HRP20010142A2 - Alkynyl-substituted quinolin-2-one derivatives useful as anticancer agents - Google Patents

Info

Publication number

HRP20010142A2

HRP20010142A2 HR20010142A HRP20010142A HRP20010142A2 HR P20010142 A2 HRP20010142 A2 HR P20010142A2 HR 20010142 A HR20010142 A HR 20010142A HR P20010142 A HRP20010142 A HR P20010142A HR P20010142 A2 HRP20010142 A2 HR P20010142A2

Authority

HR

Croatia

Prior art keywords

methyl

cr13r14

phenyl

aryl

cancer

Prior art date

1998-08-27

Links

• Espacenet
• Global Dossier
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• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title claims description 10
• 239000002246 antineoplastic agent Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims description 157
• 125000000623 heterocyclic group Chemical group 0.000 claims description 49
• 238000000034 method Methods 0.000 claims description 44
• -1 hydroxy, amino Chemical group 0.000 claims description 34
• 238000006243 chemical reaction Methods 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 32
• 125000001424 substituent group Chemical group 0.000 claims description 32
• 230000002159 abnormal effect Effects 0.000 claims description 28
• 230000010261 cell growth Effects 0.000 claims description 28
• 241000124008 Mammalia Species 0.000 claims description 27
• 206010028980 Neoplasm Diseases 0.000 claims description 25
• 239000000651 prodrug Substances 0.000 claims description 24
• 229940002612 prodrug Drugs 0.000 claims description 24
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 21
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 125000004122 cyclic group Chemical group 0.000 claims description 14
• 125000002883 imidazolyl group Chemical group 0.000 claims description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 12
• 125000000217 alkyl group Chemical class 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• 239000003112 inhibitor Substances 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 10
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 9
• 125000001425 triazolyl group Chemical group 0.000 claims description 9
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
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• 208000015181 infectious disease Diseases 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 8
• 101000869592 Daucus carota Major allergen Dau c 1 Proteins 0.000 claims description 7
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• 230000002062 proliferating effect Effects 0.000 claims description 7
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• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 239000000126 substance Substances 0.000 claims description 6
• 239000002168 alkylating agent Substances 0.000 claims description 5
• 229940100198 alkylating agent Drugs 0.000 claims description 5
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• XOCYZTBVPWPFDX-UHFFFAOYSA-N 6-(4-chlorobenzoyl)-1-(cyclopropylmethyl)-4-[3-(2-trimethylsilylethynyl)phenyl]quinolin-2-one Chemical compound C[Si](C)(C)C#CC1=CC=CC(C=2C3=CC(=CC=C3N(CC3CC3)C(=O)C=2)C(=O)C=2C=CC(Cl)=CC=2)=C1 XOCYZTBVPWPFDX-UHFFFAOYSA-N 0.000 claims description 4
• JSSNOQBELYYHHH-UHFFFAOYSA-N 6-[(4-chlorophenyl)-hydroxy-(3-methyl-2-sulfanylidene-1h-imidazol-4-yl)methyl]-1-methyl-4-[3-(2-trimethylsilylethynyl)phenyl]quinolin-2-one Chemical compound CN1C(S)=NC=C1C(O)(C=1C=C2C(C=3C=C(C=CC=3)C#C[Si](C)(C)C)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 JSSNOQBELYYHHH-UHFFFAOYSA-N 0.000 claims description 4
• QRYVYKUEXCETRW-UHFFFAOYSA-N 6-[(4-chlorophenyl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-ethynyl-4-fluorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(C(F)=CC=3)C#C)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 QRYVYKUEXCETRW-UHFFFAOYSA-N 0.000 claims description 4
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• 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
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• 208000023915 Ureteral Neoplasms Diseases 0.000 claims description 4
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• 230000000340 anti-metabolite Effects 0.000 claims description 4
• 239000000051 antiandrogen Substances 0.000 claims description 4
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 4
• 239000002256 antimetabolite Substances 0.000 claims description 4
• 229940100197 antimetabolite Drugs 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 208000024207 chronic leukemia Diseases 0.000 claims description 4
• 208000030381 cutaneous melanoma Diseases 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 239000003102 growth factor Substances 0.000 claims description 4
• 239000000367 immunologic factor Substances 0.000 claims description 4
• 239000012444 intercalating antibiotic Substances 0.000 claims description 4
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• 201000004792 malaria Diseases 0.000 claims description 4
• 230000011278 mitosis Effects 0.000 claims description 4
• 201000002575 ocular melanoma Diseases 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
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• 208000037803 restenosis Diseases 0.000 claims description 4
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• 206010062261 spinal cord neoplasm Diseases 0.000 claims description 4
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• RNYNUUHEMGOZRW-UHFFFAOYSA-N 6-(4-chlorobenzoyl)-4-(2-ethynyl-3-trimethylsilylphenyl)-1-methylquinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(C(=O)C=3C=CC(Cl)=CC=3)C=C2C=1C1=CC=CC([Si](C)(C)C)=C1C#C RNYNUUHEMGOZRW-UHFFFAOYSA-N 0.000 claims description 3
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• ZHEXQJWSYFBWJT-UHFFFAOYSA-N 6-(4-chlorobenzoyl)-1-methyl-4-[3-(4-trityloxybut-1-ynyl)phenyl]quinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(C(=O)C=3C=CC(Cl)=CC=3)C=C2C=1C(C=1)=CC=CC=1C#CCCOC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZHEXQJWSYFBWJT-UHFFFAOYSA-N 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 10
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 2
• 208000017897 Carcinoma of esophagus Diseases 0.000 claims 2
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• 206010029148 Nephrolithiasis Diseases 0.000 claims 2
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• 210000000988 bone and bone Anatomy 0.000 claims 2
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• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 claims 1
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
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