JP4090200B2 - 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 - Google Patents
抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 Download PDFInfo
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- JP4090200B2 JP4090200B2 JP2000598494A JP2000598494A JP4090200B2 JP 4090200 B2 JP4090200 B2 JP 4090200B2 JP 2000598494 A JP2000598494 A JP 2000598494A JP 2000598494 A JP2000598494 A JP 2000598494A JP 4090200 B2 JP4090200 B2 JP 4090200B2
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- Prior art keywords
- methyl
- chloro
- aryl
- alkyl
- phenyl
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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 23
- 239000002246 antineoplastic agent Substances 0.000 title description 10
- 229940041181 antineoplastic drug Drugs 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 317
- 125000000623 heterocyclic group Chemical group 0.000 claims description 196
- 125000001424 substituent group Chemical group 0.000 claims description 118
- 125000003118 aryl group Chemical group 0.000 claims description 93
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 75
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 74
- 125000005843 halogen group Chemical group 0.000 claims description 74
- -1 hydroxy, amino Chemical group 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 53
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 53
- BPXYEYJNCXITEY-UHFFFAOYSA-N diazonio(trifluoromethoxy)azanide Chemical compound FC(F)(F)ON=[N+]=[N-] BPXYEYJNCXITEY-UHFFFAOYSA-N 0.000 claims description 43
- 125000004122 cyclic group Chemical group 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000002883 imidazolyl group Chemical group 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 22
- 239000012453 solvate Substances 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- CNVJCMJNCGMEIG-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1-(cyclopropylmethyl)quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(CC3CC3)C2=CC=1)C1=CC=C(Cl)N=C1 CNVJCMJNCGMEIG-UHFFFAOYSA-N 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- NODWGCWNHFSPFP-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(5-chloropyridin-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1N=CC(Cl)=CC=1)C1=CC=C(N(C)C(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 NODWGCWNHFSPFP-UHFFFAOYSA-N 0.000 claims description 4
- VXTDNGFVFBFDAK-UHFFFAOYSA-N 6-[amino-(6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-(cyclopropylmethyl)quinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(CC3CC3)C2=CC=1)C1=CC=C(Cl)N=C1 VXTDNGFVFBFDAK-UHFFFAOYSA-N 0.000 claims description 4
- XLBFHVSNCHNIPX-UHFFFAOYSA-N 6-[amino-(6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)N=C1 XLBFHVSNCHNIPX-UHFFFAOYSA-N 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- BZAUMUPAJAUTHA-UHFFFAOYSA-N 6-[(5-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-ethoxyphenyl)-1-methylquinolin-2-one Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3N(C)C(=O)C=2)C(O)(C=2SC(Cl)=CC=2)C=2N(C=NC=2)C)=C1 BZAUMUPAJAUTHA-UHFFFAOYSA-N 0.000 claims description 3
- BEVOPAAKIATVHN-UHFFFAOYSA-N 6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-ethoxyphenyl)-1-methylquinolin-2-one Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3N(C)C(=O)C=2)C(O)(C=2N(C=NC=2)C)C=2C=NC(Cl)=CC=2)=C1 BEVOPAAKIATVHN-UHFFFAOYSA-N 0.000 claims description 3
- 125000002346 iodo group Chemical group I* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- YOGPFYLNYXXWKY-UHFFFAOYSA-N 6-[1-benzothiophen-2-yl-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC2=CC=CC=C2S1 YOGPFYLNYXXWKY-UHFFFAOYSA-N 0.000 claims description 2
- VEUMJJHOMVERCX-UHFFFAOYSA-N 6-[amino-(3-methylimidazol-4-yl)-(6-methylpyridin-3-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one Chemical compound C1=NC(C)=CC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CN=CN1C VEUMJJHOMVERCX-UHFFFAOYSA-N 0.000 claims description 2
- STRMBPADZIUWFR-UHFFFAOYSA-N 6-[amino-(3-methylimidazol-4-yl)-pyridin-3-ylmethyl]-4-(3-chlorophenyl)-1-(cyclopropylmethyl)quinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(CC3CC3)C2=CC=1)C1=CC=CN=C1 STRMBPADZIUWFR-UHFFFAOYSA-N 0.000 claims description 2
- LBTJUJRSFIUISO-UHFFFAOYSA-N 6-[amino-(5-chloropyridin-2-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-(cyclopropylmethyl)quinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1N=CC(Cl)=CC=1)C1=CC=C(N(CC2CC2)C(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 LBTJUJRSFIUISO-UHFFFAOYSA-N 0.000 claims description 2
- MGIIKDWBCXIXAL-UHFFFAOYSA-N 6-[amino-(5-chloropyridin-2-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1N=CC(Cl)=CC=1)C1=CC=C(N(C)C(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 MGIIKDWBCXIXAL-UHFFFAOYSA-N 0.000 claims description 2
- HISLUXXUUNDPHG-UHFFFAOYSA-N 6-[amino-(5-chlorothiophen-2-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)S1 HISLUXXUUNDPHG-UHFFFAOYSA-N 0.000 claims description 2
- IXWHLDUAMCHVQX-UHFFFAOYSA-N 6-[amino-(6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methyl]-4-(3,5-dichlorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=C(Cl)C=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)N=C1 IXWHLDUAMCHVQX-UHFFFAOYSA-N 0.000 claims description 2
- XQHDYAHKRUSHDX-UHFFFAOYSA-N 6-[amino-(6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)C1=CC=C(Cl)N=C1 XQHDYAHKRUSHDX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 13
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 10
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 10
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- MXAPENZXKHWMTI-UHFFFAOYSA-N 6-[amino-(5-chlorothiophen-2-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-ethoxyphenyl)-1-methylquinolin-2-one Chemical compound NC(C=1C=C2C(=CC(N(C2=CC1)C)=O)C1=CC(=CC=C1)OCC)(C=1N(C=NC1)C)C=1SC(=CC1)Cl MXAPENZXKHWMTI-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 description 109
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
- 239000007787 solid Substances 0.000 description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 51
- 239000000543 intermediate Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- 239000000203 mixture Substances 0.000 description 30
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 230000002159 abnormal effect Effects 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 239000003112 inhibitor Substances 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- 239000012267 brine Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 239000012043 crude product Substances 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 241000124008 Mammalia Species 0.000 description 21
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 17
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- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 16
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
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- 239000000651 prodrug Substances 0.000 description 14
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 12
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- 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 description 12
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- YKPYIPVDTNNYCN-INIZCTEOSA-N prinomastat Chemical compound ONC(=O)[C@H]1C(C)(C)SCCN1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=NC=C1 YKPYIPVDTNNYCN-INIZCTEOSA-N 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
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- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
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- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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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
- C07D401/02—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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11970299P | 1999-02-11 | 1999-02-11 | |
| US60/119,702 | 1999-02-11 | ||
| PCT/IB2000/000121 WO2000047574A1 (en) | 1999-02-11 | 2000-02-04 | Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004029709A Division JP4216740B2 (ja) | 1999-02-11 | 2004-02-05 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
| JP2004211298A Division JP2005002124A (ja) | 1999-02-11 | 2004-07-20 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
Publications (2)
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| JP2002536444A JP2002536444A (ja) | 2002-10-29 |
| JP4090200B2 true JP4090200B2 (ja) | 2008-05-28 |
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| JP2000598494A Expired - Fee Related JP4090200B2 (ja) | 1999-02-11 | 2000-02-04 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
| JP2004029709A Expired - Fee Related JP4216740B2 (ja) | 1999-02-11 | 2004-02-05 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
| JP2004211298A Pending JP2005002124A (ja) | 1999-02-11 | 2004-07-20 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004029709A Expired - Fee Related JP4216740B2 (ja) | 1999-02-11 | 2004-02-05 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
| JP2004211298A Pending JP2005002124A (ja) | 1999-02-11 | 2004-07-20 | 抗癌薬として有用なヘテロアリール置換キノリン−２−オン誘導体 |
Country Status (39)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007326868A (ja) * | 2000-01-21 | 2007-12-20 | Osi Pharmaceuticals Inc | 抗癌性化合物および前記化合物を合成するのに有用なエナンチオマー分離法 |
Families Citing this family (91)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AU762423B2 (en) * | 1998-07-06 | 2003-06-26 | Janssen Pharmaceutica N.V. | Farnesyl protein transferase inhibitors with In Vivo radiosensitizing properties |
| OA11833A (en) * | 1999-02-11 | 2005-08-23 | Pfizer Prod Inc | Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents. |
| ES2216987T3 (es) | 1999-11-05 | 2004-11-01 | Cytovia, Inc. | 4h-cromeno sustituido y analogos como activadores de caspasas e industores de la apoptosis, y uso de los mismos. |
| DE60008206T2 (de) * | 1999-11-30 | 2004-12-02 | Pfizer Products Inc., Groton | Chinolinderivate verwendbar zur Hemmung der Farnesyl-Protein Transferase |
| WO2001054688A1 (en) * | 2000-01-28 | 2001-08-02 | Merck & Co., Inc. | Treatment or prevention of prostate cancer with a cox-2 selective inhibiting drug |
| JO2361B1 (en) | 2000-06-22 | 2006-12-12 | جانسين فارماسيوتيكا ان. في | Enaniumer 1,2-anylated quinoline inhibitor for the transporter - farnesyl |
| EP1170011A1 (en) * | 2000-07-06 | 2002-01-09 | Boehringer Ingelheim International GmbH | Novel use of inhibitors of the epidermal growth factor receptor |
| AU2001293826A1 (en) | 2000-09-25 | 2002-04-02 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors |
| US7173040B2 (en) | 2000-09-25 | 2007-02-06 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 6-[(substituted phenyl)methyl]-quinoline and quinazoline derinazoline derivatives |
| WO2002024687A1 (en) * | 2000-09-25 | 2002-03-28 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives |
| AU2002220559A1 (en) * | 2000-09-25 | 2002-04-02 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 6-heterocyclylmethyl quinoline and quinazoline derivatives |
| CA2421782A1 (en) * | 2000-10-02 | 2002-04-11 | Janssen Pharmaceutica N.V. | Quinoline and quinolinone derivatives as metabotropic glutamate receptor antagonists |
| ES2328225T3 (es) | 2000-11-21 | 2009-11-11 | Janssen Pharmaceutica Nv | Derivados benzoheterociclicos inhibidores de la farnesil-transferasa. |
| ATE319704T1 (de) | 2000-12-27 | 2006-03-15 | Janssen Pharmaceutica Nv | Farnesyltransferase hemmende, in der 4-stellung substituierte chinolin- und chinazolinderivate |
| US20040067968A1 (en) * | 2000-12-27 | 2004-04-08 | Angibaud Patrick Rene | Farnesyl transferase inhibiting 4-heterocyclyl quinoline and quinazoline |
| WO2002092076A1 (en) * | 2001-05-16 | 2002-11-21 | Cytovia, Inc. | Substituted coumarins and quinolines as caspases activators |
| US6858607B1 (en) | 2001-05-16 | 2005-02-22 | Cytovia, Inc. | 7,8-fused 4H-chromene and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| WO2002092594A1 (en) * | 2001-05-16 | 2002-11-21 | Cytovia, Inc. | Substituted 4h-chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| US20030139332A1 (en) * | 2001-07-09 | 2003-07-24 | The Regents Of The University Of California | Use of matrix metalloproteinase inhibitors to mitigate nerve damage |
| EP1458720B1 (en) | 2001-12-19 | 2009-03-18 | Janssen Pharmaceutica N.V. | 1,8-annelated quinoline derivatives substituted with carbon-linked triazoles as farnesyl transferase inhibitors |
| JP4450628B2 (ja) * | 2002-03-22 | 2010-04-14 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ファルネシルトランスフェラーゼインヒビターとして使用するためのベンジルイミダゾリル置換２−キノリンおよびキナゾリン誘導体 |
| PL218788B1 (pl) * | 2002-03-29 | 2015-01-30 | Janssen Pharmaceutica Nv | Znakowane radioaktywnie pochodne chinoliny i jej zastosowanie |
| WO2003087101A1 (en) | 2002-04-15 | 2003-10-23 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting tricyclic quinazoline derivatives substituted with carbon-linked imidazoles or triazoles |
| JP2005531566A (ja) | 2002-05-16 | 2005-10-20 | サイトビア インコーポレイティッド | カスパーゼ活性化剤およびアポトーシス誘導物質としての置換４−アリール−４ｈ−ピロロ［２，３−ｈ］クロメンおよび類似体ならびにそれらの使用 |
| US7476741B2 (en) | 2002-05-16 | 2009-01-13 | Cytovia, Inc. | Substituted 4H-chromens, 2H-chromenes, chromans and analogs as activators of caspases and inducers of apoptosis and the use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2007326868A (ja) * | 2000-01-21 | 2007-12-20 | Osi Pharmaceuticals Inc | 抗癌性化合物および前記化合物を合成するのに有用なエナンチオマー分離法 |
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