ES2374449T3 - Compuestos de imidazol sustituidos como inhibidores de ksp. - Google Patents
Compuestos de imidazol sustituidos como inhibidores de ksp. Download PDFInfo
- Publication number
- ES2374449T3 ES2374449T3 ES06789653T ES06789653T ES2374449T3 ES 2374449 T3 ES2374449 T3 ES 2374449T3 ES 06789653 T ES06789653 T ES 06789653T ES 06789653 T ES06789653 T ES 06789653T ES 2374449 T3 ES2374449 T3 ES 2374449T3
- Authority
- ES
- Spain
- Prior art keywords
- benzyl
- phenyl
- amino
- imidazol
- dimethylpropyl
- Prior art date
- 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.)
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- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title description 33
- 239000003112 inhibitor Substances 0.000 title description 11
- -1 carboxyl ester Chemical class 0.000 claims abstract description 276
- 150000001875 compounds Chemical class 0.000 claims abstract description 212
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 145
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 94
- 125000003118 aryl group Chemical group 0.000 claims abstract description 66
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 48
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 42
- 239000001257 hydrogen Substances 0.000 claims abstract description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 37
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 33
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 25
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 21
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 18
- 125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 16
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 14
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 125000004429 atom Chemical group 0.000 claims abstract description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
- 125000005415 substituted alkoxy group Chemical group 0.000 claims abstract description 12
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims abstract description 10
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 120
- 206010028980 Neoplasm Diseases 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 201000011510 cancer Diseases 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 21
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 13
- 239000004202 carbamide Substances 0.000 claims description 13
- STUHQDIOZQUPGP-UHFFFAOYSA-N morpholin-4-ium-4-carboxylate Chemical compound OC(=O)N1CCOCC1 STUHQDIOZQUPGP-UHFFFAOYSA-N 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000002062 proliferating effect Effects 0.000 claims description 5
- 210000004556 brain Anatomy 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
- QEDIQYPGKNETBN-DYKQPOOOSA-N n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-n-[[(3r)-3-fluoropyrrolidin-3-yl]methyl]-4-piperidin-1-ylpiperidine-1-carboxamide Chemical compound C1CC(N2CCCCC2)CCN1C(=O)N([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C[C@@]1(F)CCNC1 QEDIQYPGKNETBN-DYKQPOOOSA-N 0.000 claims description 4
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims description 4
- MYELFCBDZMZCFZ-QFIPXVFZSA-N 1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-1,3-diazinan-2-one Chemical compound N1([C@H](C(C)(C)C)C=2N(C=C(N=2)C=2C=CC=CC=2)CC=2C=CC=CC=2)CCCNC1=O MYELFCBDZMZCFZ-QFIPXVFZSA-N 0.000 claims description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 150000004702 methyl esters Chemical class 0.000 claims description 3
- IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- ZGGXJHGNKKKHOC-CWSACCBASA-N (2r,6s)-n-[(3s)-3-amino-4-fluorobutyl]-n-[(1r)-1-[1-[(3-hydroxyphenyl)methyl]-4-(2,3,5-trifluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-2,6-dimethylmorpholine-4-carboxamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)N(CC[C@H](N)CF)[C@H](C(C)(C)C)C1=NC(C=2C(=C(F)C=C(F)C=2)F)=CN1CC1=CC=CC(O)=C1 ZGGXJHGNKKKHOC-CWSACCBASA-N 0.000 claims description 2
- FAIUWKXDSLBIKT-FFBVMRPSSA-N (2s,6r)-n-[(3r)-3-amino-4-fluorobutyl]-n-[(1r)-1-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-2,6-dimethylmorpholine-4-carboxamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)N(CC[C@@H](N)CF)[C@H](C(C)(C)C)C1=NC(C=2C(=CC=C(F)C=2)F)=CN1CC1=CC=CC=C1 FAIUWKXDSLBIKT-FFBVMRPSSA-N 0.000 claims description 2
- JHYXLHFINQYNSP-CVWIZFJUSA-N (3r)-n-(3-amino-2-fluoropropyl)-n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide Chemical compound NCC(F)CN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)N1CCC[C@@H](O)C1 JHYXLHFINQYNSP-CVWIZFJUSA-N 0.000 claims description 2
- AXZRSNIRYBQWBV-VPUSJEBWSA-N (3r)-n-(3-aminopropyl)-n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide Chemical compound NCCCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)N1CCC[C@@H](O)C1 AXZRSNIRYBQWBV-VPUSJEBWSA-N 0.000 claims description 2
- YRIWIRWRACZCEV-WEWMWRJBSA-N (3r)-n-[(3s)-3-amino-4-hydroxybutyl]-n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound OC[C@@H](N)CCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)N1CC[C@@H](O)C1 YRIWIRWRACZCEV-WEWMWRJBSA-N 0.000 claims description 2
- AXZRSNIRYBQWBV-BDYUSTAISA-N (3s)-n-(3-aminopropyl)-n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide Chemical compound NCCCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)N1CCC[C@H](O)C1 AXZRSNIRYBQWBV-BDYUSTAISA-N 0.000 claims description 2
- GEBYXLCXSRCDDD-AHWVRZQESA-N (3s)-n-(3-aminopropyl)-n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound NCCCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)N1CC[C@H](O)C1 GEBYXLCXSRCDDD-AHWVRZQESA-N 0.000 claims description 2
- JXADZOUBCXDJMD-WCYRKSIYSA-N (3s)-n-[(3s)-3-amino-4-fluorobutyl]-n-[(1r)-1-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound FC[C@@H](N)CCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C(=CC=C(F)C=1)F)CC=1C=CC=CC=1)C(=O)N1CC[C@H](O)C1 JXADZOUBCXDJMD-WCYRKSIYSA-N 0.000 claims description 2
- ACBMLNDOSAGHMQ-OYRHQHFDSA-N (4r)-n-[(2r)-3-amino-2-fluoropropyl]-n-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-4-hydroxy-1,2-oxazolidine-2-carboxamide Chemical compound NC[C@@H](F)CN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)N1C[C@@H](O)CO1 ACBMLNDOSAGHMQ-OYRHQHFDSA-N 0.000 claims description 2
- RZXWYROYFAABBQ-VWLOTQADSA-N 1-(3-amino-3-methylbutyl)-1-[(1r)-1-[1-benzyl-4-(3-fluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-3,3-dimethylurea Chemical compound CC(N)(C)CCN(C(=O)N(C)C)[C@H](C(C)(C)C)C1=NC(C=2C=C(F)C=CC=2)=CN1CC1=CC=CC=C1 RZXWYROYFAABBQ-VWLOTQADSA-N 0.000 claims description 2
- UHUXHUKWWQFRCE-DEOSSOPVSA-N 1-(3-amino-3-methylbutyl)-1-[(1r)-1-[1-benzyl-4-(3-fluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-3-methylurea Chemical compound CC(N)(C)CCN(C(=O)NC)[C@H](C(C)(C)C)C1=NC(C=2C=C(F)C=CC=2)=CN1CC1=CC=CC=C1 UHUXHUKWWQFRCE-DEOSSOPVSA-N 0.000 claims description 2
- UOJMAYSKJKNYQX-QHCPKHFHSA-N 1-(3-amino-3-methylbutyl)-1-[(1r)-1-[1-benzyl-4-(3-fluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]urea Chemical compound CC(C)(N)CCN(C(N)=O)[C@H](C(C)(C)C)C1=NC(C=2C=C(F)C=CC=2)=CN1CC1=CC=CC=C1 UOJMAYSKJKNYQX-QHCPKHFHSA-N 0.000 claims description 2
- JHUBDJRPIBVVOT-DEOSSOPVSA-N 1-(3-aminopropyl)-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3,3-dimethylurea Chemical compound NCCCN(C(=O)N(C)C)[C@H](C(C)(C)C)C1=NC(C=2C=CC=CC=2)=CN1CC1=CC=CC=C1 JHUBDJRPIBVVOT-DEOSSOPVSA-N 0.000 claims description 2
- CMVBTIQUWLAFGG-VWLOTQADSA-N 1-(3-aminopropyl)-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(2-methoxyethyl)urea Chemical compound COCCNC(=O)N(CCCN)[C@H](C(C)(C)C)C1=NC(C=2C=CC=CC=2)=CN1CC1=CC=CC=C1 CMVBTIQUWLAFGG-VWLOTQADSA-N 0.000 claims description 2
- GVROZXWSBGMVFV-LJAQVGFWSA-N 1-(3-aminopropyl)-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(4-cyanophenyl)urea Chemical compound NCCCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)NC1=CC=C(C#N)C=C1 GVROZXWSBGMVFV-LJAQVGFWSA-N 0.000 claims description 2
- DZFBZDXQJDMOQL-MHZLTWQESA-N 1-(3-aminopropyl)-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(furan-2-ylmethyl)urea Chemical compound NCCCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)NCC1=CC=CO1 DZFBZDXQJDMOQL-MHZLTWQESA-N 0.000 claims description 2
- QQIWLVZSEFYAKN-QFIPXVFZSA-N 1-(3-aminopropyl)-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-hydroxyurea Chemical compound NCCCN(C(=O)NO)[C@H](C(C)(C)C)C1=NC(C=2C=CC=CC=2)=CN1CC1=CC=CC=C1 QQIWLVZSEFYAKN-QFIPXVFZSA-N 0.000 claims description 2
- KAYKZMXGMYYSGB-NDEPHWFRSA-N 1-(3-aminopropyl)-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-phenylurea Chemical compound NCCCN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)NC1=CC=CC=C1 KAYKZMXGMYYSGB-NDEPHWFRSA-N 0.000 claims description 2
- PVYDRBCTJXWSNM-DEOSSOPVSA-N 1-(3-aminopropyl)-1-[(1r)-1-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-3,3-dimethylurea Chemical compound NCCCN(C(=O)N(C)C)[C@H](C(C)(C)C)C1=NC(C=2C(=CC=C(F)C=2)F)=CN1CC1=CC=CC=C1 PVYDRBCTJXWSNM-DEOSSOPVSA-N 0.000 claims description 2
- NESJORCGJBAFKO-MHZLTWQESA-N 1-(3-aminopropyl)-1-[(1r)-1-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-3-(3,5-dimethyl-1,2-oxazol-4-yl)urea Chemical compound CC1=NOC(C)=C1NC(=O)N(CCCN)[C@H](C(C)(C)C)C1=NC(C=2C(=CC=C(F)C=2)F)=CN1CC1=CC=CC=C1 NESJORCGJBAFKO-MHZLTWQESA-N 0.000 claims description 2
- RVDVXHZKWMWYEP-QHCPKHFHSA-N 1-(3-aminopropyl)-1-[(1r)-1-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-3-methylurea Chemical compound NCCCN(C(=O)NC)[C@H](C(C)(C)C)C1=NC(C=2C(=CC=C(F)C=2)F)=CN1CC1=CC=CC=C1 RVDVXHZKWMWYEP-QHCPKHFHSA-N 0.000 claims description 2
- PKAHTZGPEBWADF-NGQVCNFZSA-N 1-[(1r)-1-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-2,2-dimethylpropyl]-1-[(3s)-3-(1,3-dioxoisoindol-2-yl)-4-fluorobutyl]-3-methylurea Chemical compound C1([C@H](N(CC[C@@H](CF)N2C(C3=CC=CC=C3C2=O)=O)C(=O)NC)C(C)(C)C)=NC(C=2C(=CC=C(F)C=2)F)=CN1CC1=CC=CC=C1 PKAHTZGPEBWADF-NGQVCNFZSA-N 0.000 claims description 2
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- DWRXANOIMWBODT-NOZRDPDXSA-N 1-[(2r)-3-amino-2-fluoropropyl]-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(2-methoxyethyl)urea Chemical compound COCCNC(=O)N(C[C@H](F)CN)[C@H](C(C)(C)C)C1=NC(C=2C=CC=CC=2)=CN1CC1=CC=CC=C1 DWRXANOIMWBODT-NOZRDPDXSA-N 0.000 claims description 2
- NVCALJIXJGLXDS-LXFBAYGMSA-N 1-[(2r)-3-amino-2-fluoropropyl]-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(3,4-difluorophenyl)urea Chemical compound NC[C@@H](F)CN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)NC1=CC=C(F)C(F)=C1 NVCALJIXJGLXDS-LXFBAYGMSA-N 0.000 claims description 2
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- DRQWOIWQLWVPNS-ZCYQVOJMSA-N 1-[(2s)-3-amino-2-fluoropropyl]-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(2-hydroxyethyl)-3-methylurea Chemical compound OCCN(C)C(=O)N(C[C@@H](F)CN)[C@H](C(C)(C)C)C1=NC(C=2C=CC=CC=2)=CN1CC1=CC=CC=C1 DRQWOIWQLWVPNS-ZCYQVOJMSA-N 0.000 claims description 2
- FBBVYHJYFRJSFO-WNJJXGMVSA-N 1-[(2s)-3-amino-2-fluoropropyl]-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-(4-cyanophenyl)urea Chemical compound NC[C@H](F)CN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)NC1=CC=C(C#N)C=C1 FBBVYHJYFRJSFO-WNJJXGMVSA-N 0.000 claims description 2
- JZHHUYAASSIIBG-LSYYVWMOSA-N 1-[(2s)-3-amino-2-fluoropropyl]-1-[(1r)-1-(1-benzyl-4-phenylimidazol-2-yl)-2,2-dimethylpropyl]-3-phenylurea Chemical compound NC[C@H](F)CN([C@H](C(C)(C)C)C=1N(C=C(N=1)C=1C=CC=CC=1)CC=1C=CC=CC=1)C(=O)NC1=CC=CC=C1 JZHHUYAASSIIBG-LSYYVWMOSA-N 0.000 claims description 2
- PRXTZIHOAREPRY-UNMCSNQZSA-N 1-[(2s)-3-amino-2-fluoropropyl]-1-[(1r)-1-[4-(3-fluorophenyl)-1-[(3-fluorophenyl)methyl]imidazol-2-yl]-2,2-dimethylpropyl]urea Chemical compound NC[C@H](F)CN(C(N)=O)[C@H](C(C)(C)C)C1=NC(C=2C=C(F)C=CC=2)=CN1CC1=CC=CC(F)=C1 PRXTZIHOAREPRY-UNMCSNQZSA-N 0.000 claims description 2
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Classifications
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- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/12—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
- C07D409/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70690105P | 2005-08-09 | 2005-08-09 | |
| US706901P | 2005-08-09 | ||
| PCT/US2006/031129 WO2007021794A1 (en) | 2005-08-09 | 2006-08-09 | Substituted imidazole compounds as ksp inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2374449T3 true ES2374449T3 (es) | 2012-02-16 |
Family
ID=37421032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06789653T Active ES2374449T3 (es) | 2005-08-09 | 2006-08-09 | Compuestos de imidazol sustituidos como inhibidores de ksp. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7626040B2 (https=) |
| EP (1) | EP1912972B1 (https=) |
| JP (1) | JP4975745B2 (https=) |
| KR (1) | KR20080036611A (https=) |
| CN (1) | CN101253167A (https=) |
| AR (1) | AR056025A1 (https=) |
| AT (1) | ATE526324T1 (https=) |
| AU (1) | AU2006279991B2 (https=) |
| BR (1) | BRPI0614547A2 (https=) |
| CA (1) | CA2618747A1 (https=) |
| ES (1) | ES2374449T3 (https=) |
| GT (1) | GT200600366A (https=) |
| MY (1) | MY147188A (https=) |
| PE (1) | PE20070352A1 (https=) |
| PL (1) | PL1912972T3 (https=) |
| PT (1) | PT1912972E (https=) |
| RU (1) | RU2413721C9 (https=) |
| TW (1) | TW200800951A (https=) |
| WO (1) | WO2007021794A1 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2007323998B2 (en) * | 2006-11-13 | 2011-09-22 | Novartis Ag | Substituted pyrazole and triazole compounds as KSP inhibitors |
| AU2008205169B2 (en) * | 2007-01-05 | 2012-02-02 | Novartis Ag | Imidazole derivatives as kinesin spindle protein inhibitors (Eg-5) |
| AR068888A1 (es) | 2007-10-19 | 2009-12-16 | Schering Corp | Derivados de 1, 3, 4 - tiadiazol, una composicion farmaceutica que los comprende y su uso en la preparacion de medicamentos para el tratamiento de enfermedades mediadas por la inhibicion de la quinesina ksp. |
| US8252832B2 (en) * | 2007-12-14 | 2012-08-28 | Novartis Ag | Kinesin inhibitors as cancer therapeutics |
| JP2013523867A (ja) | 2010-04-15 | 2013-06-17 | ノバルティス アーゲー | Ｋｓｐ阻害剤としてのトリアゾール化合物 |
| US9498540B2 (en) | 2013-03-15 | 2016-11-22 | Novartis Ag | Cell proliferation inhibitors and conjugates thereof |
| EP2968591A1 (en) * | 2013-03-15 | 2016-01-20 | Novartis AG | Cell proliferation inhibitors and conjugates thereof |
| PL3086814T3 (pl) * | 2013-12-23 | 2020-12-28 | Bayer Pharma Aktiengesellschaft | Koniugaty środka wiążącego (ADC) z inhibitorami KSP |
| US10786578B2 (en) | 2014-08-05 | 2020-09-29 | Novartis Ag | CKIT antibody drug conjugates |
| RU2751512C2 (ru) * | 2015-06-22 | 2021-07-14 | Байер Фарма Акциенгезельшафт | Конъюгаты антитела и лекарственного средства (adc) и конъюгаты антитела и пролекарства (apdc), содержащие ферментативно расщепляемые группы |
| JP6768011B2 (ja) * | 2015-06-23 | 2020-10-14 | バイエル ファーマ アクチエンゲゼルシャフト | キネシンスピンドルタンパク質（ｋｓｐ）阻害剤の抗ｃｄ１２３抗体との抗体薬物複合体 |
| WO2017216028A1 (en) | 2016-06-15 | 2017-12-21 | Bayer Pharma Aktiengesellschaft | Specific antibody-drug-conjugates (adcs) with ksp inhibitors and anti-cd123-antibodies |
| JP7066714B2 (ja) | 2016-12-21 | 2022-05-13 | バイエル・ファルマ・アクティエンゲゼルシャフト | 酵素的に切断可能な基を有する抗体薬物コンジュゲート（ａｄｃ） |
| JP7030811B2 (ja) | 2016-12-21 | 2022-03-07 | バイエル・ファルマ・アクティエンゲゼルシャフト | Ｋｓｐ阻害剤を有する特異的抗体－薬物コンジュゲート（ａｄｃ） |
| JP2021527640A (ja) | 2018-06-18 | 2021-10-14 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 酵素的に切断可能なリンカーおよび改善された活性プロファイルを有する、ｃｘｃｒ５に対して向けられるバインダー／活性薬剤複合体 |
| CN109481436A (zh) * | 2018-08-21 | 2019-03-19 | 广东医科大学 | 血栓素a2合成酶抑制剂奥扎格雷在制备治疗吸烟所致肺癌药物中的应用 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5011472A (en) | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
| EP0946587A2 (en) | 1996-12-16 | 1999-10-06 | Fujisawa Pharmaceutical Co., Ltd. | New amide compounds |
| US6117940A (en) | 1997-10-17 | 2000-09-12 | Mjalli; Adnan M. M. | Amino-ketone solid support templates |
| US6852725B1 (en) * | 1998-06-12 | 2005-02-08 | Societe De Conseils De Recherches Et D'applications Scientifiques, S. A. S. | Imidazolyl derivatives |
| ATE327224T1 (de) * | 1999-10-27 | 2006-06-15 | Cytokinetics Inc | Chinazolinone benutzende verfahren und zusammenstellungen |
| US6545004B1 (en) * | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| US6620882B1 (en) | 2000-05-02 | 2003-09-16 | Advanced Syntech, Llc | Solid support template for preparation of highly functionalized heterocycle compounds |
| WO2002010140A2 (en) * | 2000-08-01 | 2002-02-07 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Imidazolyl derivatives |
| US7026312B2 (en) * | 2002-03-14 | 2006-04-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Substituted piperidines, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
| DE10211770A1 (de) | 2002-03-14 | 2003-10-02 | Boehringer Ingelheim Pharma | Neue substituierte Piperidine, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| RU2005100783A (ru) * | 2002-06-14 | 2005-07-20 | Мерк энд Ко., Инк. (US) | Ингибиторы митотического кинезина |
| WO2004071448A2 (en) | 2003-02-12 | 2004-08-26 | Transtech Pharma Inc. | Substituted azole derivatives as inhibitors of protein tyrosine phosphatases |
| EP1620092A4 (en) * | 2003-05-07 | 2008-04-16 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| EP1622878A4 (en) * | 2003-05-15 | 2008-04-09 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| WO2005100322A1 (en) | 2004-04-14 | 2005-10-27 | Pfizer Limited | Sulphur-linked imidazole compounds for the treament of hiv |
| US7618981B2 (en) | 2004-05-06 | 2009-11-17 | Cytokinetics, Inc. | Imidazopyridinyl-benzamide anti-cancer agents |
| KR101170925B1 (ko) * | 2004-06-18 | 2012-08-07 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 암 치료용 키네신 방추 단백질 (ｋｓｐ) 억제제로서의ｎ-(1-(1-벤질-4-페닐-1ｈ-이미다졸-2-일)-2,2-디메틸프로필)벤자미드 유도체 및 관련 화합물 |
-
2006
- 2006-08-08 TW TW095129062A patent/TW200800951A/zh unknown
- 2006-08-08 MY MYPI20063824A patent/MY147188A/en unknown
- 2006-08-09 JP JP2008526175A patent/JP4975745B2/ja not_active Expired - Fee Related
- 2006-08-09 BR BRPI0614547-7A patent/BRPI0614547A2/pt not_active IP Right Cessation
- 2006-08-09 GT GT200600366A patent/GT200600366A/es unknown
- 2006-08-09 RU RU2008108939/04A patent/RU2413721C9/ru not_active IP Right Cessation
- 2006-08-09 KR KR1020087003946A patent/KR20080036611A/ko not_active Ceased
- 2006-08-09 AU AU2006279991A patent/AU2006279991B2/en not_active Ceased
- 2006-08-09 ES ES06789653T patent/ES2374449T3/es active Active
- 2006-08-09 AT AT06789653T patent/ATE526324T1/de active
- 2006-08-09 AR ARP060103489A patent/AR056025A1/es not_active Application Discontinuation
- 2006-08-09 EP EP06789653A patent/EP1912972B1/en active Active
- 2006-08-09 CN CNA2006800293472A patent/CN101253167A/zh active Pending
- 2006-08-09 PE PE2006000968A patent/PE20070352A1/es not_active Application Discontinuation
- 2006-08-09 WO PCT/US2006/031129 patent/WO2007021794A1/en not_active Ceased
- 2006-08-09 CA CA002618747A patent/CA2618747A1/en not_active Abandoned
- 2006-08-09 US US11/502,303 patent/US7626040B2/en not_active Expired - Fee Related
- 2006-08-09 PT PT06789653T patent/PT1912972E/pt unknown
- 2006-08-09 PL PL06789653T patent/PL1912972T3/pl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200800951A (en) | 2008-01-01 |
| JP4975745B2 (ja) | 2012-07-11 |
| WO2007021794A1 (en) | 2007-02-22 |
| US20070037853A1 (en) | 2007-02-15 |
| US7626040B2 (en) | 2009-12-01 |
| RU2008108939A (ru) | 2009-09-20 |
| CN101253167A (zh) | 2008-08-27 |
| PT1912972E (pt) | 2012-01-06 |
| ATE526324T1 (de) | 2011-10-15 |
| BRPI0614547A2 (pt) | 2011-03-29 |
| CA2618747A1 (en) | 2007-02-22 |
| AU2006279991A1 (en) | 2007-02-22 |
| GT200600366A (es) | 2007-05-10 |
| PE20070352A1 (es) | 2007-05-30 |
| HK1111995A1 (en) | 2008-08-22 |
| JP2009504664A (ja) | 2009-02-05 |
| AU2006279991B2 (en) | 2011-09-29 |
| EP1912972A1 (en) | 2008-04-23 |
| KR20080036611A (ko) | 2008-04-28 |
| EP1912972B1 (en) | 2011-09-28 |
| PL1912972T3 (pl) | 2012-02-29 |
| MY147188A (en) | 2012-11-14 |
| AR056025A1 (es) | 2007-09-12 |
| RU2413721C2 (ru) | 2011-03-10 |
| RU2413721C9 (ru) | 2011-05-20 |
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