SK284943B6 - Nesteroidné (hetero)cyklicky substituované acylanilidy so zmesovým gestagénnym a androgénnym účinkom a spôsob ich výroby - Google Patents
Nesteroidné (hetero)cyklicky substituované acylanilidy so zmesovým gestagénnym a androgénnym účinkom a spôsob ich výroby Download PDFInfo
- Publication number
- SK284943B6 SK284943B6 SK1609-99A SK160999A SK284943B6 SK 284943 B6 SK284943 B6 SK 284943B6 SK 160999 A SK160999 A SK 160999A SK 284943 B6 SK284943 B6 SK 284943B6
- Authority
- SK
- Slovakia
- Prior art keywords
- methyl
- racemate
- hydroxy
- trifluoromethyl
- phthalide
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 125000005842 heteroatom Chemical group 0.000 title claims abstract description 4
- 239000000583 progesterone congener Substances 0.000 title description 10
- 230000000694 effects Effects 0.000 title description 6
- 239000003098 androgen Substances 0.000 title description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 69
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 9
- 125000005843 halogen group Chemical group 0.000 claims abstract description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 131
- -1 hydroxy, methoxy Chemical group 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000001246 bromo group Chemical group Br* 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- MIWUNJGJUSWHTO-UHFFFAOYSA-N 2-hydroxy-2,4-dimethyl-n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-4-phenylpentanamide Chemical compound C1=C2C(C)=NOC(=O)C2=CC=C1NC(=O)C(C)(O)CC(C)(C)C1=CC=CC=C1 MIWUNJGJUSWHTO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- OBBFRGLSKUBWLV-UHFFFAOYSA-N 5-[[2-hydroxy-4-phenyl-2-(trifluoromethyl)pentyl]amino]-3h-2-benzofuran-1-one Chemical compound C=1C=C2C(=O)OCC2=CC=1NCC(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 OBBFRGLSKUBWLV-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 239000007818 Grignard reagent Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 150000004795 grignard reagents Chemical class 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- PLCAABVVJJBUAK-UHFFFAOYSA-N n-(4-bromo-1-oxo-3h-2-benzofuran-5-yl)-2-hydroxy-4-methyl-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=C(Br)C=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 PLCAABVVJJBUAK-UHFFFAOYSA-N 0.000 claims description 4
- XAMPNAQSBHAKFN-UHFFFAOYSA-N n-(6-acetyl-1-oxo-3h-2-benzofuran-5-yl)-2-hydroxy-4-methyl-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound CC(=O)C1=CC=2C(=O)OCC=2C=C1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 XAMPNAQSBHAKFN-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- PLVFZQGMURDXFJ-UHFFFAOYSA-N 2-hydroxy-4,4-dimethyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)hex-5-enamide Chemical compound C=CC(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C2C(=O)OCC2=C1 PLVFZQGMURDXFJ-UHFFFAOYSA-N 0.000 claims description 3
- QLUBLXFYVSMPSA-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxy-5-methylphenyl)-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound CC1=CC=C(O)C(C(C)(C)CC(O)(C(=O)NC=2C=C3COC(=O)C3=CC=2)C(F)(F)F)=C1 QLUBLXFYVSMPSA-UHFFFAOYSA-N 0.000 claims description 3
- XQWVCRMHQFWIJK-UHFFFAOYSA-N 2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(1,1,2,2,2-pentafluoroethyl)-4-phenylpentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)C(F)(F)F)CC(C)(C)C1=CC=CC=C1 XQWVCRMHQFWIJK-UHFFFAOYSA-N 0.000 claims description 3
- CJUROHVGRLRDPO-UHFFFAOYSA-N 2-hydroxy-n-[6-(3-hydroxy-3-methylbut-1-ynyl)-1-oxo-3h-2-benzofuran-5-yl]-4-methyl-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound CC(C)(O)C#CC1=CC=2C(=O)OCC=2C=C1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 CJUROHVGRLRDPO-UHFFFAOYSA-N 0.000 claims description 3
- ZKRSCUZAXZGZEH-UHFFFAOYSA-N 4-(3-chloro-4-methoxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C1=C(Cl)C(OC)=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 ZKRSCUZAXZGZEH-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- GNHYCJPMLVTXIS-UHFFFAOYSA-N n-(6-bromo-1-oxo-3h-2-benzofuran-5-yl)-2-hydroxy-4-methyl-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=2COC(=O)C=2C=C(Br)C=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 GNHYCJPMLVTXIS-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- XBBMTLDJZXQHKN-UHFFFAOYSA-N 2,3-benzoxazin-1-one Chemical compound C1=CC=C2C(=O)ON=CC2=C1 XBBMTLDJZXQHKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- BPBUAOIZTSGINR-UHFFFAOYSA-N 2-hydroxy-4-(2-methoxyphenyl)-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound COC1=CC=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 BPBUAOIZTSGINR-UHFFFAOYSA-N 0.000 claims description 2
- BLTQUBIYGAFBBY-UHFFFAOYSA-N 2-hydroxy-4-(2-methoxyphenyl)-4-methyl-n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide Chemical compound COC1=CC=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C2C(=O)ON=C(C)C2=C1 BLTQUBIYGAFBBY-UHFFFAOYSA-N 0.000 claims description 2
- GKOISAITVMDQGW-UHFFFAOYSA-N 2-hydroxy-4-methyl-n-[1-oxo-4-(trifluoromethyl)-2,3-benzoxazin-6-yl]-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C(C(ON=C2C(F)(F)F)=O)C2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 GKOISAITVMDQGW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- WXSZIQKPURGKJK-UHFFFAOYSA-N 3,3,3-trifluoro-2-hydroxy-n-(1-oxo-3h-2-benzofuran-5-yl)-2-[(1-phenylcyclobutyl)methyl]propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(C(F)(F)F)(O)CC1(C=2C=CC=CC=2)CCC1 WXSZIQKPURGKJK-UHFFFAOYSA-N 0.000 claims description 2
- DZWVTFQWHLYZEQ-UHFFFAOYSA-N 3,3,3-trifluoro-2-hydroxy-n-(1-oxo-3h-2-benzofuran-5-yl)-2-[(1-phenylcyclohexyl)methyl]propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(C(F)(F)F)(O)CC1(C=2C=CC=CC=2)CCCCC1 DZWVTFQWHLYZEQ-UHFFFAOYSA-N 0.000 claims description 2
- NXPOOHHYDLOLJC-UHFFFAOYSA-N 4-(4-cyanophenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(C#N)C=C1 NXPOOHHYDLOLJC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- QIWBOEDTKSADTA-UHFFFAOYSA-N 5-[[4-(3-fluorophenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino]-3H-2-benzofuran-1-one Chemical compound FC=1C=C(C=CC1)C(CC(CNC=1C=C2COC(=O)C2=CC1)(C(F)(F)F)O)(C)C QIWBOEDTKSADTA-UHFFFAOYSA-N 0.000 claims description 2
- QNDBLFHVAMTSHZ-UHFFFAOYSA-N 5-[[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino]-3h-2-benzofuran-1-one Chemical compound C=1C=C2C(=O)OCC2=CC=1NCC(O)(C(F)(F)F)CC(C)(C)C1=CC(F)=CC=C1O QNDBLFHVAMTSHZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 150000004673 fluoride salts Chemical class 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- KGLJRRLKPPYOCC-UHFFFAOYSA-N n-(4-ethyl-1-oxo-2,3-benzoxazin-6-yl)-2-hydroxy-4-methyl-4-(4-methylphenyl)-2-(trifluoromethyl)pentanamide Chemical compound C1=C2C(CC)=NOC(=O)C2=CC=C1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(C)C=C1 KGLJRRLKPPYOCC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- RWPQPKDKLPQMOY-UHFFFAOYSA-N 2-hydroxy-4-(2-methoxy-5-methylphenyl)-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound COC1=CC=C(C)C=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 RWPQPKDKLPQMOY-UHFFFAOYSA-N 0.000 claims 1
- JKXKUNVXIQAJFN-UHFFFAOYSA-N 2-hydroxy-4-methyl-4-(3-methylphenyl)-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound CC1=CC=CC(C(C)(C)CC(O)(C(=O)NC=2C=C3COC(=O)C3=CC=2)C(F)(F)F)=C1 JKXKUNVXIQAJFN-UHFFFAOYSA-N 0.000 claims 1
- ALGMWCHRJYAMPE-UHFFFAOYSA-N 2-hydroxy-4-methyl-4-(4-methylphenyl)-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C1=CC(C)=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 ALGMWCHRJYAMPE-UHFFFAOYSA-N 0.000 claims 1
- JYVLIDXNZAXMDK-UHFFFAOYSA-N 2-pentanol Substances CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 claims 1
- ILPSKZIMJPXIAX-UHFFFAOYSA-N 3,3,3-trifluoro-2-hydroxy-n-(1-oxo-3h-2-benzofuran-5-yl)-2-[(1-phenylcyclopropyl)methyl]propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(C(F)(F)F)(O)CC1(C=2C=CC=CC=2)CC1 ILPSKZIMJPXIAX-UHFFFAOYSA-N 0.000 claims 1
- UFFGAJPPZBDQPK-UHFFFAOYSA-N 4-(2-fluoro-4-methoxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound FC1=CC(OC)=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 UFFGAJPPZBDQPK-UHFFFAOYSA-N 0.000 claims 1
- PMUREGUVCLMOBE-UHFFFAOYSA-N 4-(3-fluoro-4-methoxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C1=C(F)C(OC)=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 PMUREGUVCLMOBE-UHFFFAOYSA-N 0.000 claims 1
- YMMMILOIDGFPPJ-UHFFFAOYSA-N 4-(4-bromophenyl)-2-hydroxy-4-methyl-N-(1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide Chemical compound BrC1=CC=C(C=C1)C(CC(C(=O)NC=1C=CC2=C(C=NOC2=O)C1)(C(F)(F)F)O)(C)C YMMMILOIDGFPPJ-UHFFFAOYSA-N 0.000 claims 1
- WUXTURZHMMFRPK-UHFFFAOYSA-N 4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC(F)=CC=C1O WUXTURZHMMFRPK-UHFFFAOYSA-N 0.000 claims 1
- DAYFWNQOWUPASA-UHFFFAOYSA-N 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound COC1=CC=C(F)C=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 DAYFWNQOWUPASA-UHFFFAOYSA-N 0.000 claims 1
- GIBZLWRPPUSMTC-UHFFFAOYSA-N 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide Chemical compound COC1=CC=C(F)C=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C2C(=O)ON=C(C)C2=C1 GIBZLWRPPUSMTC-UHFFFAOYSA-N 0.000 claims 1
- TYIMHHDFFVFIIR-UHFFFAOYSA-N 5-[[4-(3-fluoro-4-hydroxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino]-3H-2-benzofuran-1-one Chemical compound FC=1C=C(C=CC1O)C(CC(CNC=1C=C2COC(=O)C2=CC1)(C(F)(F)F)O)(C)C TYIMHHDFFVFIIR-UHFFFAOYSA-N 0.000 claims 1
- XBVAUUNBWQQMFT-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino]-3h-2-benzofuran-1-one Chemical compound C=1C=C2C(=O)OCC2=CC=1NCC(O)(C(F)(F)F)CC(C)(C)C1=CC=C(F)C=C1 XBVAUUNBWQQMFT-UHFFFAOYSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 101150065749 Churc1 gene Proteins 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- LBCRQMLJHGVMGE-UHFFFAOYSA-N N-(4-ethyl-1-oxo-2,3-benzoxazin-6-yl)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanamide Chemical compound C(C)C1=NOC(C2=C1C=C(C=C2)NC(C(CC(C)(C)C2=C(C(=CC=C2)F)OC)(C(F)(F)F)O)=O)=O LBCRQMLJHGVMGE-UHFFFAOYSA-N 0.000 claims 1
- 229910001515 alkali metal fluoride Inorganic materials 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 7
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000012071 phase Substances 0.000 description 25
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 230000003152 gestagenic effect Effects 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- BWWXMPLQHHWEJJ-UHFFFAOYSA-N n-(4-bromo-1-oxo-3h-2-benzofuran-5-yl)-4-methyl-2-oxo-4-phenylpentanamide Chemical compound C=1C=C2C(=O)OCC2=C(Br)C=1NC(=O)C(=O)CC(C)(C)C1=CC=CC=C1 BWWXMPLQHHWEJJ-UHFFFAOYSA-N 0.000 description 12
- ISMUWQMUWFPFBZ-UHFFFAOYSA-N 5-amino-3h-2-benzofuran-1-one Chemical compound NC1=CC=C2C(=O)OCC2=C1 ISMUWQMUWFPFBZ-UHFFFAOYSA-N 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 230000001548 androgenic effect Effects 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- 239000000262 estrogen Substances 0.000 description 7
- 229940011871 estrogen Drugs 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 125000002755 pyrazolinyl group Chemical group 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- UCBIAWCJKKOAHL-UHFFFAOYSA-N 2-hydroxy-4-phenyl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 UCBIAWCJKKOAHL-UHFFFAOYSA-N 0.000 description 5
- QWHVQTQEOKGYQN-UHFFFAOYSA-N 2-oxo-3-(1-phenylcyclobutyl)propanoic acid Chemical compound C=1C=CC=CC=1C1(CC(=O)C(=O)O)CCC1 QWHVQTQEOKGYQN-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000035558 fertility Effects 0.000 description 5
- 238000007127 saponification reaction Methods 0.000 description 5
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 229960002568 ethinylestradiol Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 230000003637 steroidlike Effects 0.000 description 4
- MNAGFAFUEYEGAO-UHFFFAOYSA-N 2-(2-phenylpropyl)-2-(trifluoromethyl)oxirane Chemical compound C=1C=CC=CC=1C(C)CC1(C(F)(F)F)CO1 MNAGFAFUEYEGAO-UHFFFAOYSA-N 0.000 description 3
- SZUYDMXQRZFCLL-UHFFFAOYSA-N 2-hydroxy-4-methyl-4-thiophen-2-yl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CS1 SZUYDMXQRZFCLL-UHFFFAOYSA-N 0.000 description 3
- KOHIRGKFYXUZPB-UHFFFAOYSA-N 3-[1-(2-methoxyphenyl)cyclopropyl]-2-oxopropanoic acid Chemical compound COC1=CC=CC=C1C1(CC(=O)C(O)=O)CC1 KOHIRGKFYXUZPB-UHFFFAOYSA-N 0.000 description 3
- JQFGKPKESVXEOM-UHFFFAOYSA-N 4-methyl-2-oxo-4-phenylpentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=CC=C1 JQFGKPKESVXEOM-UHFFFAOYSA-N 0.000 description 3
- ZQHDMZVMPFNTGG-UHFFFAOYSA-N 5-amino-4-bromo-3h-2-benzofuran-1-one Chemical compound NC1=CC=C2C(=O)OCC2=C1Br ZQHDMZVMPFNTGG-UHFFFAOYSA-N 0.000 description 3
- JEONCVFTVUCPGE-UHFFFAOYSA-N 6-amino-4-methyl-2,3-benzoxazin-1-one Chemical compound C1=C(N)C=C2C(C)=NOC(=O)C2=C1 JEONCVFTVUCPGE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- BETZUBGHZNTPDP-UHFFFAOYSA-N [2-hydroxy-4-phenyl-2-(trifluoromethyl)pentyl] 4-methylbenzenesulfonate Chemical compound C=1C=CC=CC=1C(C)CC(O)(C(F)(F)F)COS(=O)(=O)C1=CC=C(C)C=C1 BETZUBGHZNTPDP-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- ABBZJHFBQXYTLU-UHFFFAOYSA-N but-3-enamide Chemical compound NC(=O)CC=C ABBZJHFBQXYTLU-UHFFFAOYSA-N 0.000 description 3
- HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 239000003433 contraceptive agent Substances 0.000 description 3
- 230000002254 contraceptive effect Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000002657 hormone replacement therapy Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- YMOWIYPUIBQBFF-UHFFFAOYSA-N n-(6-bromo-1-oxo-3h-2-benzofuran-5-yl)-4-methyl-2-oxo-4-phenylpentanamide Chemical compound C=1C=2COC(=O)C=2C=C(Br)C=1NC(=O)C(=O)CC(C)(C)C1=CC=CC=C1 YMOWIYPUIBQBFF-UHFFFAOYSA-N 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- GDEAUCMWYHCGMG-UHFFFAOYSA-N 1,1,1-trifluoro-2-[[4-nitro-3-(trifluoromethyl)anilino]methyl]-4-phenylpentan-2-ol Chemical compound C=1C=CC=CC=1C(C)CC(O)(C(F)(F)F)CNC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 GDEAUCMWYHCGMG-UHFFFAOYSA-N 0.000 description 2
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 2
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
- FTUIRGSMUVXOLJ-UHFFFAOYSA-N 2-hydroxy-4-methyl-4-phenyl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 FTUIRGSMUVXOLJ-UHFFFAOYSA-N 0.000 description 2
- ZSTGRXUVSAGLDR-UHFFFAOYSA-N 2-hydroxy-4-methyl-4-thiophen-3-yl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)(C)C=1C=CSC=1 ZSTGRXUVSAGLDR-UHFFFAOYSA-N 0.000 description 2
- NUQZUPSHGUAFLM-UHFFFAOYSA-N 2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-4-thiophen-2-yl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CS1 NUQZUPSHGUAFLM-UHFFFAOYSA-N 0.000 description 2
- CEBKHWWANWSNTI-UHFFFAOYSA-N 2-methylbut-3-yn-2-ol Chemical compound CC(C)(O)C#C CEBKHWWANWSNTI-UHFFFAOYSA-N 0.000 description 2
- JRGBQNMHOKJNTD-UHFFFAOYSA-N 2-oxo-3-(1-phenylcyclopropyl)propanoic acid Chemical compound C=1C=CC=CC=1C1(CC(=O)C(=O)O)CC1 JRGBQNMHOKJNTD-UHFFFAOYSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- XVTAQSGZOGYIEY-UHFFFAOYSA-N 3,4-dihydroisocoumarin Chemical compound C1=CC=C2C(=O)OCCC2=C1 XVTAQSGZOGYIEY-UHFFFAOYSA-N 0.000 description 2
- OEIOKPQWHXSUCH-UHFFFAOYSA-N 3-amino-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(N)OC(=O)C2=C1 OEIOKPQWHXSUCH-UHFFFAOYSA-N 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- ILZYOUAFELGUSF-UHFFFAOYSA-N 3-methylbenzotriazol-5-amine Chemical compound C1=C(N)C=C2N(C)N=NC2=C1 ILZYOUAFELGUSF-UHFFFAOYSA-N 0.000 description 2
- MUFKYUFKPCKWFQ-UHFFFAOYSA-N 4,4-dimethyl-2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)hex-5-enamide Chemical compound C=CC(C)(C)CC(=O)C(=O)NC1=CC=C2C(=O)OCC2=C1 MUFKYUFKPCKWFQ-UHFFFAOYSA-N 0.000 description 2
- XSJPLFYKYMURJY-UHFFFAOYSA-N 4,4-dimethyl-2-oxohex-5-enoic acid Chemical compound C=CC(C)(C)CC(=O)C(O)=O XSJPLFYKYMURJY-UHFFFAOYSA-N 0.000 description 2
- FWFKZBPRWVSXBK-UHFFFAOYSA-N 4-(3-methoxyphenyl)-4-methyl-2-oxopentanoic acid Chemical compound COC1=CC=CC(C(C)(C)CC(=O)C(O)=O)=C1 FWFKZBPRWVSXBK-UHFFFAOYSA-N 0.000 description 2
- KRRATTKMDZQNGX-UHFFFAOYSA-N 4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxopentanoic acid Chemical compound COC1=CC(I)=CC=C1C(C)(C)CC(=O)C(O)=O KRRATTKMDZQNGX-UHFFFAOYSA-N 0.000 description 2
- CYZBQOCHXKDBOA-UHFFFAOYSA-N 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound COC1=CC=C(F)C=C1C(C)(C)CC(O)(C(O)=O)C(F)(F)F CYZBQOCHXKDBOA-UHFFFAOYSA-N 0.000 description 2
- AQBXIOGPHBWBFP-UHFFFAOYSA-N 4-amino-2-bromobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C(Br)=C1 AQBXIOGPHBWBFP-UHFFFAOYSA-N 0.000 description 2
- ZQUORFZTZDIZSU-UHFFFAOYSA-N 4-bromo-5-nitro-3h-2-benzofuran-1-one Chemical compound [O-][N+](=O)C1=CC=C2C(=O)OCC2=C1Br ZQUORFZTZDIZSU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 150000002084 enol ethers Chemical class 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 230000001076 estrogenic effect Effects 0.000 description 2
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 2
- OUJRZMYAWPFRSV-UHFFFAOYSA-N ethyl 2-hydroxy-4-methyl-2-(trifluoromethyl)pent-4-enoate Chemical compound CCOC(=O)C(O)(C(F)(F)F)CC(C)=C OUJRZMYAWPFRSV-UHFFFAOYSA-N 0.000 description 2
- OZGYGVZLQYNNNN-UHFFFAOYSA-N ethyl 2-oxo-4-phenylpentanoate Chemical compound CCOC(=O)C(=O)CC(C)C1=CC=CC=C1 OZGYGVZLQYNNNN-UHFFFAOYSA-N 0.000 description 2
- AXFJMVYMYLLDNO-UHFFFAOYSA-N ethyl 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoate Chemical compound CCOC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC(F)=CC=C1OC AXFJMVYMYLLDNO-UHFFFAOYSA-N 0.000 description 2
- 239000011790 ferrous sulphate Substances 0.000 description 2
- 235000003891 ferrous sulphate Nutrition 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- KYTBJUQYHHTXGY-UHFFFAOYSA-N n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-oxo-3-(1-phenylcyclopropyl)propanamide Chemical compound C1=C2C(C)=NOC(=O)C2=CC=C1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CC1 KYTBJUQYHHTXGY-UHFFFAOYSA-N 0.000 description 2
- DNXXUUPUQXSUFH-UHFFFAOYSA-N neophyl chloride Chemical compound ClCC(C)(C)C1=CC=CC=C1 DNXXUUPUQXSUFH-UHFFFAOYSA-N 0.000 description 2
- 229950006098 orthocaine Drugs 0.000 description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 239000000044 progesterone antagonist Substances 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
- 229940005605 valeric acid Drugs 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- OZHWXRNMIHHRCJ-UQCQJGFQSA-N (9r,10s,13r)-13-methyl-1,2,3,4,5,6,9,10,11,12-decahydrocyclopenta[a]phenanthrene-3-sulfonamide Chemical class C([C@@H]12)CC(S(N)(=O)=O)CC1CC=C1[C@@H]2CC[C@@]2(C)C1=CC=C2 OZHWXRNMIHHRCJ-UQCQJGFQSA-N 0.000 description 1
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- BXLRLFDGLUSGQD-UHFFFAOYSA-N 1-bromo-4,5-dimethyl-2-nitrobenzene Chemical group CC1=CC(Br)=C([N+]([O-])=O)C=C1C BXLRLFDGLUSGQD-UHFFFAOYSA-N 0.000 description 1
- SXVRSCIZJBGJGB-UHFFFAOYSA-N 1-chloropropan-2-ylbenzene Chemical compound ClCC(C)C1=CC=CC=C1 SXVRSCIZJBGJGB-UHFFFAOYSA-N 0.000 description 1
- VIPWUFMFHBIKQI-UHFFFAOYSA-N 1-fluoro-4-methoxybenzene Chemical compound COC1=CC=C(F)C=C1 VIPWUFMFHBIKQI-UHFFFAOYSA-N 0.000 description 1
- UHPDGGAYPGKHSG-UHFFFAOYSA-N 1-phenyl-5-(1-phenyltetrazol-5-yl)oxytetrazole Chemical compound N=1N=NN(C=2C=CC=CC=2)C=1OC1=NN=NN1C1=CC=CC=C1 UHPDGGAYPGKHSG-UHFFFAOYSA-N 0.000 description 1
- ITHZGJVAQFFNCZ-UHFFFAOYSA-N 1-phenylcyclopentan-1-ol Chemical compound C=1C=CC=CC=1C1(O)CCCC1 ITHZGJVAQFFNCZ-UHFFFAOYSA-N 0.000 description 1
- JRJPKRSKPOCUEV-UHFFFAOYSA-N 2,1,3-benzothiadiazol-5-amine Chemical compound C1=C(N)C=CC2=NSN=C21 JRJPKRSKPOCUEV-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- DWJKILXTMUGXOU-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1CC#N DWJKILXTMUGXOU-UHFFFAOYSA-N 0.000 description 1
- HRUFSRNDFLZZRI-UHFFFAOYSA-N 2-[ethylperoxy(hydroxy)phosphoryl]acetic acid Chemical compound CCOOP(O)(=O)CC(O)=O HRUFSRNDFLZZRI-UHFFFAOYSA-N 0.000 description 1
- CEXGTXNIIFSPSF-UHFFFAOYSA-N 2-bromo-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1Br CEXGTXNIIFSPSF-UHFFFAOYSA-N 0.000 description 1
- RNDADEAFZPBMJQ-UHFFFAOYSA-N 2-bromo-6-ethoxycarbonyl-3-nitrobenzoic acid Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(Br)=C1C(O)=O RNDADEAFZPBMJQ-UHFFFAOYSA-N 0.000 description 1
- ZPZZWEDXZBXDNZ-UHFFFAOYSA-N 2-hydroxy-4-(4-methoxy-3-nitrophenyl)-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound COC1=CC=C(C(C)(C)CC(O)(C(O)=O)C(F)(F)F)C=C1[N+]([O-])=O ZPZZWEDXZBXDNZ-UHFFFAOYSA-N 0.000 description 1
- PLMJTSYTMPIPBW-UHFFFAOYSA-N 2-hydroxy-4-methyl-3-thiophen-3-yl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(C(=O)O)(C(C(C)C)C1=CSC=C1)C(F)(F)F PLMJTSYTMPIPBW-UHFFFAOYSA-N 0.000 description 1
- ZHQKXBKTPFWDBO-UHFFFAOYSA-N 2-hydroxy-4-methyl-N-(1-oxo-3H-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound OC(C(=O)NC=1C=C2COC(=O)C2=CC1)(CC(C)C)C(F)(F)F ZHQKXBKTPFWDBO-UHFFFAOYSA-N 0.000 description 1
- KBWJWTMSXCULLR-UHFFFAOYSA-N 2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-4-thiophen-3-yl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C=1C=CSC=1 KBWJWTMSXCULLR-UHFFFAOYSA-N 0.000 description 1
- XPFWZZUUQROMGI-UHFFFAOYSA-N 2-hydroxy-4-methyl-n-[4-nitro-3-(trifluoromethyl)phenyl]-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=CC=CC=1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XPFWZZUUQROMGI-UHFFFAOYSA-N 0.000 description 1
- WLTUFOLTUJPUBM-UHFFFAOYSA-N 2-hydroxy-n-(1-oxo-3h-2-benzofuran-5-yl)-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 WLTUFOLTUJPUBM-UHFFFAOYSA-N 0.000 description 1
- SMGSCASLOXKZEW-UHFFFAOYSA-N 2-hydroxy-n-(3-methylbenzotriazol-5-yl)-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2N=NN(C)C2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 SMGSCASLOXKZEW-UHFFFAOYSA-N 0.000 description 1
- DGODLUYLRNGXIK-UHFFFAOYSA-N 2-hydroxy-n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C(C(ON=C2C)=O)C2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 DGODLUYLRNGXIK-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- XAHRAWVICALETE-UHFFFAOYSA-N 2-oxo-3-(1-phenylcyclohexyl)propanoic acid Chemical compound C=1C=CC=CC=1C1(CC(=O)C(=O)O)CCCCC1 XAHRAWVICALETE-UHFFFAOYSA-N 0.000 description 1
- SLQUZOHTQRSLBO-UHFFFAOYSA-N 2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)-3-(1-phenylcyclobutyl)propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CCC1 SLQUZOHTQRSLBO-UHFFFAOYSA-N 0.000 description 1
- ODPXKSXOHJJBBQ-UHFFFAOYSA-N 2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)-3-(1-phenylcyclohexyl)propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CCCCC1 ODPXKSXOHJJBBQ-UHFFFAOYSA-N 0.000 description 1
- PFJWJFSFMKZBRP-UHFFFAOYSA-N 2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)-3-(1-phenylcyclopentyl)propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CCCC1 PFJWJFSFMKZBRP-UHFFFAOYSA-N 0.000 description 1
- PNUYKMOMCIVLDK-UHFFFAOYSA-N 2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)-3-(1-phenylcyclopropyl)propanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CC1 PNUYKMOMCIVLDK-UHFFFAOYSA-N 0.000 description 1
- BYMWNOSOAGTTCN-UHFFFAOYSA-N 2-trimethylsilyloxypent-2-enoic acid Chemical compound CCC=C(C(O)=O)O[Si](C)(C)C BYMWNOSOAGTTCN-UHFFFAOYSA-N 0.000 description 1
- GVDJEHMDNREMFA-UHFFFAOYSA-N 3,3,3-trifluoro-2-oxopropanoic acid Chemical compound OC(=O)C(=O)C(F)(F)F GVDJEHMDNREMFA-UHFFFAOYSA-N 0.000 description 1
- FYYOTZLMLLTWAP-UHFFFAOYSA-N 3,3-dimethylpent-4-enoic acid Chemical compound C=CC(C)(C)CC(O)=O FYYOTZLMLLTWAP-UHFFFAOYSA-N 0.000 description 1
- NTKIHVHEUWEYCW-UHFFFAOYSA-N 3-bromo-1,2-dimethyl-4-nitrobenzene Chemical group CC1=CC=C([N+]([O-])=O)C(Br)=C1C NTKIHVHEUWEYCW-UHFFFAOYSA-N 0.000 description 1
- MBQRUNBMJUKYAB-UHFFFAOYSA-N 3-bromo-4-nitrophthalic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C(Br)=C1C(O)=O MBQRUNBMJUKYAB-UHFFFAOYSA-N 0.000 description 1
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 description 1
- 125000001331 3-methylbutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- RGSRIZLHFCLBPC-UHFFFAOYSA-N 4,4-dimethylhex-5-en-2-one Chemical compound CC(=O)CC(C)(C)C=C RGSRIZLHFCLBPC-UHFFFAOYSA-N 0.000 description 1
- ITYHTOVJGPCPTJ-UHFFFAOYSA-N 4-(2-iodophenyl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=CC=C1I ITYHTOVJGPCPTJ-UHFFFAOYSA-N 0.000 description 1
- KLSNDECPYAFZGC-UHFFFAOYSA-N 4-(3-bromo-4-methoxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C1=C(Br)C(OC)=CC=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 KLSNDECPYAFZGC-UHFFFAOYSA-N 0.000 description 1
- KSWYPVXSQMQQCQ-UHFFFAOYSA-N 4-(3-bromophenyl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=CC(Br)=C1 KSWYPVXSQMQQCQ-UHFFFAOYSA-N 0.000 description 1
- OBYGOTQDJJKZHR-UHFFFAOYSA-N 4-(3-chlorophenyl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=CC(Cl)=C1 OBYGOTQDJJKZHR-UHFFFAOYSA-N 0.000 description 1
- AZYIKEKKSOCATJ-UHFFFAOYSA-N 4-(3-iodophenyl)-4-methyl-2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC(C)(C)C1=CC=CC(I)=C1 AZYIKEKKSOCATJ-UHFFFAOYSA-N 0.000 description 1
- FUZYBEBUPZRTMW-UHFFFAOYSA-N 4-(3-iodophenyl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=CC(I)=C1 FUZYBEBUPZRTMW-UHFFFAOYSA-N 0.000 description 1
- ZSGNXRBSOMVTIY-UHFFFAOYSA-N 4-(4-acetyl-3-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound COC1=CC(C(C)(C)CC(O)(C(O)=O)C(F)(F)F)=CC=C1C(C)=O ZSGNXRBSOMVTIY-UHFFFAOYSA-N 0.000 description 1
- LGMFTZSDDTYSFV-UHFFFAOYSA-N 4-(4-acetylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound CC(=O)C1=CC=C(C(C)(C)CC(O)(C(O)=O)C(F)(F)F)C=C1 LGMFTZSDDTYSFV-UHFFFAOYSA-N 0.000 description 1
- OQQCCVKCEDZELR-UHFFFAOYSA-N 4-(4-bromo-2-methoxyphenyl)-2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)pentanamide Chemical compound COC1=CC(Br)=CC=C1C(C)CC(=O)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 OQQCCVKCEDZELR-UHFFFAOYSA-N 0.000 description 1
- JLBPMSVHAVRSJJ-UHFFFAOYSA-N 4-(4-bromo-2-methoxyphenyl)-2-oxopentanoic acid Chemical compound COC1=CC(Br)=CC=C1C(C)CC(=O)C(O)=O JLBPMSVHAVRSJJ-UHFFFAOYSA-N 0.000 description 1
- RUAHQASXJGQQQU-UHFFFAOYSA-N 4-(4-bromo-3-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound COC1=CC(C(C)(C)CC(O)(C(O)=O)C(F)(F)F)=CC=C1Br RUAHQASXJGQQQU-UHFFFAOYSA-N 0.000 description 1
- WZUBCFFJBUUCTE-UHFFFAOYSA-N 4-(4-bromophenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(Br)C=C1 WZUBCFFJBUUCTE-UHFFFAOYSA-N 0.000 description 1
- SPKGOYRCPARZHO-UHFFFAOYSA-N 4-(4-cyano-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound COC1=CC(C#N)=CC=C1C(C)(C)CC(O)(C(O)=O)C(F)(F)F SPKGOYRCPARZHO-UHFFFAOYSA-N 0.000 description 1
- XKSXGXJPJOJLHX-UHFFFAOYSA-N 4-(4-cyanophenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(C#N)C=C1 XKSXGXJPJOJLHX-UHFFFAOYSA-N 0.000 description 1
- VKPRSAWGFXHIEO-UHFFFAOYSA-N 4-(4-ethenylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoic acid Chemical compound OC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(C=C)C=C1 VKPRSAWGFXHIEO-UHFFFAOYSA-N 0.000 description 1
- BBHXWQQCLGDRJF-UHFFFAOYSA-N 4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)pentanamide Chemical compound COC1=CC(I)=CC=C1C(C)(C)CC(=O)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 BBHXWQQCLGDRJF-UHFFFAOYSA-N 0.000 description 1
- RLSSRKSQRFKSGY-UHFFFAOYSA-N 4-(4-iodophenyl)-4-methyl-2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC(C)(C)C1=CC=C(I)C=C1 RLSSRKSQRFKSGY-UHFFFAOYSA-N 0.000 description 1
- NXUSSDJXYUWARA-UHFFFAOYSA-N 4-(4-iodophenyl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=C(I)C=C1 NXUSSDJXYUWARA-UHFFFAOYSA-N 0.000 description 1
- OOXBRSLQDAMBIS-UHFFFAOYSA-N 4-(5-chloro-2-hydroxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC(Cl)=CC=C1O OOXBRSLQDAMBIS-UHFFFAOYSA-N 0.000 description 1
- UYXURLMCUPZVQR-UHFFFAOYSA-N 4-(5-chloro-2-methoxyphenyl)-2-hydroxy-4-methyl-n-(1-oxo-3h-2-benzofuran-5-yl)-2-(trifluoromethyl)pentanamide Chemical compound COC1=CC=C(Cl)C=C1C(C)(C)CC(O)(C(F)(F)F)C(=O)NC1=CC=C(C(=O)OC2)C2=C1 UYXURLMCUPZVQR-UHFFFAOYSA-N 0.000 description 1
- FRUVVVPJVUXQTL-UHFFFAOYSA-N 4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentanoic acid Chemical compound COC1=CC=C(F)C=C1C(C)(C)CC(=O)C(O)=O FRUVVVPJVUXQTL-UHFFFAOYSA-N 0.000 description 1
- DEUHAVMPRYKFAJ-UHFFFAOYSA-N 4-(5-fluoro-2-methoxyphenyl)-4-methyl-n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-oxopentanamide Chemical compound COC1=CC=C(F)C=C1C(C)(C)CC(=O)C(=O)NC1=CC=C2C(=O)ON=C(C)C2=C1 DEUHAVMPRYKFAJ-UHFFFAOYSA-N 0.000 description 1
- NDKYGTLERGKCEZ-UHFFFAOYSA-N 4-bromo-5-nitro-2-benzofuran-1,3-dione Chemical compound [O-][N+](=O)C1=CC=C2C(=O)OC(=O)C2=C1Br NDKYGTLERGKCEZ-UHFFFAOYSA-N 0.000 description 1
- ULPOSDMVRAOCKS-UHFFFAOYSA-N 4-ethyl-6-[[2-hydroxy-4-phenyl-2-(trifluoromethyl)pentyl]amino]-2,3-benzoxazin-1-one Chemical compound C1=C2C(CC)=NOC(=O)C2=CC=C1NCC(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 ULPOSDMVRAOCKS-UHFFFAOYSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- FCUAFMSIYBZYLQ-UHFFFAOYSA-N 4-methyl-2-oxo-n-(1-oxo-3h-2-benzofuran-5-yl)-4-phenylpentanamide Chemical compound C=1C=C2C(=O)OCC2=CC=1NC(=O)C(=O)CC(C)(C)C1=CC=CC=C1 FCUAFMSIYBZYLQ-UHFFFAOYSA-N 0.000 description 1
- SVZFNXQARITLAJ-UHFFFAOYSA-N 4-methyl-n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-oxo-4-phenylpentanamide Chemical compound C1=C2C(C)=NOC(=O)C2=CC=C1NC(=O)C(=O)CC(C)(C)C1=CC=CC=C1 SVZFNXQARITLAJ-UHFFFAOYSA-N 0.000 description 1
- GBUSGOLTSBLLGX-UHFFFAOYSA-N 4-nitro-2-(2,5,5-trimethyl-1,3-dioxan-2-yl)benzoic acid Chemical compound O1CC(C)(C)COC1(C)C1=CC([N+]([O-])=O)=CC=C1C(O)=O GBUSGOLTSBLLGX-UHFFFAOYSA-N 0.000 description 1
- AUIQUSQXFBHMMZ-UHFFFAOYSA-N 5-(2,5-dimethylpyrrol-1-yl)-3-prop-1-enyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(C=CC)OC(=O)C2=CC=C1N1C(C)=CC=C1C AUIQUSQXFBHMMZ-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- BLNBKIAQTMOAPF-UHFFFAOYSA-N 5-[[2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino]-3H-2-benzofuran-1-one Chemical compound OC(CNC=1C=C2COC(=O)C2=CC1)(CC(C)C)C(F)(F)F BLNBKIAQTMOAPF-UHFFFAOYSA-N 0.000 description 1
- HODOSJNSRPXYBH-UHFFFAOYSA-N 5-amino-2,3-dihydroinden-1-one Chemical compound NC1=CC=C2C(=O)CCC2=C1 HODOSJNSRPXYBH-UHFFFAOYSA-N 0.000 description 1
- MYSWCVKZJGXLAG-UHFFFAOYSA-N 5-amino-3-prop-1-enyl-3h-2-benzofuran-1-one Chemical compound C1=C(N)C=C2C(C=CC)OC(=O)C2=C1 MYSWCVKZJGXLAG-UHFFFAOYSA-N 0.000 description 1
- KMAINKMYXGXMMX-UHFFFAOYSA-N 5-amino-6-bromo-3h-2-benzofuran-1-one Chemical compound C1=C(Br)C(N)=CC2=C1C(=O)OC2 KMAINKMYXGXMMX-UHFFFAOYSA-N 0.000 description 1
- JCICGLDPKMRBTG-UHFFFAOYSA-N 5-bromo-6-nitro-2-benzofuran-1,3-dione Chemical compound C1=C(Br)C([N+](=O)[O-])=CC2=C1C(=O)OC2=O JCICGLDPKMRBTG-UHFFFAOYSA-N 0.000 description 1
- IUGQBNIWBLXYRM-UHFFFAOYSA-N 5-bromo-6-nitro-3h-2-benzofuran-1-one Chemical compound C1=C(Br)C([N+](=O)[O-])=CC2=C1COC2=O IUGQBNIWBLXYRM-UHFFFAOYSA-N 0.000 description 1
- DHELIGKVOGTMGF-UHFFFAOYSA-N 5-chloro-1-phenyltetrazole Chemical compound ClC1=NN=NN1C1=CC=CC=C1 DHELIGKVOGTMGF-UHFFFAOYSA-N 0.000 description 1
- BEVVUJBVEXJGKM-UHFFFAOYSA-N 6-amino-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(N)=CC=C21 BEVVUJBVEXJGKM-UHFFFAOYSA-N 0.000 description 1
- NANVMAQMQLZFGG-UHFFFAOYSA-N 6-amino-4-ethyl-2,3-benzoxazin-1-one Chemical compound C1=C(N)C=C2C(CC)=NOC(=O)C2=C1 NANVMAQMQLZFGG-UHFFFAOYSA-N 0.000 description 1
- GBPLNDKPUHVINJ-UHFFFAOYSA-N 6-bromo-5-nitro-3h-2-benzofuran-1-one Chemical compound C1=C(Br)C([N+](=O)[O-])=CC2=C1C(=O)OC2 GBPLNDKPUHVINJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102100032187 Androgen receptor Human genes 0.000 description 1
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 description 1
- FSYAYXLLKJBOLG-UHFFFAOYSA-N BrC1=C(C(=O)O)C=CC(=C1)[N+](=O)[O-].NC=1C=C2C(OC(=O)C2=CC1)C=CC Chemical compound BrC1=C(C(=O)O)C=CC(=C1)[N+](=O)[O-].NC=1C=C2C(OC(=O)C2=CC1)C=CC FSYAYXLLKJBOLG-UHFFFAOYSA-N 0.000 description 1
- UOGNZXQAHLIUPD-UHFFFAOYSA-N BrC1=C2C(OC(=O)C2=CC=C1)N Chemical compound BrC1=C2C(OC(=O)C2=CC=C1)N UOGNZXQAHLIUPD-UHFFFAOYSA-N 0.000 description 1
- CNBLSWWFXWVVEY-UHFFFAOYSA-N BrC=1C=C(C(=O)O)C(=CC1[N+](=O)[O-])C(=O)OCC Chemical compound BrC=1C=C(C(=O)O)C(=CC1[N+](=O)[O-])C(=O)OCC CNBLSWWFXWVVEY-UHFFFAOYSA-N 0.000 description 1
- 206010006298 Breast pain Diseases 0.000 description 1
- ROGFVYWDFXPWAO-UHFFFAOYSA-N C(C)C(C(C(=O)O)(C(F)(F)F)O)C(C)(C)C1=CC=C(C=C1)Br Chemical compound C(C)C(C(C(=O)O)(C(F)(F)F)O)C(C)(C)C1=CC=C(C=C1)Br ROGFVYWDFXPWAO-UHFFFAOYSA-N 0.000 description 1
- FNVPITKHFTXPKS-UHFFFAOYSA-N C1(=CC=CC=C1)C1(CCC1)C#N.C1(=CC=CC=C1)C1(CCC1)CC(C(=O)O)=O Chemical compound C1(=CC=CC=C1)C1(CCC1)C#N.C1(=CC=CC=C1)C1(CCC1)CC(C(=O)O)=O FNVPITKHFTXPKS-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 206010016807 Fluid retention Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010054834 Hypergonadism Diseases 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 208000006662 Mastodynia Diseases 0.000 description 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 1
- 101100025919 Mus musculus Ncoa6 gene Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 229920001774 Perfluoroether Polymers 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- MHXGZNAKZRVAHJ-UHFFFAOYSA-N [2-hydroxy-4-methyl-4-phenyl-2-(trifluoromethyl)pentyl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1 MHXGZNAKZRVAHJ-UHFFFAOYSA-N 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000001609 comparable effect Effects 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- PMHQVHHXPFUNSP-UHFFFAOYSA-M copper(1+);methylsulfanylmethane;bromide Chemical compound Br[Cu].CSC PMHQVHHXPFUNSP-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 1
- MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 1
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003687 estradiol congener Substances 0.000 description 1
- 150000002159 estradiols Chemical class 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- KGHMILYCSRSPIP-UHFFFAOYSA-N ethyl 2-hydroxy-4-(4-methoxyphenyl)-4-methyl-2-(trifluoromethyl)pentanoate Chemical compound CCOC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(OC)C=C1 KGHMILYCSRSPIP-UHFFFAOYSA-N 0.000 description 1
- CAALKBPWOACRAR-UHFFFAOYSA-N ethyl 2-hydroxy-4-phenyl-2-(trifluoromethyl)pentanoate Chemical compound CCOC(=O)C(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 CAALKBPWOACRAR-UHFFFAOYSA-N 0.000 description 1
- ZOVCJWPFNSHMKT-UHFFFAOYSA-N ethyl 2-trimethylsilyloxyprop-2-enoate Chemical compound CCOC(=O)C(=C)O[Si](C)(C)C ZOVCJWPFNSHMKT-UHFFFAOYSA-N 0.000 description 1
- KJHQVUNUOIEYSV-UHFFFAOYSA-N ethyl 3,3,3-trifluoro-2-oxopropanoate Chemical compound CCOC(=O)C(=O)C(F)(F)F KJHQVUNUOIEYSV-UHFFFAOYSA-N 0.000 description 1
- USCUPKCCHZTZSZ-UHFFFAOYSA-N ethyl 4-(4-ethenylphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanoate Chemical compound CCOC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=C(C=C)C=C1 USCUPKCCHZTZSZ-UHFFFAOYSA-N 0.000 description 1
- NUEIFMIVWUYAAM-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)-4-methyl-2-(trifluoromethyl)pentanoate Chemical compound C(C)OC(C(CC(C)(C)C1=CC=C(C=C1)OC)C(F)(F)F)=O NUEIFMIVWUYAAM-UHFFFAOYSA-N 0.000 description 1
- XEHVFKKSDRMODV-UHFFFAOYSA-N ethynyl Chemical compound C#[C] XEHVFKKSDRMODV-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000001794 hormone therapy Methods 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
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960004400 levonorgestrel Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- FKUUDDGRDRPAQQ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=C[C-]=C1 FKUUDDGRDRPAQQ-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- MKLKDUHMZCIBSJ-UHFFFAOYSA-N methyl 3,3-dimethylpent-4-enoate Chemical compound COC(=O)CC(C)(C)C=C MKLKDUHMZCIBSJ-UHFFFAOYSA-N 0.000 description 1
- PFBKULFLMUCFPS-UHFFFAOYSA-N methyl 4,4-dimethyl-2-oxohex-5-enoate Chemical compound COC(=O)C(=O)CC(C)(C)C=C PFBKULFLMUCFPS-UHFFFAOYSA-N 0.000 description 1
- AQUDYWFMQDSMGT-UHFFFAOYSA-N methyl 4-(3-methoxyphenyl)-4-methyl-2-oxopentanoate Chemical compound COC(=O)C(=O)CC(C)(C)C1=CC=CC(OC)=C1 AQUDYWFMQDSMGT-UHFFFAOYSA-N 0.000 description 1
- MCNOTXROWOGSGU-UHFFFAOYSA-N methyl 4-iodo-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1OC MCNOTXROWOGSGU-UHFFFAOYSA-N 0.000 description 1
- KVORUNOAOVOPGS-UHFFFAOYSA-N methyl 4-methyl-2-oxopent-3-enoate Chemical compound COC(=O)C(=O)C=C(C)C KVORUNOAOVOPGS-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 1
- XBLPTNDIRVYALA-UHFFFAOYSA-N n-(1-oxo-3h-2-benzofuran-5-yl)acetamide Chemical compound CC(=O)NC1=CC=C2C(=O)OCC2=C1 XBLPTNDIRVYALA-UHFFFAOYSA-N 0.000 description 1
- DASXGDWYSWOGAI-UHFFFAOYSA-N n-(2,1,3-benzoxadiazol-5-yl)-2-hydroxy-4-phenyl-2-(trifluoromethyl)pentanamide Chemical compound C1=CC2=NON=C2C=C1NC(=O)C(O)(C(F)(F)F)CC(C)C1=CC=CC=C1 DASXGDWYSWOGAI-UHFFFAOYSA-N 0.000 description 1
- GGKXKUXDVBOPLP-UHFFFAOYSA-N n-(4-ethyl-1-oxo-2,3-benzoxazin-6-yl)-2-hydroxy-4-(2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)pentanamide Chemical compound C1=C2C(CC)=NOC(=O)C2=CC=C1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC=C1OC GGKXKUXDVBOPLP-UHFFFAOYSA-N 0.000 description 1
- VPZWZQQXNOSXJD-UHFFFAOYSA-N n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-oxo-3-(1-phenylcyclobutyl)propanamide Chemical compound C1=C2C(C)=NOC(=O)C2=CC=C1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CCC1 VPZWZQQXNOSXJD-UHFFFAOYSA-N 0.000 description 1
- BFCQFZDTMFIDQK-UHFFFAOYSA-N n-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-oxo-3-(1-phenylcyclohexyl)propanamide Chemical compound C1=C2C(C)=NOC(=O)C2=CC=C1NC(=O)C(=O)CC1(C=2C=CC=CC=2)CCCCC1 BFCQFZDTMFIDQK-UHFFFAOYSA-N 0.000 description 1
- MIHJCLQINRFOLX-UHFFFAOYSA-N n-[4-nitro-3-(trifluoromethyl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MIHJCLQINRFOLX-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 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 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical class C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 1
- 125000005506 phthalide group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000757 progestagenic effect Effects 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000001625 seminal vesicle Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 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
- 229960003604 testosterone Drugs 0.000 description 1
- 150000003515 testosterones Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/34—Gestagens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/22—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/02—1,2-Oxazines; Hydrogenated 1,2-oxazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/08—1,2,5-Oxadiazoles; Hydrogenated 1,2,5-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/72—Benzo[c]thiophenes; Hydrogenated benzo[c]thiophenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19723722A DE19723722A1 (de) | 1997-05-30 | 1997-05-30 | Nichtsteroidale Gestagene |
| PCT/EP1998/003242 WO1998054159A1 (de) | 1997-05-30 | 1998-06-02 | Nichtsteroidale (hetero)zyklisch-substituierte acylanilide mit gemischter gestagener und androgener wirksamkeit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK160999A3 SK160999A3 (en) | 2000-07-11 |
| SK284943B6 true SK284943B6 (sk) | 2006-02-02 |
Family
ID=7831567
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1609-99A SK284943B6 (sk) | 1997-05-30 | 1998-06-02 | Nesteroidné (hetero)cyklicky substituované acylanilidy so zmesovým gestagénnym a androgénnym účinkom a spôsob ich výroby |
Country Status (30)
Families Citing this family (100)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19856475A1 (de) * | 1998-11-27 | 2000-05-31 | Schering Ag | Nichtsteroidale Entzündungshemmer |
| DE10346940B3 (de) * | 2003-10-06 | 2005-06-16 | Schering Ag | Substituierte Pentanole, ihre Verwendung zur Herstellung von Arzneimitteln speziell Entzündungshemmer sowie diese enthaltende pharmazeutische Präparate |
| DE10038639A1 (de) | 2000-07-28 | 2002-02-21 | Schering Ag | Nichtsteroidale Entzündungshemmer |
| EP1373888A2 (en) * | 2000-12-28 | 2004-01-02 | Schering Aktiengesellschaft | Method for screening for progesterone receptor isoform-specific ligands |
| EP1467982B8 (en) * | 2002-01-14 | 2007-04-11 | Boehringer Ingelheim Pharmaceuticals Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical formulations containing them, and uses thereof |
| DK1482925T3 (da) * | 2002-03-11 | 2007-05-14 | Bayer Schering Pharma Ag | 5- (2-hydroxy-3 -'1 - (3-trifluormethylphenyl) cyclopropylpropionylamino) phtalid og relaterede forbindelser med progesteronreceptormoducerende aktivitet til anvendelse i fertilitetskontrol og hormonerstatningsterapi |
| EP1344776A1 (en) * | 2002-03-11 | 2003-09-17 | Schering Aktiengesellschaft | 5- 2-hydroxy-3-[1-(3-trifluoromethylphenyl)-cyclopropyl]-propionylamino -phtalide and 6- 2-hydroxy-3-[1-(3-trifluoromethylphenyl)-cyclopropyl]-propionylamino -4-methyl-2,3-benzoxazin-1-one derivatives with progesterone receptor modulating activity for use in fertility control, hormone replacement therapy and the treatment of gynecological disorders |
| EP1490317A1 (en) | 2002-03-26 | 2004-12-29 | Boehringer Ingelheim Pharmaceuticals Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| JP4324480B2 (ja) | 2002-03-26 | 2009-09-02 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | グルココルチコイドミメティクス、その製法、医薬組成物、及び使用 |
| DE10215316C1 (de) * | 2002-04-02 | 2003-12-18 | Schering Ag | Chinolin- und Isochinolin-Derivate, ein pharmazeutisches Mittel und ihre Verwendung als Entzündungshemmer |
| US7186864B2 (en) | 2002-05-29 | 2007-03-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| US7074806B2 (en) | 2002-06-06 | 2006-07-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| CA2496175A1 (en) | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted hihydroquinolines as glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| NZ538932A (en) | 2002-08-29 | 2007-04-27 | Boehringer Ingelheim Pharma | 3-(sulfonamidoethyl)-indole derivatives for use as glucocorticoid mimetics in the treatment of inflammatory, allergic and proliferative disease |
| JP2006518328A (ja) * | 2002-10-15 | 2006-08-10 | ユニバーシティ・オブ・テネシー・リサーチ・ファウンデーション | 複素環選択的アンドロゲン受容体調節剤及びその使用方法 |
| DE10261874A1 (de) * | 2002-12-20 | 2004-07-08 | Schering Ag | Nichtsteroidale Entzündungshemmer |
| EP1583745A1 (en) | 2003-01-03 | 2005-10-12 | Boehringer Ingelheim Pharmaceuticals Inc. | 1-propanol and 1-propylamine derivatives and their use as glucocorticoid ligands |
| US20040224992A1 (en) * | 2003-02-27 | 2004-11-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| CA2531060A1 (en) * | 2003-07-01 | 2005-01-13 | Schering Aktiengesellschaft | Heterocyclically-substitued pentanol derivatives, process for their production and their use as anti-inflammatory agents |
| GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
| UY28526A1 (es) | 2003-09-24 | 2005-04-29 | Boehringer Ingelheim Pharma | Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos |
| JP4468369B2 (ja) | 2003-10-16 | 2010-05-26 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | ある種のトリフルオロメチル置換アルコールの立体選択的合成 |
| US7795272B2 (en) | 2004-03-13 | 2010-09-14 | Boehringer Ingelheim Pharmaceutical, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof |
| PE20060272A1 (es) | 2004-05-24 | 2006-05-22 | Glaxo Group Ltd | (2r,3r,4s,5r,2'r,3'r,4's,5's)-2,2'-{trans-1,4-ciclohexanodiilbis-[imino(2-{[2-(1-metil-1h-imidazol-4-il)etil]amino}-9h-purin-6,9-diil)]}bis[5-(2-etil-2h-tetrazol-5-il)tetrahidro-3,4-furanodiol] como agonista a2a |
| TWI307630B (en) | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
| DE102004062182B4 (de) * | 2004-12-20 | 2007-06-06 | Bayer Schering Pharma Ag | Transdermales Pflaster mit Progesteron A-Spezifische Liganden (PRASL) als Wirkstoff |
| PE20060776A1 (es) | 2004-12-27 | 2006-09-26 | Boehringer Ingelheim Pharma | Mimeticos de glucocorticoides, metodos para prepararlos y composiciones farmaceuticas |
| JP5281291B2 (ja) | 2005-01-10 | 2013-09-04 | グラクソ グループ リミテッド | 新規化合物 |
| WO2006083030A1 (ja) * | 2005-02-04 | 2006-08-10 | Ajinomoto Co., Inc. | 脂肪酸の製造方法および脂肪酸の塩結晶 |
| UY29439A1 (es) | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| MY145281A (en) | 2005-03-25 | 2012-01-13 | Glaxo Group Ltd | Novel compounds |
| DE102005017326A1 (de) * | 2005-04-14 | 2007-03-29 | Schering Ag | Tetrahydronaphthalinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Entzündungshemmer |
| DE102005030294A1 (de) * | 2005-06-24 | 2007-01-04 | Schering Ag | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| US7408060B2 (en) | 2005-06-24 | 2008-08-05 | Schering Ag | Nonsteroidal progesterone receptor modulators |
| DE102005030293A1 (de) * | 2005-06-24 | 2007-01-04 | Schering Ag | Verwendung von nichtsteroidale Progesteronrezeptor-Modulatoren |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| EP1963287A1 (en) | 2005-12-09 | 2008-09-03 | F.Hoffmann-La Roche Ag | Glucocorticoid receptor modulators as antiinflammatory agents |
| PE20071068A1 (es) | 2005-12-20 | 2007-12-13 | Glaxo Group Ltd | Acido 3-(4-{[4-(4-{[3-(3,3-dimetil-1-piperidinil)propil]oxi}fenil)-1-piperidinil]carbonil}-1-naftalenil)propanoico o propenoico, sales de los mismos, como antagonistas de los receptores h1 y h3 |
| EA200801997A1 (ru) | 2006-04-20 | 2009-04-28 | Глаксо Груп Лимитед | Новые соединения |
| GB0611587D0 (en) | 2006-06-12 | 2006-07-19 | Glaxo Group Ltd | Novel compounds |
| MX2009005264A (es) | 2006-12-06 | 2009-05-28 | Boehringer Ingelheim Int | Mimeticos de glucocorticoides, metodos para su fabricacion, composiciones farmaceuticas y usos de los mismos. |
| DE102007023614A1 (de) | 2007-05-21 | 2008-11-27 | Bayer Schering Pharma Aktiengesellschaft | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| DE102007049630A1 (de) | 2007-10-11 | 2009-10-29 | Bayer Schering Pharma Aktiengesellschaft | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| UY30815A1 (es) * | 2006-12-21 | 2008-07-31 | Bayer Schering Pharma Ag | Moduladores no esteroidales del receptor de progesterona |
| UY30805A1 (es) * | 2006-12-21 | 2008-07-31 | Bayer Schering Pharma Ag | Moduladores no esteroides de receptores de progesterona |
| JP5090773B2 (ja) * | 2006-12-26 | 2012-12-05 | 国立大学法人東京工業大学 | 光学活性含フッ素カルボニル−エン生成物の製造方法 |
| AR065804A1 (es) | 2007-03-23 | 2009-07-01 | Smithkline Beecham Corp | Compuesto de indol carboxamida, composicion farmaceutica que lo comprende y uso de dicho compuesto para preparar un medicamento |
| DE102007032800A1 (de) | 2007-07-10 | 2009-01-15 | Bayer Schering Pharma Aktiengesellschaft | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| DE102007058747A1 (de) | 2007-12-05 | 2009-06-10 | Bayer Schering Pharma Aktiengesellschaft | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| EP2070909A1 (de) * | 2007-12-15 | 2009-06-17 | Bayer Schering Pharma AG | Nichtsteroidale Progesteronrezeptor-Modulatoren |
| JP5791500B2 (ja) | 2008-05-23 | 2015-10-07 | パンミラ ファーマシューティカルズ，エルエルシー． | ５−リポキシゲナーゼ活性化タンパク質阻害剤 |
| WO2009147190A1 (en) | 2008-06-05 | 2009-12-10 | Glaxo Group Limited | Novel compounds |
| EP2280946B1 (en) | 2008-06-05 | 2016-02-10 | Glaxo Group Limited | 4-carboxamide indazole derivatives useful as inhibitors of p13-kinases |
| DK2300472T3 (da) | 2008-06-06 | 2012-04-10 | Boehringer Ingelheim Int | Glucocorticoidmimetika, fremgangsmåder til disses fremstilling, farmaceutiske sammensætninger samt anvendelser deraf |
| WO2010094643A1 (en) | 2009-02-17 | 2010-08-26 | Glaxo Group Limited | Quinoline derivatives and their uses for rhinitis and urticaria |
| US8524751B2 (en) | 2009-03-09 | 2013-09-03 | GlaxoSmithKline Intellecutual Property Development | 4-oxadiazol-2-YL-indazoles as inhibitors of P13 kinases |
| US8354539B2 (en) | 2009-03-10 | 2013-01-15 | Glaxo Group Limited | Indole derivatives as IKK2 inhibitors |
| JP2012520845A (ja) | 2009-03-17 | 2012-09-10 | グラクソ グループ リミテッド | Ｉｔｋ阻害剤として使用されるピリミジン誘導体 |
| US20120035247A1 (en) | 2009-03-19 | 2012-02-09 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Signal Transducer and Activator of Transcription 6 (STAT6) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| JP2012520683A (ja) | 2009-03-19 | 2012-09-10 | メルク・シャープ・エンド・ドーム・コーポレイション | 低分子干渉核酸（ｓｉＮＡ）を用いた結合組織増殖因子（ＣＴＧＦ）遺伝子発現のＲＮＡ干渉媒介性阻害 |
| AU2010226604A1 (en) | 2009-03-19 | 2011-10-13 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of BTB and CNC homology 1, basic leucine zipper transcription factor 1 (Bach 1) gene expression using short interfering nucleic acid (siNA) sequence listing |
| US20120029054A1 (en) | 2009-03-19 | 2012-02-02 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of GATA Binding Protein 3 (GATA3) Gene Expression Using Short Intefering Nucleic Acid (siNA) |
| US20120022142A1 (en) | 2009-03-27 | 2012-01-26 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Signal Transducer and Activator of Transcription 1 (STAT1) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| WO2010111468A2 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE NERVE GROWTH FACTOR BETA CHAIN (NGFß) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA) |
| WO2010111490A2 (en) | 2009-03-27 | 2010-09-30 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE THYMIC STROMAL LYMPHOPOIETIN (TSLP) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20120010272A1 (en) | 2009-03-27 | 2012-01-12 | Merck Sharp & Dohme Corp. | RNA Interference Mediated Inhibition of Apoptosis Signal-Regulating Kinase 1 (ASK1) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
| EP2411517A2 (en) | 2009-03-27 | 2012-02-01 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE INTERCELLULAR ADHESION MOLECULE 1 (ICAM-1)GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| WO2010122088A1 (en) | 2009-04-24 | 2010-10-28 | Glaxo Group Limited | Pyrazole and triazole carboxamides as crac channel inhibitors |
| US8399436B2 (en) | 2009-04-24 | 2013-03-19 | Glaxo Group Limited | N-pyrazolyl carboxamides as CRAC channel inhibitors |
| RS53830B1 (sr) | 2009-04-30 | 2015-06-30 | Glaxo Group Limited | Indazoli supstituisani oksazolom kao inhibitori pi3-kinaze |
| EP2507231A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Indazole derivatives as pi 3 - kinase inhibitors |
| WO2011067365A1 (en) | 2009-12-03 | 2011-06-09 | Glaxo Group Limited | Benzpyrazole derivatives as inhibitors of p13 kinases |
| WO2011067364A1 (en) | 2009-12-03 | 2011-06-09 | Glaxo Group Limited | Novel compounds |
| US20120272951A1 (en) | 2009-12-16 | 2012-11-01 | 3M Innovative Properties Company | Formulations and methods for controlling mdi particle size delivery |
| WO2011110575A1 (en) | 2010-03-11 | 2011-09-15 | Glaxo Group Limited | Derivatives of 2-[2-(benzo- or pyrido-) thiazolylamino]-6-aminopyridine, useful in the treatment of respiratoric, allergic or inflammatory diseases |
| GB201007203D0 (en) | 2010-04-29 | 2010-06-16 | Glaxo Group Ltd | Novel compounds |
| EP2613781B1 (en) | 2010-09-08 | 2016-08-24 | GlaxoSmithKline Intellectual Property Development Limited | Indazole derivatives for use in the treatment of influenza virus infection |
| HRP20151017T1 (hr) | 2010-09-08 | 2015-10-23 | Glaxosmithkline Intellectual Property Development Limited | Polimorfi i soli n-[5-[4-(5-{[(2r,6s)-2,6-dimetil-4-morfolinil]metil}-1,3-oksazol-2-il)-1h-indazol-6-il]-2-(metiloksi)-3-piridinil]metansulfonamida |
| WO2012035055A1 (en) | 2010-09-17 | 2012-03-22 | Glaxo Group Limited | Novel compounds |
| JP5795643B2 (ja) | 2010-10-21 | 2015-10-14 | グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ | アレルギー性状態、免疫性状態及び炎症性状態に作用するピラゾール化合物 |
| WO2012052459A1 (en) | 2010-10-21 | 2012-04-26 | Glaxo Group Limited | Pyrazole compounds acting against allergic, inflammatory and immune disorders |
| GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
| GB201104153D0 (en) | 2011-03-11 | 2011-04-27 | Glaxo Group Ltd | Novel compounds |
| US20140005188A1 (en) | 2011-03-11 | 2014-01-02 | Glaxo Group Limited | Pyrido[3,4-b]pyrazine derivatives as syk inhibitors |
| KR20160060100A (ko) | 2013-09-22 | 2016-05-27 | 칼리토르 사이언시즈, 엘엘씨 | 치환된 아미노피리미딘 화합물 및 이용 방법 |
| KR20160062179A (ko) | 2013-10-17 | 2016-06-01 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 호흡기 질병의 치료를 위한 ｐｉ３ｋ 억제제 |
| EP3057588A1 (en) | 2013-10-17 | 2016-08-24 | GlaxoSmithKline Intellectual Property Development Limited | Pi3k inhibitor for treatment of respiratory disease |
| US9399637B2 (en) | 2014-03-28 | 2016-07-26 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
| WO2015173701A2 (en) | 2014-05-12 | 2015-11-19 | Glaxosmithkline Intellectual Property (No. 2) Limited | Pharmaceutical compositions for treating infectious diseases |
| EP3347097B1 (en) | 2015-09-11 | 2021-02-24 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine derivatives as modulators of the kinases jak, flt3 and aurora |
| GB201602527D0 (en) | 2016-02-12 | 2016-03-30 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| EP3497100A1 (en) | 2016-08-08 | 2019-06-19 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds |
| GB201706102D0 (en) | 2017-04-18 | 2017-05-31 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| GB201712081D0 (en) | 2017-07-27 | 2017-09-13 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| EP3569228A1 (en) * | 2018-05-17 | 2019-11-20 | Association pour la recherche à l'IGBMC (ARI) | Non-steroidal selective glucocorticoid receptor agonistic modulators (segrams) and uses thereof |
| WO2019099311A1 (en) | 2017-11-19 | 2019-05-23 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| EP3740468B1 (en) | 2018-01-20 | 2025-12-31 | Sunshine Lake Pharma Co., Ltd. | Substituted Aminopyrimidine Compounds and Methods of Use |
| CA3173172A1 (en) | 2020-03-26 | 2021-09-30 | Christopher D. Kane | Cathepsin inhibitors for preventing or treating viral infections |
| KR20230024328A (ko) * | 2020-06-12 | 2023-02-20 | 상하이 제민케어 파마슈티칼스 컴퍼니 리미티드 | 프탈라지논 화합물, 이의 제조 방법 및 이의 의학적 용도 |
| CN114605308B (zh) * | 2022-03-18 | 2023-12-19 | 阜新孚隆宝医药科技有限公司 | 一种帕罗韦德的氮杂双环医药中间体的制备方法及中间体 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4191775A (en) * | 1977-12-15 | 1980-03-04 | Imperial Chemical Industries Limited | Amide derivatives |
| NZ197008A (en) * | 1980-05-22 | 1984-10-19 | Ici Ltd | Acylanilide derivatives and pharmaceutical compositions |
| JPS5789048A (en) * | 1980-11-20 | 1982-06-03 | Nat Jutaku Kenzai | Independent pilar with cover |
| CA1261835A (en) * | 1984-08-20 | 1989-09-26 | Masaaki Toda | (fused) benz(thio)amides |
| GB8617652D0 (en) * | 1986-07-18 | 1986-08-28 | Ici Plc | Acylanilide derivatives |
| GB8617653D0 (en) * | 1986-07-18 | 1986-08-28 | Ici Plc | Amide derivatives |
| JPH07508987A (ja) * | 1992-07-01 | 1995-10-05 | オーソ・フアーマシユーチカル・コーポレーシヨン | １−アリールスルホニル，アリールカルボニルおよび１−アリールホスホニル−３−フェニル−１，４，５，６−テトラヒドロピリダジン |
-
1997
- 1997-05-30 DE DE19723722A patent/DE19723722A1/de not_active Ceased
-
1998
- 1998-02-06 UA UA99127245A patent/UA64752C2/uk unknown
- 1998-05-29 HR HR980289A patent/HRP980289B1/xx not_active IP Right Cessation
- 1998-05-29 ZA ZA984655A patent/ZA984655B/xx unknown
- 1998-06-01 AR ARP980102552A patent/AR011480A1/es active IP Right Grant
- 1998-06-01 TW TW087108524A patent/TW577882B/zh not_active IP Right Cessation
- 1998-06-02 CN CNB98805597XA patent/CN100445272C/zh not_active Expired - Fee Related
- 1998-06-02 HU HU0002126A patent/HUP0002126A3/hu unknown
- 1998-06-02 EE EEP199900548A patent/EE04492B1/xx not_active IP Right Cessation
- 1998-06-02 AT AT98928338T patent/ATE286035T1/de not_active IP Right Cessation
- 1998-06-02 JP JP50026799A patent/JP2002502385A/ja not_active Ceased
- 1998-06-02 PT PT98928338T patent/PT986545E/pt unknown
- 1998-06-02 ES ES98928338T patent/ES2234121T3/es not_active Expired - Lifetime
- 1998-06-02 DE DE59812452T patent/DE59812452D1/de not_active Expired - Fee Related
- 1998-06-02 PL PL337088A patent/PL197887B1/pl unknown
- 1998-06-02 WO PCT/EP1998/003242 patent/WO1998054159A1/de not_active Ceased
- 1998-06-02 EA EA199900989A patent/EA004306B1/ru not_active IP Right Cessation
- 1998-06-02 ID IDW991498A patent/ID23499A/id unknown
- 1998-06-02 AU AU80211/98A patent/AU747083C/en not_active Ceased
- 1998-06-02 NZ NZ501359A patent/NZ501359A/en unknown
- 1998-06-02 BR BR9809703-2A patent/BR9809703A/pt not_active IP Right Cessation
- 1998-06-02 CA CA002305458A patent/CA2305458C/en not_active Expired - Fee Related
- 1998-06-02 TR TR1999/02924T patent/TR199902924T2/xx unknown
- 1998-06-02 CZ CZ0425799A patent/CZ296377B6/cs not_active IP Right Cessation
- 1998-06-02 EP EP98928338A patent/EP0986545B1/de not_active Expired - Lifetime
- 1998-06-02 IL IL13319598A patent/IL133195A0/xx active IP Right Grant
- 1998-06-02 KR KR10-1999-7011103A patent/KR100536870B1/ko not_active Expired - Fee Related
- 1998-06-02 SK SK1609-99A patent/SK284943B6/sk not_active IP Right Cessation
-
1999
- 1999-11-09 IS IS5241A patent/IS2498B/is unknown
- 1999-11-19 BG BG103903A patent/BG64212B1/bg unknown
- 1999-11-29 IL IL133195A patent/IL133195A/en not_active IP Right Cessation
- 1999-11-29 NO NO19995845A patent/NO325076B1/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU747083B2 (en) | Non-steroidal (hetero) cyclically substituted acylanilides with mixed gestagen and androgen activity | |
| US6245804B1 (en) | Nonsteroidal gestagens | |
| AU765159B2 (en) | Compounds and methods for modulation of estrogen receptors | |
| DK175824B1 (da) | Styrylpyrazoler,-isoxazoler og analoge forbindelser farmaceutiske præparater med aktivitet mod 5-lipoxygenase eller cyclooxygenase eller............ | |
| AU781282B2 (en) | Compounds and methods for modulation of estrogen receptors | |
| CZ20011866A3 (cs) | Nesteroidní antiflogistika | |
| JPH0753725B2 (ja) | ４ｈ―１―ベンゾピラン―４―オン誘導体およびその塩、それらの製造法並びにそれらを含有する抗炎症剤 | |
| KR101103118B1 (ko) | 신규한 1,3-디히드로-5-이소벤조퓨란카르보니트릴 유도체 화합물 및 이를 함유하는 조루증 치료용 약학조성물 | |
| CA2139307A1 (en) | 1-arylsulphonyl, arylcarbonyl and 1-arylphosphonyl-3-phenyl-1,4,5,6-tetrahydropyridazines | |
| HUT54617A (en) | Process for producing new substituted acyl-phenols and pharmaceutical compositions containing them | |
| JP2000502360A (ja) | スピロ環式ドーパミンレセプターサブタイプリガンド | |
| JPS6212214B2 (cg-RX-API-DMAC10.html) | ||
| Grover et al. | New Antifertility Agents. 2, 3-Diphenylbenzofurans1a | |
| JPS6025421B2 (ja) | 排卵抑制剤およびその製造方法 | |
| HU204520B (en) | Process for producing pharmaceutically active compounds and pharmaceutical compositions containing them | |
| US3678076A (en) | Tetrahydrodibenzothiophenes | |
| KR20080030622A (ko) | 비스테로이드성 프로게스테론 수용체 조절자 | |
| US3944570A (en) | 3,3-Disubstituted phthalides | |
| US3546252A (en) | Dimethyl oxa-steroids | |
| HK1029334A (en) | Non-steroidal (hetero) cyclically substituted acylanilides with mixed gestagen and androgen activity | |
| JPS5833872B2 (ja) | ヘキサヒドロジベンゾフラン −３− オンノシンキナユウドウタイオヨビ ソノエンルイノセイゾウホウ | |
| HUP0600651A2 (en) | 3,4-dihydrobenzo[1,2,3]thiadiazine-1,1-dioxide derivatives, process for their preparation, pharmaceutical compositions containing the same and their use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20090602 |