | 2007-02-01 | バーテックス ファーマシューティカルズ インコーポレイテッド | 電位開口型のナトリウムチャネルのインヒビターとして有用な組成物 |
| JP2009532370A (ja) * | 2006-03-31 | 2009-09-10 | アボット・ラボラトリーズ | インダゾール化合物 |
| JP2014526510A (ja) * | 2011-09-14 | 2014-10-06 | サミュメッド リミテッド ライアビリティ カンパニー | インダゾール−3−カルボキサミドおよびWNT/β−カテニンシグナル伝達経路阻害剤としてのそれらの使用 |
| JP2017036317A (ja) * | 2011-09-14 | 2017-02-16 | サミュメッド リミテッド ライアビリティ カンパニー | インダゾール−3−カルボキサミドおよびWNT/β−カテニンシグナル伝達経路阻害剤としてのそれらの使用 |
| JP2016509583A (ja) * | 2012-12-21 | 2016-03-31 | プレキシコン インコーポレーテッドPlexxikon Inc. | キナーゼ調節のための化合物および方法、ならびにその適応 |
| JP2020515567A (ja) * | 2017-03-28 | 2020-05-28 | ビーエーエスエフ ソシエタス・ヨーロピアBasf Se | 殺生物剤化合物 |
| JP7160486B2 (ja) | 2017-03-28 | 2022-10-25 | ビーエーエスエフ ソシエタス・ヨーロピア | 殺生物剤化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003255779A1 (en) | 2004-02-25 |
| EP1534685A1 (en) | 2005-06-01 |
| GB0218625D0 (en) | 2002-09-18 |
| WO2004014864A1 (en) | 2004-02-19 |
| US20060135589A1 (en) | 2006-06-22 |
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