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
- Publication number
- 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
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- chloro
- aryl
- alkyl
- phenyl
- 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.)
- Expired - Fee Related
Links
- 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
- 230000010261 cell growth Effects 0.000 description 17
- 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
- 230000037361 pathway Effects 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 229940002612 prodrug Drugs 0.000 description 14
- 239000000651 prodrug Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 201000011510 cancer Diseases 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 102000004357 Transferases Human genes 0.000 description 10
- 108090000992 Transferases Proteins 0.000 description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000003287 optical effect Effects 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 8
- NYDUXVXIIVUYFN-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-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=CC=C(Cl)N=C1 NYDUXVXIIVUYFN-UHFFFAOYSA-N 0.000 description 8
- HPQBMSVVOVTYBL-UHFFFAOYSA-N 6-bromo-4-(3-chlorophenyl)-2-methoxyquinoline Chemical compound C=12C=C(Br)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 HPQBMSVVOVTYBL-UHFFFAOYSA-N 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 8
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- QYEMNJMSULGQRD-UHFFFAOYSA-N methyl-1H-quinolin-2-one Natural products C1=CC=C2C=CC(=O)N(C)C2=C1 QYEMNJMSULGQRD-UHFFFAOYSA-N 0.000 description 8
- 108010014186 ras Proteins Proteins 0.000 description 8
- 0 CCC([C@]1C=*C(*)=O)=NC(O*)=C(*)[C@]1C(C(C)=C)=CC Chemical compound CCC([C@]1C=*C(*)=O)=NC(O*)=C(*)[C@]1C(C(C)=C)=CC 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000701806 Human papillomavirus Species 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 6
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 102000016914 ras Proteins Human genes 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 6
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 229930185107 quinolinone Natural products 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- VVFIVMKKDHRTTO-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)C1=CC=C(Cl)N=C1 VVFIVMKKDHRTTO-UHFFFAOYSA-N 0.000 description 4
- FOJLVQCNFVMAHF-UHFFFAOYSA-N 6-bromo-2-methoxy-4-(3-methoxyphenyl)quinoline Chemical compound COC1=CC=CC(C=2C3=CC(Br)=CC=C3N=C(OC)C=2)=C1 FOJLVQCNFVMAHF-UHFFFAOYSA-N 0.000 description 4
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 101000643890 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 5 Proteins 0.000 description 4
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 4
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 4
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 4
- 108700020796 Oncogene Proteins 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 102100021017 Ubiquitin carboxyl-terminal hydrolase 5 Human genes 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 239000004037 angiogenesis inhibitor Substances 0.000 description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 230000006126 farnesylation Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000002821 scintillation proximity assay Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 239000002525 vasculotropin inhibitor Substances 0.000 description 4
- IAKVMGVCRCVJOM-UHFFFAOYSA-N (5-chlorothiophen-2-yl)-(3-methylimidazol-4-yl)methanone Chemical compound CN1C=NC=C1C(=O)C1=CC=C(Cl)S1 IAKVMGVCRCVJOM-UHFFFAOYSA-N 0.000 description 3
- LECYMYDOCFNNCH-UHFFFAOYSA-N 1-methyl-3-propylquinolin-2-one Chemical compound C(CC)C=1C(N(C2=CC=CC=C2C1)C)=O LECYMYDOCFNNCH-UHFFFAOYSA-N 0.000 description 3
- YJYDOBIWVPJVBK-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(5-chloropyridin-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1-(cyclopropylmethyl)quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1N=CC(Cl)=CC=1)C1=CC=C(N(CC2CC2)C(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 YJYDOBIWVPJVBK-UHFFFAOYSA-N 0.000 description 3
- RELQZZQIJBNBEJ-UHFFFAOYSA-N 6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-ethoxyphenyl)-1h-quinolin-2-one Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3NC(=O)C=2)C(O)(C=2N(C=NC=2)C)C=2C=NC(Cl)=CC=2)=C1 RELQZZQIJBNBEJ-UHFFFAOYSA-N 0.000 description 3
- YJYXNTFLPZFNFM-UHFFFAOYSA-N 6-bromo-4-(3-ethoxyphenyl)-2-methoxyquinoline Chemical compound CCOC1=CC=CC(C=2C3=CC(Br)=CC=C3N=C(OC)C=2)=C1 YJYXNTFLPZFNFM-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010000830 Acute leukaemia Diseases 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 208000023514 Barrett esophagus Diseases 0.000 description 3
- 208000023665 Barrett oesophagus Diseases 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 3
- 206010005949 Bone cancer Diseases 0.000 description 3
- 208000018084 Bone neoplasm Diseases 0.000 description 3
- 206010006143 Brain stem glioma Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 3
- 206010014733 Endometrial cancer Diseases 0.000 description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 3
- 201000001342 Fallopian tube cancer Diseases 0.000 description 3
- 208000013452 Fallopian tube neoplasm Diseases 0.000 description 3
- 208000009849 Female Genital Neoplasms Diseases 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 208000017604 Hodgkin disease Diseases 0.000 description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 3
- 206010052178 Lymphocytic lymphoma Diseases 0.000 description 3
- 208000032271 Malignant tumor of penis Diseases 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 3
- 206010061336 Pelvic neoplasm Diseases 0.000 description 3
- 208000002471 Penile Neoplasms Diseases 0.000 description 3
- 206010034299 Penile cancer Diseases 0.000 description 3
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 3
- 201000005746 Pituitary adenoma Diseases 0.000 description 3
- 206010061538 Pituitary tumour benign Diseases 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- 208000000453 Skin Neoplasms Diseases 0.000 description 3
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 description 3
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 3
- 206010046392 Ureteric cancer Diseases 0.000 description 3
- 206010046431 Urethral cancer Diseases 0.000 description 3
- 206010046458 Urethral neoplasms Diseases 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 description 3
- 206010047741 Vulval cancer Diseases 0.000 description 3
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 201000005188 adrenal gland cancer Diseases 0.000 description 3
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 208000025997 central nervous system neoplasm Diseases 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 208000024207 chronic leukemia Diseases 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 201000004101 esophageal cancer Diseases 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 201000010536 head and neck cancer Diseases 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 208000029559 malignant endocrine neoplasm Diseases 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 3
- 230000001613 neoplastic effect Effects 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 230000000849 parathyroid Effects 0.000 description 3
- 208000021310 pituitary gland adenoma Diseases 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 206010038038 rectal cancer Diseases 0.000 description 3
- 201000001275 rectum cancer Diseases 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 201000002314 small intestine cancer Diseases 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 206010062261 spinal cord neoplasm Diseases 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 201000002510 thyroid cancer Diseases 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- 238000000844 transformation Methods 0.000 description 3
- 201000005112 urinary bladder cancer Diseases 0.000 description 3
- 206010046766 uterine cancer Diseases 0.000 description 3
- 208000037965 uterine sarcoma Diseases 0.000 description 3
- 206010046885 vaginal cancer Diseases 0.000 description 3
- 208000013139 vaginal neoplasm Diseases 0.000 description 3
- 201000005102 vulva cancer Diseases 0.000 description 3
- HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 2
- QPLJYAKLSCXZSF-UHFFFAOYSA-N 2,2,2-trichloroethyl carbamate Chemical compound NC(=O)OCC(Cl)(Cl)Cl QPLJYAKLSCXZSF-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- YTYIXYJZDORRCN-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(5-chloropyridin-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1N=CC(Cl)=CC=1)C1=CC=C(NC(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 YTYIXYJZDORRCN-UHFFFAOYSA-N 0.000 description 2
- GQEOZGPDJJPQQW-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(5-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-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=CC=C(Cl)S1 GQEOZGPDJJPQQW-UHFFFAOYSA-N 0.000 description 2
- YKYIKOIWKLEMIT-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(6-chloropyridin-3-yl)-[(4-methoxyphenyl)methylamino]-(3-methylimidazol-4-yl)methyl]-1-(cyclopropylmethyl)quinolin-2-one Chemical compound C1=CC(OC)=CC=C1CNC(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(CC3CC3)C2=CC=1)(C=1C=NC(Cl)=CC=1)C1=CN=CN1C YKYIKOIWKLEMIT-UHFFFAOYSA-N 0.000 description 2
- ZVRAOXWHDATMDN-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(6-chloropyridin-3-yl)-[(4-methoxyphenyl)methylideneamino]-(3-methylimidazol-4-yl)methyl]-1-(cyclopropylmethyl)quinolin-2-one Chemical compound C1=CC(OC)=CC=C1C=NC(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(CC3CC3)C2=CC=1)(C=1C=NC(Cl)=CC=1)C1=CN=CN1C ZVRAOXWHDATMDN-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 2
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 2
- 241001227713 Chiron Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061252 Intraocular melanoma Diseases 0.000 description 2
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 2
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 2
- 229940121849 Mitotic inhibitor Drugs 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 201000005969 Uveal melanoma Diseases 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000002280 anti-androgenic effect Effects 0.000 description 2
- 230000003388 anti-hormonal effect Effects 0.000 description 2
- 239000000051 antiandrogen Substances 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 230000030944 contact inhibition Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 208000030381 cutaneous melanoma Diseases 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- AQLPDLOXKZRZEV-UHFFFAOYSA-N dipyridin-3-ylmethanone Chemical compound C=1C=CN=CC=1C(=O)C1=CC=CN=C1 AQLPDLOXKZRZEV-UHFFFAOYSA-N 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 229940121647 egfr inhibitor Drugs 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000003966 growth inhibitor Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 230000003463 hyperproliferative effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 201000002575 ocular melanoma Diseases 0.000 description 2
- 150000002902 organometallic compounds Chemical class 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 235000015927 pasta Nutrition 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Chemical class 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 201000003708 skin melanoma Diseases 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 201000011294 ureter cancer Diseases 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- WYNOYTAQXHTBAN-UHFFFAOYSA-N (2-amino-5-bromophenyl)-(3,5-dichlorophenyl)methanone Chemical compound NC1=CC=C(Br)C=C1C(=O)C1=CC(Cl)=CC(Cl)=C1 WYNOYTAQXHTBAN-UHFFFAOYSA-N 0.000 description 1
- LTVIJEFEZVFIST-AZUAARDMSA-N (2r,3r)-1-[4-[(2-chloro-4-fluorophenyl)methoxy]phenyl]sulfonyl-n,3-dihydroxy-3-methylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@](C)(O)CCCN1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=C(F)C=C1Cl LTVIJEFEZVFIST-AZUAARDMSA-N 0.000 description 1
- ZHCXOELPVFPGHI-PZJWPPBQSA-N (2r,3r)-1-[4-[(4-fluoro-2-methylphenyl)methoxy]phenyl]sulfonyl-n,3-dihydroxy-3-methylpiperidine-2-carboxamide Chemical compound CC1=CC(F)=CC=C1COC1=CC=C(S(=O)(=O)N2[C@H]([C@](C)(O)CCC2)C(=O)NO)C=C1 ZHCXOELPVFPGHI-PZJWPPBQSA-N 0.000 description 1
- ZFYHDXZZLIRENX-UHFFFAOYSA-N (3-methylimidazol-4-yl)-(6-methylpyridin-3-yl)methanone Chemical compound C1=NC(C)=CC=C1C(=O)C1=CN=CN1C ZFYHDXZZLIRENX-UHFFFAOYSA-N 0.000 description 1
- KENXCMUVEIUJKP-UHFFFAOYSA-N (3-methylimidazol-4-yl)-thiophen-2-ylmethanone Chemical compound CN1C=NC=C1C(=O)C1=CC=CS1 KENXCMUVEIUJKP-UHFFFAOYSA-N 0.000 description 1
- YZIGEYGKVJNXSU-QGZVFWFLSA-N (3r)-3-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxolane-3-carboxamide Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N[C@]1(C(=O)NO)CCOC1 YZIGEYGKVJNXSU-QGZVFWFLSA-N 0.000 description 1
- XCCOVBJHUQPLKI-UHFFFAOYSA-N (5-chloropyridin-2-yl)-(3-methylimidazol-4-yl)methanone Chemical compound CN1C=NC=C1C(=O)C1=CC=C(Cl)C=N1 XCCOVBJHUQPLKI-UHFFFAOYSA-N 0.000 description 1
- ICOQHUYCICFZCT-UHFFFAOYSA-N (5-chlorothiophen-2-yl)-[2-methoxy-4-(3-methoxyphenyl)quinolin-6-yl]-(3-methylimidazol-4-yl)methanol Chemical compound COC1=CC=CC(C=2C3=CC(=CC=C3N=C(OC)C=2)C(O)(C=2SC(Cl)=CC=2)C=2N(C=NC=2)C)=C1 ICOQHUYCICFZCT-UHFFFAOYSA-N 0.000 description 1
- KEYWYPCZOIYOMW-UHFFFAOYSA-N (5-chlorothiophen-2-yl)-[4-(3-ethoxyphenyl)-2-methoxyquinolin-6-yl]-(3-methylimidazol-4-yl)methanol Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3N=C(OC)C=2)C(O)(C=2SC(Cl)=CC=2)C=2N(C=NC=2)C)=C1 KEYWYPCZOIYOMW-UHFFFAOYSA-N 0.000 description 1
- WRORTJWDTINQCP-UHFFFAOYSA-N (6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methanone Chemical compound CN1C=NC=C1C(=O)C1=CC=C(Cl)N=C1 WRORTJWDTINQCP-UHFFFAOYSA-N 0.000 description 1
- HPAPOIQFTHCIBQ-UHFFFAOYSA-N (6-chloropyridin-3-yl)-[4-(3,5-dichlorophenyl)-2-methoxyquinolin-6-yl]-(3-methylimidazol-4-yl)methanol Chemical compound C=12C=C(C(O)(C=3N(C=NC=3)C)C=3C=NC(Cl)=CC=3)C=CC2=NC(OC)=CC=1C1=CC(Cl)=CC(Cl)=C1 HPAPOIQFTHCIBQ-UHFFFAOYSA-N 0.000 description 1
- KMPLYESDOZJASB-PAHRJMAXSA-N (6s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-hydroxy-6-methoxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one;(z)-n-carbamoyl-2-ethylbut-2-enamide;6-ethoxy-1,3-benzothiazole-2-sulfonamide Chemical compound CC\C(=C\C)C(=O)NC(N)=O.CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1.C([C@@]12C)CC(=O)C=C1[C@@H](OC)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 KMPLYESDOZJASB-PAHRJMAXSA-N 0.000 description 1
- HCUOEKSZWPGJIM-YBRHCDHNSA-N (e,2e)-2-hydroxyimino-6-methoxy-4-methyl-5-nitrohex-3-enamide Chemical compound COCC([N+]([O-])=O)\C(C)=C\C(=N/O)\C(N)=O HCUOEKSZWPGJIM-YBRHCDHNSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 125000005943 1,2,3,6-tetrahydropyridyl group Chemical group 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
- HBLYFJJSXFBDFY-UHFFFAOYSA-N 1-(cyclopropylmethyl)quinolin-2-one Chemical compound O=C1C=CC2=CC=CC=C2N1CC1CC1 HBLYFJJSXFBDFY-UHFFFAOYSA-N 0.000 description 1
- NSEFYIMLDOSGRT-UHFFFAOYSA-N 1-benzothiophen-2-yl-[4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(3-methylimidazol-4-yl)methanol Chemical compound C=12C=C(C(O)(C=3SC4=CC=CC=C4C=3)C=3N(C=NC=3)C)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 NSEFYIMLDOSGRT-UHFFFAOYSA-N 0.000 description 1
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 150000004327 2-hydroxyquinolines Chemical class 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
- NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 1
- NMDUJEUWNLCXSB-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[1-(hydroxyamino)-2-methyl-1-oxopropan-2-yl]amino]propanoic acid Chemical compound C1=CC(S(=O)(=O)N(CCC(O)=O)C(C)(C)C(=O)NO)=CC=C1OC1=CC=C(F)C=C1 NMDUJEUWNLCXSB-UHFFFAOYSA-N 0.000 description 1
- PDCBVHDMAFCHPK-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[1-(hydroxycarbamoyl)cyclobutyl]amino]propanoic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCC1 PDCBVHDMAFCHPK-UHFFFAOYSA-N 0.000 description 1
- WARXYAHFCARUNH-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[4-(hydroxycarbamoyl)oxan-4-yl]amino]propanoic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCOCC1 WARXYAHFCARUNH-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
- AVGQUILLCRPWKH-UHFFFAOYSA-N 4-(1h-imidazol-5-yl)-3-methyl-1h-quinolin-2-one Chemical class C12=CC=CC=C2NC(=O)C(C)=C1C1=CN=CN1 AVGQUILLCRPWKH-UHFFFAOYSA-N 0.000 description 1
- PJVIOQSNONDRNZ-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(3-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-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=C(Cl)C=CS1 PJVIOQSNONDRNZ-UHFFFAOYSA-N 0.000 description 1
- DPJSRSKCUVHAIU-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(3-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)C1=C(Cl)C=CS1 DPJSRSKCUVHAIU-UHFFFAOYSA-N 0.000 description 1
- YCORMMYSDQVERB-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(5-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)C1=CC=C(Cl)S1 YCORMMYSDQVERB-UHFFFAOYSA-N 0.000 description 1
- FJMKMEUBCQSMIU-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(5-chlorothiophen-2-yl)-hydroxymethyl]-1-methylquinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(C(O)C=3SC(Cl)=CC=3)C=C2C=1C1=CC=CC(Cl)=C1 FJMKMEUBCQSMIU-UHFFFAOYSA-N 0.000 description 1
- QUIQGEBRVBJNJC-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(6-chloropyridin-3-yl)-[(4-methoxyphenyl)methylamino]-(3-methylimidazol-4-yl)methyl]-1h-quinolin-2-one Chemical compound C1=CC(OC)=CC=C1CNC(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)(C=1C=NC(Cl)=CC=1)C1=CN=CN1C QUIQGEBRVBJNJC-UHFFFAOYSA-N 0.000 description 1
- LWSHCFSKJXZSHG-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[hydroxy(dipyridin-3-yl)methyl]-1h-quinolin-2-one Chemical compound C=1C=CN=CC=1C(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)(O)C1=CC=CN=C1 LWSHCFSKJXZSHG-UHFFFAOYSA-N 0.000 description 1
- QDUGXJLFXYAAEA-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[hydroxy-(3-methylimidazol-4-yl)-quinolin-3-ylmethyl]-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C=CC=CC2=NC=1)C1=CC=C(N(C)C(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 QDUGXJLFXYAAEA-UHFFFAOYSA-N 0.000 description 1
- GXGNMSUZZFXSPX-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[hydroxy-(3-methylimidazol-4-yl)-quinolin-3-ylmethyl]-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C=CC=CC2=NC=1)C1=CC=C(NC(=O)C=C2C=3C=C(Cl)C=CC=3)C2=C1 GXGNMSUZZFXSPX-UHFFFAOYSA-N 0.000 description 1
- CTPCQZYNPMMKOQ-UHFFFAOYSA-N 4-(3-ethoxyphenyl)-6-[hydroxy(dipyridin-3-yl)methyl]-1h-quinolin-2-one Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3NC(=O)C=2)C(O)(C=2C=NC=CC=2)C=2C=NC=CC=2)=C1 CTPCQZYNPMMKOQ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CYZMUIMLRBJSRO-UHFFFAOYSA-N 4-[[4-(4-chlorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-4-carboxamide Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1S(=O)(=O)NC1(C(=O)NO)CCOCC1 CYZMUIMLRBJSRO-UHFFFAOYSA-N 0.000 description 1
- ZBRHTUMWSDPCMI-UHFFFAOYSA-N 4-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-4-carboxamide Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)NC1(C(=O)NO)CCOCC1 ZBRHTUMWSDPCMI-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- FIPUXZHLOWSMIV-UHFFFAOYSA-N 5-chloro-n-methoxy-n-methylthiophene-2-carboxamide Chemical compound CON(C)C(=O)C1=CC=C(Cl)S1 FIPUXZHLOWSMIV-UHFFFAOYSA-N 0.000 description 1
- VBJYLSVRDQEMLX-UHFFFAOYSA-N 6-[(5-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-ethoxyphenyl)-1h-quinolin-2-one Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3NC(=O)C=2)C(O)(C=2SC(Cl)=CC=2)C=2N(C=NC=2)C)=C1 VBJYLSVRDQEMLX-UHFFFAOYSA-N 0.000 description 1
- DZASCOOFUFOKRZ-UHFFFAOYSA-N 6-[(5-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-methoxyphenyl)-1-methylquinolin-2-one Chemical compound COC1=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 DZASCOOFUFOKRZ-UHFFFAOYSA-N 0.000 description 1
- OAYOUVGBNBHKTD-UHFFFAOYSA-N 6-[(5-chlorothiophen-2-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-methoxyphenyl)-1h-quinolin-2-one Chemical compound COC1=CC=CC(C=2C3=CC(=CC=C3NC(=O)C=2)C(O)(C=2SC(Cl)=CC=2)C=2N(C=NC=2)C)=C1 OAYOUVGBNBHKTD-UHFFFAOYSA-N 0.000 description 1
- XQWNNXWQSWCOOB-UHFFFAOYSA-N 6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3,5-dichlorophenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(O)(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 XQWNNXWQSWCOOB-UHFFFAOYSA-N 0.000 description 1
- HXAOHRAUKJUHNH-UHFFFAOYSA-N 6-[(6-chloropyridin-3-yl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3,5-dichlorophenyl)-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=C(Cl)C=3)=CC(=O)NC2=CC=1)C1=CC=C(Cl)N=C1 HXAOHRAUKJUHNH-UHFFFAOYSA-N 0.000 description 1
- CMCMQSVHBYWGIW-UHFFFAOYSA-N 6-[1-benzothiophen-2-yl-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1h-quinolin-2-one Chemical compound CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)NC2=CC=1)C1=CC2=CC=CC=C2S1 CMCMQSVHBYWGIW-UHFFFAOYSA-N 0.000 description 1
- BWJWOOLJUFMWHW-UHFFFAOYSA-N 6-[amino-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-ethynylphenyl)-1-methylquinolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(C=CC=3)C#C)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 BWJWOOLJUFMWHW-UHFFFAOYSA-N 0.000 description 1
- PTTQSWFSBPLTFS-UHFFFAOYSA-N 6-bromo-2-methoxy-4-(3-propan-2-yloxyphenyl)quinoline Chemical compound C=12C=C(Br)C=CC2=NC(OC)=CC=1C1=CC=CC(OC(C)C)=C1 PTTQSWFSBPLTFS-UHFFFAOYSA-N 0.000 description 1
- IOUFOFJNLWSTPM-UHFFFAOYSA-N 6-bromo-4-(3,5-dichlorophenyl)-1h-quinolin-2-one Chemical compound ClC1=CC(Cl)=CC(C=2C3=CC(Br)=CC=C3NC(=O)C=2)=C1 IOUFOFJNLWSTPM-UHFFFAOYSA-N 0.000 description 1
- HWBOMRLSOHZEMX-UHFFFAOYSA-N 6-bromo-4-(3,5-dichlorophenyl)-2-methoxyquinoline Chemical compound C=12C=C(Br)C=CC2=NC(OC)=CC=1C1=CC(Cl)=CC(Cl)=C1 HWBOMRLSOHZEMX-UHFFFAOYSA-N 0.000 description 1
- OAOZBPIEAJAHEO-UHFFFAOYSA-N 6-bromo-4-(3-ethoxyphenyl)-1h-quinolin-2-one Chemical compound CCOC1=CC=CC(C=2C3=CC(Br)=CC=C3NC(=O)C=2)=C1 OAOZBPIEAJAHEO-UHFFFAOYSA-N 0.000 description 1
- AULWPXHFRBLPAE-UHFFFAOYSA-N 6-chloropyridine Chemical compound ClC1=C=CC=C[N]1 AULWPXHFRBLPAE-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- XQURALONCHHJEK-DJNXLDHESA-N C1COC[C@@H](C1C(=O)NO)NS(=O)(=O)C2=CC=C(C=C2)OC3=CC=C(C=C3)Cl Chemical compound C1COC[C@@H](C1C(=O)NO)NS(=O)(=O)C2=CC=C(C=C2)OC3=CC=C(C=C3)Cl XQURALONCHHJEK-DJNXLDHESA-N 0.000 description 1
- GXJWWOSOULOLRQ-UHFFFAOYSA-N CCOC1=CC=CC(=C1)C2=CC(=NC3=C2CC(C=C3)(C(C4=CSC=C4)(C5=CN=CN5C)O)Cl)OC Chemical compound CCOC1=CC=CC(=C1)C2=CC(=NC3=C2CC(C=C3)(C(C4=CSC=C4)(C5=CN=CN5C)O)Cl)OC GXJWWOSOULOLRQ-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- 241000694440 Colpidium aqueous Species 0.000 description 1
- VHHGUBHZBLPTKL-UHFFFAOYSA-N Cp-471358 Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCCC1 VHHGUBHZBLPTKL-UHFFFAOYSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 102000007317 Farnesyltranstransferase Human genes 0.000 description 1
- 108010007508 Farnesyltranstransferase Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 102100030417 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- FTFRZXFNZVCRSK-UHFFFAOYSA-N N4-(3-chloro-4-fluorophenyl)-N6-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FTFRZXFNZVCRSK-UHFFFAOYSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- 230000006179 O-acylation Effects 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- ZJPGOXWRFNKIQL-JYJNAYRXSA-N Phe-Pro-Pro Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=CC=C1 ZJPGOXWRFNKIQL-JYJNAYRXSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 101710108792 Stromelysin-2 Proteins 0.000 description 1
- 102100028847 Stromelysin-3 Human genes 0.000 description 1
- 108050005271 Stromelysin-3 Proteins 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- OKWSKXBZPHOTCS-UHFFFAOYSA-N [4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(3-chlorothiophen-2-yl)-(3-methylimidazol-4-yl)methanol Chemical compound C=12C=C(C(O)(C=3N(C=NC=3)C)C3=C(C=CS3)Cl)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 OKWSKXBZPHOTCS-UHFFFAOYSA-N 0.000 description 1
- CPGBSMLMEQVTEY-UHFFFAOYSA-N [4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(3-methylimidazol-4-yl)-(6-methylpyridin-3-yl)methanol Chemical compound C=12C=C(C(O)(C=3N(C=NC=3)C)C=3C=NC(C)=CC=3)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 CPGBSMLMEQVTEY-UHFFFAOYSA-N 0.000 description 1
- GAROJBOUUQZBCN-UHFFFAOYSA-N [4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(5-chlorothiophen-2-yl)-(3-methylimidazol-4-yl)methanol Chemical compound C=12C=C(C(O)(C=3SC(Cl)=CC=3)C=3N(C=NC=3)C)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 GAROJBOUUQZBCN-UHFFFAOYSA-N 0.000 description 1
- PSQLVKMNZPHFRL-UHFFFAOYSA-N [4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(5-chlorothiophen-2-yl)methanone Chemical compound C=12C=C(C(=O)C=3SC(Cl)=CC=3)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 PSQLVKMNZPHFRL-UHFFFAOYSA-N 0.000 description 1
- JGCJPQBMCVEYMO-UHFFFAOYSA-N [4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-(6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methanol Chemical compound C=12C=C(C(O)(C=3N(C=NC=3)C)C=3C=NC(Cl)=CC=3)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 JGCJPQBMCVEYMO-UHFFFAOYSA-N 0.000 description 1
- YYRFJWLWPFPLGA-UHFFFAOYSA-N [4-(3-chlorophenyl)-2-methoxyquinolin-6-yl]-dipyridin-3-ylmethanol Chemical compound C=12C=C(C(O)(C=3C=NC=CC=3)C=3C=NC=CC=3)C=CC2=NC(OC)=CC=1C1=CC=CC(Cl)=C1 YYRFJWLWPFPLGA-UHFFFAOYSA-N 0.000 description 1
- KUZIEGJTDJXBMM-UHFFFAOYSA-N [4-(3-ethoxyphenyl)-2-methoxyquinolin-6-yl]-dipyridin-3-ylmethanol Chemical compound CCOC1=CC=CC(C=2C3=CC(=CC=C3N=C(OC)C=2)C(O)(C=2C=NC=CC=2)C=2C=NC=CC=2)=C1 KUZIEGJTDJXBMM-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000004202 carbamide Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical class 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- RCKMWOKWVGPNJF-UHFFFAOYSA-N diethylcarbamazine Chemical compound CCN(CC)C(=O)N1CCN(C)CC1 RCKMWOKWVGPNJF-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 238000009099 neoadjuvant therapy Methods 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000002923 oximes Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229950003608 prinomastat Drugs 0.000 description 1
- 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
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 108700042226 ras Genes Proteins 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 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
- 229960000371 rofecoxib Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 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
- 238000009097 single-agent therapy Methods 0.000 description 1
- 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
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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)
| Publication Number | Publication Date |
|---|---|
| JP2002536444A JP2002536444A (ja) | 2002-10-29 |
| JP4090200B2 true JP4090200B2 (ja) | 2008-05-28 |
Family
ID=22385869
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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 |
|---|---|---|---|---|
| ID26987A (id) * | 1998-07-06 | 2001-02-22 | Janssen Pharmaceutica Nv | Inhibitor-inhibitor transferase protein farnesil dengan sifat-sifat peka terhadap sinar radiasi in vivo |
| TR200201296T2 (tr) * | 1999-02-11 | 2002-07-22 | Pfizer Products Inc. | Antikanser maddeleri olarak faydalı heteroaril-ikame edilmiş kinolin-2-on türevleri |
| AU781986B2 (en) * | 1999-11-05 | 2005-06-23 | Cytovia, Inc. | Substituted 4H-chromene and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| ES2212971T3 (es) * | 1999-11-30 | 2004-08-16 | Pfizer Products Inc. | Derivados de quinolina utiles para la inhibicion de la farnesil protein transferasa. |
| EP1253921A4 (en) * | 2000-01-28 | 2004-10-13 | Merck & Co Inc | TREATMENT AND PROPHYLAXIS OF PROSTATE CANCER WITH COX-2 SELECTIVE INHIBITORS |
| 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 |
| JP4974439B2 (ja) * | 2000-09-25 | 2012-07-11 | 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を阻害する６−ヘテロシクリルメチルキノリノン誘導体 |
| ATE409189T1 (de) * | 2000-09-25 | 2008-10-15 | Janssen Pharmaceutica Nv | Farnesyl transferase-hemmende 6- heterocyclylmethyl-chinolin und chinazol-derivate |
| US7053105B2 (en) | 2000-09-25 | 2006-05-30 | Janssen Pharmaceutica, N.V. | Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors |
| WO2002024683A1 (en) | 2000-09-25 | 2002-03-28 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 6-[(substituted phenyl)methyl]-quinoline and quinazoline derivatives |
| CN1703403A (zh) * | 2000-10-02 | 2005-11-30 | 詹森药业有限公司 | 趋代谢的谷氨酸盐受体拮抗剂 |
| ES2328225T3 (es) | 2000-11-21 | 2009-11-11 | Janssen Pharmaceutica Nv | Derivados benzoheterociclicos inhibidores de la farnesil-transferasa. |
| EP1351954B1 (en) * | 2000-12-27 | 2006-05-03 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting 4-heterocyclyl-quinoline and quinazoline derivatives |
| ATE319704T1 (de) | 2000-12-27 | 2006-03-15 | Janssen Pharmaceutica Nv | Farnesyltransferase hemmende, in der 4-stellung substituierte chinolin- und chinazolinderivate |
| 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 |
| EP1392283A4 (en) | 2001-05-16 | 2004-10-20 | Cytovia Inc | SUBSTITUTED CUMARINE AND CHINOLINE AS CASPASE ACTIVATORS |
| EP1392683B1 (en) * | 2001-05-16 | 2009-12-02 | Cytovia, Inc. | Substituted 4h-chromenes and analogs as activators of caspases and inducers of apoptosis and their use as anticancer agents |
| WO2003006006A1 (en) * | 2001-07-09 | 2003-01-23 | The Regents Of The University Of California | Use of matrix metalloproteinase inhibitors to mitigate nerve damage |
| CA2469275C (en) | 2001-12-19 | 2011-09-06 | Janssen Pharmaceutica N.V. | 1,8-annelated quinoline derivatives substituted with carbon-linked triazoles as farnesyl transferase inhibitors |
| ES2287466T3 (es) | 2002-03-22 | 2007-12-16 | Janssen Pharmaceutica N.V. | Derivados de 2-quinolinona y quinazolina de bencilimidazolil sustituidas como inhibidores de la farnesil transferasa. |
| NZ535438A (en) * | 2002-03-29 | 2006-08-31 | Janssen Pharmaceutica Nv | Radiolabelled quinoline and quinolinone derivatives and their use as metabotropic glutamate receptor ligands |
| CA2481480C (en) | 2002-04-15 | 2011-04-12 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting tricyclic quinazoline derivatives substituted with carbon-linked imidazoles or triazoles |
| 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 |
| CN100349887C (zh) | 2002-05-16 | 2007-11-21 | 西托维亚公司 | 取代的4－芳基－4h－吡咯并[2,3－h]色烯和类似物及其药物组合物和用途 |
| US20040186160A1 (en) * | 2002-12-13 | 2004-09-23 | Sugen, Inc. | Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors |
| AU2003286321A1 (en) * | 2002-12-19 | 2004-07-14 | Pfizer Inc. | 2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophtalmic diseases |
| PT2476667E (pt) | 2003-02-26 | 2014-09-18 | Sugen Inc | Compostos de aminoheteroarilo como inibidores da proteína quinase |
| WO2004076446A1 (ja) * | 2003-02-27 | 2004-09-10 | Chugai Seiyaku Kabushiki Kaisha | ベンゾチオフェン誘導体 |
| CA2533626A1 (en) * | 2003-07-22 | 2005-02-03 | Janssen Pharmaceutica, N.V. | Quinolinone derivatives as inhibitors of c-fms kinase |
| JP4691041B2 (ja) | 2003-11-20 | 2011-06-01 | チルドレンズ ホスピタル メディカル センター | Ｇｔｐアーゼ阻害剤および使用方法 |
| CA2559221A1 (en) * | 2004-03-18 | 2005-09-29 | Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| US20050288298A1 (en) * | 2004-03-18 | 2005-12-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| WO2005089515A2 (en) * | 2004-03-18 | 2005-09-29 | The Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| CA2559285A1 (en) * | 2004-03-18 | 2005-09-29 | Brigham And Women's Hospital, Inc. | Methods for the treatment of synucleinopathies |
| US20070293539A1 (en) * | 2004-03-18 | 2007-12-20 | Lansbury Peter T | Methods for the treatment of synucleinopathies |
| BRPI0509580A (pt) * | 2004-03-30 | 2007-11-27 | Pfizer Prod Inc | combinações de inibidores de transdução de sinal |
| JP4242911B2 (ja) | 2004-08-26 | 2009-03-25 | ファイザー・インク | プロテインキナーゼ阻害薬としてのエナンチオピュアなアミノヘテロアリール化合物 |
| EP1786777A1 (en) * | 2004-08-26 | 2007-05-23 | Pfizer, Inc. | Aminoheteroaryl compounds as protein tyrosine kinase inhibitors |
| CA2577937C (en) * | 2004-08-26 | 2010-12-21 | Pfizer Inc. | Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors |
| WO2006041900A2 (en) * | 2004-10-07 | 2006-04-20 | Cytovia, Inc. | SUBSTITUTED N-ARYL-1H-PYRAZOLO[3,4-b]QUINOLIN-4-AMINES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS |
| WO2007016539A2 (en) | 2005-07-29 | 2007-02-08 | Children's Hospital Medical Center | Gtpase inhibitors and methods of use and crystal structure of rac-1 gtpase |
| SI2447283T1 (sl) | 2005-09-07 | 2015-12-31 | Amgen Fremont Inc. | Človeška monoklonska protitelesa proti aktivin receptorski kinazi-1 (ALK-1) |
| AU2006292278B2 (en) | 2005-09-20 | 2012-03-08 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AU2006331542A1 (en) | 2005-12-23 | 2007-07-05 | Link Medicine Corporation | Treatment of synucleinopathies |
| TW200812615A (en) | 2006-03-22 | 2008-03-16 | Hoffmann La Roche | Tumor therapy with an antibody for vascular endothelial growth factor and an antibody for human epithelial growth factor receptor type 2 |
| EA200802058A1 (ru) | 2006-05-09 | 2009-06-30 | Пфайзер Продактс Инк. | Производные циклоалкиламинокислот и их фармацевтические композиции |
| AU2007287794B2 (en) | 2006-08-21 | 2013-03-28 | F. Hoffmann-La Roche Ag | Tumor therapy with an anti-VEGF antibody |
| RU2472788C9 (ru) * | 2007-05-23 | 2013-04-20 | Аллерган, Инк. | (бициклогетероарил)имидазолил)метилгетероарильные соединения как агонисты адренергических рецепторов |
| PL2155733T3 (pl) * | 2007-05-23 | 2013-02-28 | Allergan Inc | Cykliczne laktamy do leczenia jaskry lub podwyższonego ciśnienia śródgałkowego |
| US8129356B2 (en) * | 2007-10-01 | 2012-03-06 | Vanderbilt University | Bmx mediated signal transduction in irradiated vascular endothelium |
| WO2009151683A2 (en) * | 2008-03-12 | 2009-12-17 | Link Medicine Corporation | Quinolinone farnesyl transferase inhibitors for the treatment of synucleinopathies and other indications |
| DE102008022221A1 (de) * | 2008-05-06 | 2009-11-12 | Universität des Saarlandes | Inhibitoren der humanen Aldosteronsynthase CYP11B2 |
| AU2009313927A1 (en) * | 2008-11-13 | 2010-05-20 | Astrazeneca Ab | Azaquinolinone derivatives and uses thereof |
| US20100331363A1 (en) * | 2008-11-13 | 2010-12-30 | Link Medicine Corporation | Treatment of mitochondrial disorders using a farnesyl transferase inhibitor |
| US20110060005A1 (en) * | 2008-11-13 | 2011-03-10 | Link Medicine Corporation | Treatment of mitochondrial disorders using a farnesyl transferase inhibitor |
| SG172857A1 (en) * | 2009-02-09 | 2011-08-29 | Supergen Inc | Pyrrolopyrimidinyl axl kinase inhibitors |
| US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| US8642834B2 (en) | 2009-02-27 | 2014-02-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| WO2010098866A1 (en) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| AU2011223655A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AU2011223643A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2012116040A1 (en) | 2011-02-22 | 2012-08-30 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| JP2014519813A (ja) | 2011-04-25 | 2014-08-21 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 癌薬剤発見、診断、および治療におけるｅｍｔ遺伝子シグネチャーの使用 |
| DK2734205T3 (en) | 2011-07-21 | 2018-06-14 | Tolero Pharmaceuticals Inc | Heterocyclic Protein Kinase Inhibitors |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US9980942B2 (en) | 2012-05-02 | 2018-05-29 | Children's Hospital Medical Center | Rejuvenation of precursor cells |
| MY189505A (en) | 2012-10-16 | 2022-02-16 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of roryt |
| WO2014062655A1 (en) | 2012-10-16 | 2014-04-24 | Janssen Pharmaceutica Nv | HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt |
| HK1213887A1 (zh) | 2012-10-16 | 2016-07-15 | Janssen Pharmaceutica N.V. | RORγt的苯基连接的喹啉基调节剂 |
| US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
| AR094403A1 (es) | 2013-01-11 | 2015-07-29 | Hoffmann La Roche | Terapia de combinación de anticuerpos anti-her3 |
| PT2970205T (pt) | 2013-03-14 | 2019-08-26 | Tolero Pharmaceuticals Inc | Inibidores da jak2 e da alk2 e métodos para a sua utilização |
| US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
| US9284308B2 (en) | 2013-10-15 | 2016-03-15 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of RORγt |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| CA2926339A1 (en) | 2013-10-15 | 2015-04-23 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of roryt |
| CA2927182A1 (en) | 2013-10-15 | 2015-04-23 | Janssen Pharmaceutica Nv | Quinolinyl modulators of ror.gamma.t |
| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| US9328095B2 (en) | 2013-10-15 | 2016-05-03 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORgammat |
| US10028503B2 (en) | 2014-06-18 | 2018-07-24 | Children's Hospital Medical Center | Platelet storage methods and compositions for same |
| WO2017096165A1 (en) | 2015-12-03 | 2017-06-08 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
| CN108003150A (zh) * | 2016-10-31 | 2018-05-08 | 河南工业大学 | 4-杂芳基喹啉酮衍生物的制备方法及其应用 |
| KR20210038906A (ko) | 2018-07-26 | 2021-04-08 | 스미토모 다이니폰 파마 온콜로지, 인크. | 비정상적 acvr1 발현과 연관된 질환을 치료하는 방법 및 그에 사용하기 위한 acvr1 억제제 |
| HUE072069T2 (hu) | 2019-02-12 | 2025-10-28 | Sumitomo Pharma America Inc | 2-((1R,4R)-4-((3-(3-(trifluormetil)fenil)imidazo[1,2- b]piridazin-6-il)amino)ciklohexil)propán-2-ol sósavas sójának kristályos formája |
| CN114450027A (zh) | 2019-08-16 | 2022-05-06 | 儿童医院医疗中心 | 用cdc42特异性抑制剂治疗受试者的方法 |
| WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2732531A1 (de) * | 1977-07-19 | 1979-02-01 | Hoechst Ag | Imidazolcarbonsaeuren und deren derivate |
| US4835154A (en) * | 1987-06-01 | 1989-05-30 | Smithkline Beckman Corporation | 1-aralykyl-5-piperazinylmethyl-2-mercaptoimidazoles and 2-alkylthioimidazoles and their use as dopamine-βhydroxylase inhibitors |
| US5136085A (en) * | 1990-11-28 | 1992-08-04 | Glaxo Inc. | Synthesis of 2-aminobenzophenones |
| US5053543A (en) * | 1990-11-28 | 1991-10-01 | Glaxo Inc. | Synthesis of 2-aminobenzophenones |
| TW349948B (en) | 1995-10-31 | 1999-01-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 2-quinolone derivatives |
| DE69635966T2 (de) * | 1995-12-08 | 2006-11-30 | Janssen Pharmaceutica N.V. | (Imidazol-5-yl)Methyl-2-Chinolinonderivate als Farnesyl Protein transferase Inhibitoren |
| IL133212A (en) * | 1997-06-02 | 2005-12-18 | Janssen Pharmaceutica Nv | History of use (imidazolil-5-yl) methyl-2-quinolinone that act as culture inhibitors of smooth muscle cells |
| KR20010072991A (ko) | 1998-08-27 | 2001-07-31 | 실버스타인 아써 에이. | 항암제로서 유용한 알키닐-치환된 퀴놀린-2-온 유도체 |
| TR200201296T2 (tr) * | 1999-02-11 | 2002-07-22 | Pfizer Products Inc. | Antikanser maddeleri olarak faydalı heteroaril-ikame edilmiş kinolin-2-on türevleri |
-
2000
- 2000-02-04 TR TR2002/01296T patent/TR200201296T2/xx unknown
- 2000-02-04 HR HR20010574A patent/HRP20010574A2/hr not_active Application Discontinuation
- 2000-02-04 ID IDW00200101724A patent/ID29584A/id unknown
- 2000-02-04 JP JP2000598494A patent/JP4090200B2/ja not_active Expired - Fee Related
- 2000-02-04 EA EA200100766A patent/EA200100766A1/ru unknown
- 2000-02-04 DE DE60020812T patent/DE60020812T2/de not_active Expired - Lifetime
- 2000-02-04 EP EP00901292A patent/EP1150973B1/en not_active Expired - Lifetime
- 2000-02-04 PL PL00349839A patent/PL349839A1/xx not_active Application Discontinuation
- 2000-02-04 AT AT00901292T patent/ATE297916T1/de not_active IP Right Cessation
- 2000-02-04 AP APAP/P/2001/002241A patent/AP2001002241A0/en unknown
- 2000-02-04 TR TR2002/01297T patent/TR200201297T2/xx unknown
- 2000-02-04 SK SK1100-2001A patent/SK11002001A3/sk unknown
- 2000-02-04 CN CN00803668A patent/CN1340051A/zh active Pending
- 2000-02-04 WO PCT/IB2000/000121 patent/WO2000047574A1/en not_active Ceased
- 2000-02-04 EE EEP200100425A patent/EE200100425A/xx unknown
- 2000-02-04 AU AU21248/00A patent/AU2124800A/en not_active Abandoned
- 2000-02-04 CA CA002362394A patent/CA2362394C/en not_active Expired - Fee Related
- 2000-02-04 KR KR1020017010187A patent/KR20010102073A/ko not_active Ceased
- 2000-02-04 BR BR0008202-3A patent/BR0008202A/pt not_active IP Right Cessation
- 2000-02-04 OA OA1200100212A patent/OA11833A/en unknown
- 2000-02-04 ES ES00901292T patent/ES2243228T3/es not_active Expired - Lifetime
- 2000-02-04 IL IL14430700A patent/IL144307A0/xx unknown
- 2000-02-04 CZ CZ20012910A patent/CZ20012910A3/cs unknown
- 2000-02-04 HK HK02104118.7A patent/HK1042096A1/zh unknown
- 2000-02-04 HU HU0105231A patent/HUP0105231A3/hu unknown
- 2000-02-09 MA MA25905A patent/MA26718A1/fr unknown
- 2000-02-09 CO CO00008430A patent/CO5140097A1/es unknown
- 2000-02-09 HN HN2000000019A patent/HN2000000019A/es unknown
- 2000-02-09 TN TNTNSN00028A patent/TNSN00028A1/fr unknown
- 2000-02-09 US US09/501,163 patent/US6258824B1/en not_active Expired - Fee Related
- 2000-02-09 DZ DZ000021A patent/DZ3009A1/xx active
- 2000-02-10 GT GT200000014A patent/GT200000014A/es unknown
- 2000-02-10 SV SV2000000020A patent/SV2001000020A/es not_active Application Discontinuation
- 2000-02-10 PE PE2000000103A patent/PE20001464A1/es not_active Application Discontinuation
- 2000-02-10 AR ARP000100589A patent/AR028985A1/es not_active Application Discontinuation
- 2000-02-10 PA PA20008490601A patent/PA8490601A1/es unknown
-
2001
- 2001-04-17 US US09/836,026 patent/US6388092B2/en not_active Expired - Fee Related
- 2001-07-10 IS IS5997A patent/IS5997A/is unknown
- 2001-08-08 ZA ZA200106520A patent/ZA200106520B/en unknown
- 2001-08-10 NO NO20013909A patent/NO20013909L/no not_active Application Discontinuation
- 2001-08-30 BG BG105860A patent/BG105860A/xx unknown
-
2002
- 2002-03-07 US US10/092,744 patent/US6710209B2/en not_active Expired - Fee Related
-
2004
- 2004-02-05 JP JP2004029709A patent/JP4216740B2/ja not_active Expired - Fee Related
- 2004-07-20 JP JP2004211298A patent/JP2005002124A/ja active Pending
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 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4216740B2 (ja) | 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 | |
| US6479513B2 (en) | Anticancer compound and enantiomer separation method useful for synthesizing said compound | |
| US6596735B1 (en) | Quinoline derivatives useful for inhibiting farnesyl protein transferase | |
| US6844357B2 (en) | Substituted quinolin-2-one derivatives useful as antiproliferative agents | |
| JP4551771B2 (ja) | 抗増殖剤として有効な新規ベンゾイミダゾール誘導体 | |
| US6495564B1 (en) | Quinolin-2-one derivatives useful as anticancer agents | |
| JP2002511054A (ja) | ファルネシル蛋白トランスフェラーゼ阻害薬 | |
| CA2586175C (en) | Anticancer compound and enantiomer separation method useful for synthesizing said compound | |
| MXPA01008154A (en) | Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents | |
| ZA200501353B (en) | Novel benzoimidazole derivatives useful as antiproliferative agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040205 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20040319 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040720 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20040804 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20040917 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20071221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071226 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20071227 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080226 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110307 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110307 Year of fee payment: 3 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110307 Year of fee payment: 3 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110307 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120307 Year of fee payment: 4 |
|
| LAPS | Cancellation because of no payment of annual fees |