AU2005258135B2 - N- (1- (1-benzyl -4-phenyl-1H-imidazol-2-YL) -2,2-dymethylpropyl) benzamide derivatives and related compounds as kinesin spindle protein (KSP) inhibitors for the treatment of cancer - Google Patents
N- (1- (1-benzyl -4-phenyl-1H-imidazol-2-YL) -2,2-dymethylpropyl) benzamide derivatives and related compounds as kinesin spindle protein (KSP) inhibitors for the treatment of cancer Download PDFInfo
- Publication number
- AU2005258135B2 AU2005258135B2 AU2005258135A AU2005258135A AU2005258135B2 AU 2005258135 B2 AU2005258135 B2 AU 2005258135B2 AU 2005258135 A AU2005258135 A AU 2005258135A AU 2005258135 A AU2005258135 A AU 2005258135A AU 2005258135 B2 AU2005258135 B2 AU 2005258135B2
- Authority
- AU
- Australia
- Prior art keywords
- imidazol
- benzyl
- phenyl
- propyl
- amino
- 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.)
- Ceased
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- -1 1-benzyl -4-phenyl-1H-imidazol-2-YL Chemical class 0.000 title claims abstract description 463
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 55
- 201000011510 cancer Diseases 0.000 title claims abstract description 32
- 238000011282 treatment Methods 0.000 title claims abstract description 26
- 150000001875 compounds Chemical class 0.000 title claims description 281
- 102000010638 Kinesin Human genes 0.000 title claims description 9
- 108010063296 Kinesin Proteins 0.000 title claims description 9
- 239000003112 inhibitor Substances 0.000 title description 11
- 108090000623 proteins and genes Proteins 0.000 title description 10
- 102000004169 proteins and genes Human genes 0.000 title description 9
- 150000003936 benzamides Chemical class 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 193
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 159
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 107
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 102
- 239000001257 hydrogen Substances 0.000 claims abstract description 98
- 125000003118 aryl group Chemical group 0.000 claims abstract description 84
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 80
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 77
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 75
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 71
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 55
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 45
- 125000001424 substituent group Chemical group 0.000 claims abstract description 44
- 125000005415 substituted alkoxy group Chemical group 0.000 claims abstract description 41
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 40
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 33
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims abstract description 21
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 312
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 233
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 232
- 239000000203 mixture Substances 0.000 claims description 143
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 94
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 71
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 60
- 125000005843 halogen group Chemical group 0.000 claims description 55
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 48
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- 150000002148 esters Chemical class 0.000 claims description 42
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 150000001412 amines Chemical class 0.000 claims description 36
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 35
- MTEZLAATISORQK-UHFFFAOYSA-N 2-methoxyacetamide Chemical compound COCC(N)=O MTEZLAATISORQK-UHFFFAOYSA-N 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- UJJLJRQIPMGXEZ-BYPYZUCNSA-N (2s)-oxolane-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCO1 UJJLJRQIPMGXEZ-BYPYZUCNSA-N 0.000 claims description 30
- 125000004104 aryloxy group Chemical group 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 27
- 125000002252 acyl group Chemical group 0.000 claims description 26
- 125000003342 alkenyl group Chemical group 0.000 claims description 24
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 150000001721 carbon Chemical group 0.000 claims description 16
- 150000003857 carboxamides Chemical class 0.000 claims description 15
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 14
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- UHBGYFCCKRAEHA-UHFFFAOYSA-N P-toluamide Chemical compound CC1=CC=C(C(N)=O)C=C1 UHBGYFCCKRAEHA-UHFFFAOYSA-N 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 11
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 229960000575 trastuzumab Drugs 0.000 claims description 10
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 9
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 9
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 9
- 210000000244 kidney pelvis Anatomy 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 7
- 230000002062 proliferating effect Effects 0.000 claims description 7
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical compound NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 6
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 claims description 6
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 6
- 210000004556 brain Anatomy 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 6
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 6
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 5
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 5
- 229930012538 Paclitaxel Natural products 0.000 claims description 5
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 5
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 5
- 229960004562 carboplatin Drugs 0.000 claims description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 5
- 229960004316 cisplatin Drugs 0.000 claims description 5
- 210000001072 colon Anatomy 0.000 claims description 5
- 229960004397 cyclophosphamide Drugs 0.000 claims description 5
- 229960003668 docetaxel Drugs 0.000 claims description 5
- 229960002949 fluorouracil Drugs 0.000 claims description 5
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims description 5
- 235000008191 folinic acid Nutrition 0.000 claims description 5
- 239000011672 folinic acid Substances 0.000 claims description 5
- 229960005277 gemcitabine Drugs 0.000 claims description 5
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 5
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 5
- 229960002411 imatinib Drugs 0.000 claims description 5
- 229960004768 irinotecan Drugs 0.000 claims description 5
- 229960001691 leucovorin Drugs 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 235000005152 nicotinamide Nutrition 0.000 claims description 5
- 239000011570 nicotinamide Substances 0.000 claims description 5
- 229960003966 nicotinamide Drugs 0.000 claims description 5
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- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 229960004641 rituximab Drugs 0.000 claims description 5
- 210000002784 stomach Anatomy 0.000 claims description 5
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 5
- 229950006410 tezacitabine Drugs 0.000 claims description 5
- GFFXZLZWLOBBLO-ASKVSEFXSA-N tezacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-ASKVSEFXSA-N 0.000 claims description 5
- 229960000303 topotecan Drugs 0.000 claims description 5
- LZPCOLGNVXYJMS-UHFFFAOYSA-N 1-benzyl-6-(1-benzyl-4-phenylimidazol-2-yl)piperidin-2-one Chemical compound O=C1CCCC(C=2N(C=C(N=2)C=2C=CC=CC=2)CC=2C=CC=CC=2)N1CC1=CC=CC=C1 LZPCOLGNVXYJMS-UHFFFAOYSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- 206010048832 Colon adenoma Diseases 0.000 claims description 4
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 210000000621 bronchi Anatomy 0.000 claims description 4
- 210000003679 cervix uteri Anatomy 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- RHJVIGLEIFVHIJ-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1[CH]CCCC1 RHJVIGLEIFVHIJ-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 4
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- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 3
- STDAKZWKFBEQBX-UHFFFAOYSA-N 1,3-diazaspiro[4.4]nonan-2-one Chemical compound N1C(=O)NCC11CCCC1 STDAKZWKFBEQBX-UHFFFAOYSA-N 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
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- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
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Classifications
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- 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
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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
- 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
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- 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
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/24—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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| EP2106399A2 (en) * | 2007-01-05 | 2009-10-07 | Novartis AG | Imidazole derivatives as kinesin spindle protein inhibitors (eg-5) |
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| WO2014151030A1 (en) * | 2013-03-15 | 2014-09-25 | Novartis Ag | Cell proliferation inhibitors and conjugates thereof |
| US9498540B2 (en) | 2013-03-15 | 2016-11-22 | Novartis Ag | Cell proliferation inhibitors and conjugates thereof |
| JP6721507B2 (ja) * | 2013-12-23 | 2020-07-15 | バイエル・ファルマ・アクティエンゲゼルシャフト | Ksp阻害剤との抗体薬物複合体(adc) |
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| MX2019007641A (es) | 2016-12-21 | 2019-09-09 | Bayer Pharma AG | Conjugados de ligando-farmaco (adcs) con grupos escindibles enzimaticamente. |
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2006002236A1 (en) | 2006-01-05 |
| KR20070106961A (ko) | 2007-11-06 |
| EP1765789A1 (en) | 2007-03-28 |
| NO20070343L (no) | 2007-03-05 |
| JP4836280B2 (ja) | 2011-12-14 |
| BRPI0510929A (pt) | 2007-07-17 |
| MA28739B1 (fr) | 2007-07-02 |
| TW200612958A (en) | 2006-05-01 |
| EP1765789B1 (en) | 2013-02-27 |
| SG153851A1 (en) | 2009-07-29 |
| CA2571002A1 (en) | 2006-01-05 |
| ECSP077183A (es) | 2007-02-28 |
| IL180147A0 (en) | 2007-06-03 |
| US20130017196A1 (en) | 2013-01-17 |
| US20060009472A1 (en) | 2006-01-12 |
| NZ552510A (en) | 2010-12-24 |
| CN1993331A (zh) | 2007-07-04 |
| ZA200700481B (en) | 2008-10-29 |
| US8735599B2 (en) | 2014-05-27 |
| AU2005258135A1 (en) | 2006-01-05 |
| RU2007101612A (ru) | 2008-08-10 |
| JP2011256197A (ja) | 2011-12-22 |
| ES2409345T3 (es) | 2013-06-26 |
| US7576221B2 (en) | 2009-08-18 |
| JP2008503501A (ja) | 2008-02-07 |
| US20090258016A1 (en) | 2009-10-15 |
| TNSN06419A1 (en) | 2008-02-22 |
| KR101170925B1 (ko) | 2012-08-07 |
| US8318791B2 (en) | 2012-11-27 |
| MXPA06014909A (es) | 2007-02-28 |
| RU2427572C2 (ru) | 2011-08-27 |
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