US4386080A
Expired / Lapsed
US
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Anti-androgenic amide derivative
Assignee: Imperial Chemical Industries Ltd
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Filing: 1981-05-21
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Granted: 1983-05-31
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Expires: 2001-05-21
Abstract
Abstract Novel 3,4-disubstituted-N-acylanilines of the formula: <IMAGE> wherein R1, R2 and ring A are defined in claim 1; wherein R3 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R5 as stated below; wherein R4 is alkyl of 2 to 4 carbon atoms, or has the formula -CX1X2X3 wherein X1, X2 and X3, which may be the same or different, each is hydrogen, fluorine or chlorine; wherein R5 is hydrogen, hydroxy or alkoxy or acyloxy each of up to 15 carbon atoms, or is joined to R3 to form an oxycarbonyl group such that together with the <IMAGE> part of the molecule it forms an oxazolidinedione group; and wherein R6 is hydrogen or halogen. These compounds possess antiandrogenic activity and are useful for the treatment of androgen dependent or prostatic diseases. Representative of the compounds is 3,4-dichloro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline. Also disclosed are processes for the manufacture of the compounds and pharmaceutical and veterinary compositions containing them.
Inventors
- 👤 Neville S. Crossley
- 👤 Alasdair T. Glen
- 👤 Leslie R. Hughes
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 14:08
CPC Classifications
C; C07; C07D; C07D263/00; C07D263/02; C07D263/30; C07D263/34; C07D263/44; C07C; C07C205/00; C07C205/49; C07C205/56; C07C255/00; C07C323/00; C07C59/00; C07C59/40; C07C59/42; C07C59/56; C07D303/00; C07D303/02; C07D303/48
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
237 words
An acylanilide of the formula: ##STR16## wherein R 1 is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo or hydrogen, or alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo or iodo, or alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R 5 as stated below; wherein R 4 is alkyl of 2 to 4 carbon atoms, or has the formula --CX 1 X 2 X 3 wherein X 1 , X 2 and X 3 , which may be the same or different, each is hydrogen, fluorine or chlorine; wherein R 5 is hydrogen, hydroxy or alkoxy or acyloxy each of up to 15 carbon atoms, or is joined to R 3 to form an oxycarbonyl group such that together with the ##STR17## part of the molecule it forms an oxazolidinedione group; wherein R 6 is hydrogen or halogen; and wherein the benzene ring A bears one, two or three substituents selected from halogen, nitro, carboxy, carbamoyl and cyano, and alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenylthio, phenylsulphinyl and phenylsulphonyl.
Claim 2
Dependent Claim
237 words
An acylanilide of the formula: ##STR16## wherein R 1 is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo or hydrogen, or alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo or iodo, or alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R 5 as stated below; wherein R 4 is alkyl of 2 to 4 carbon atoms, or has the formula --CX 1 X 2 X 3 wherein X 1 , X 2 and X 3 , which may be the same or different, each is hydrogen, fluorine or chlorine; wherein R 5 is hydrogen, hydroxy or alkoxy or acyloxy each of up to 15 carbon atoms, or is joined to R 3 to form an oxycarbonyl group such that together with the ##STR17## part of the molecule it forms an oxazolidinedione group; wherein R 6 is hydrogen or halogen; and wherein the benzene ring A bears one, two or three substituents selected from halogen, nitro, carboxy, carbamoyl and cyano, and alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenylthio, phenylsulphinyl and phenylsulphonyl.
Claim 3
Dependent Claim
173 words
An acylanilide as claimed in claim 1 wherein R 1 is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo, hydrogen, methyl, ethyl, methoxy, ethoxy, formyl, acetyl, methylthio, ethylthio, methylsulphinyl, methylsulphonyl, trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo, formyl, acetyl, methylthio, ethylthio, methylsulphinyl, methylsulphonyl, trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen, methyl or ethyl, or is joined to R 5 as stated below; wherein R 4 is methyl, ethyl, n-propyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl or trichloromethyl; wherein R 5 is hydrogen, hydroxy, methoxy, ethoxy, propyloxy, n-butyloxy, decyloxy, acetoxy, propionyloxy, decanoyloxy or dodecanoyloxy, or is joined to R 3 to form an oxycarbonyl group as stated in claim 1; wherein R 6 is hydrogen or chloro; and wherein the benzene ring A bears one or two substituents selected from fluoro, chloro, bromo, iodo, nitro, carboxy, carbamoyl, cyano, formyl, acetyl, methylthio, ethylthio, methylsulphinyl, methylsulphonyl, trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N-methylcarbamoyl, phenylthio, phenylsulphinyl and phenylsulphonyl.
Claim 4
Dependent Claim
139 words
An acylanilide as claimed in claim 1 wherein R 1 is trifluoromethyl and R 2 is nitro or cyano; or R 1 is chloro and R 2 is chloro, nitro, cyano, methylthio, methylsulphinyl or methylsulphonyl; or R 1 is cyano and R 2 chloro; or R 1 is nitro and R 2 is chloro or cyano; or R 1 is methylthio and R 2 is cyano; or R 1 is hydrogen and R 2 is methylthio; wherein R 3 is hydrogen; wherein R 4 is methyl; wherein R 5 is hydroxy; wherein R 6 is hydrogen; and wherein the benzene ring A bears one or two substituents only, one of which is a nitro, fluoro, chloro, trifluoromethyl, cyano, methoxycarbonyl, methylthio, methylsulphinyl or methanesulphonyl substituent in the para-position and the other of which, if present, is chloro in the meta-position.
Claim 5
Dependent Claim
66 words
An acylanilide as claimed in claim 1 wherein R 1 and R 2 , which may be the same or different, each is cyano, nitro, trifluoromethyl or chloro, R 3 and R 6 are both hydrogen, R 4 is methyl, R 5 is hydroxy and the ring A bears one substituent in the para-position which is a nitro, fluoro, trifluoromethyl, cyano, methoxycarbonyl, methylthio or methylsulphinyl substituent.
Claim 6
Dependent Claim
6 words
The compound 3,4-dichloro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline or 4-cyano-3-trifluoromethyl-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline.
Claim 7
Dependent Claim
6 words
The compound 3,4-dichloro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline or 4-cyano-3-trifluoromethyl-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline.
Claim 8
Dependent Claim
12 words
The compound 3-chloro-4-nitro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 3-chloro-4-methylsulphonyl-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-trifluoromethylphenylpropionyl)aniline; 3-chloro-4-nitro-N-(2-hydroxy-2-p-trifluoromethylphenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-p-cyanophenyl-2-hydroxypropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-p-fluorophenyl-2-hydroxypropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-methylsulphinylphenylpropionyl)aniline; 3,4-dichloro-N-(2-hydroxy-2-p-methylsulphinylphenylpropionyl)aniline; and 3,4-dichloro-N-(2-p-acetylphenyl-2-hydroxypropionyl)aniline.
Claim 9
Dependent Claim
12 words
The compound 3-chloro-4-nitro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 3-chloro-4-methylsulphonyl-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-trifluoromethylphenylpropionyl)aniline; 3-chloro-4-nitro-N-(2-hydroxy-2-p-trifluoromethylphenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-p-cyanophenyl-2-hydroxypropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-p-fluorophenyl-2-hydroxypropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-methylsulphinylphenylpropionyl)aniline; 3,4-dichloro-N-(2-hydroxy-2-p-methylsulphinylphenylpropionyl)aniline; and 3,4-dichloro-N-(2-p-acetylphenyl-2-hydroxypropionyl)aniline.
Claim 10
Dependent Claim
31 words
A pharmaceutical or veterinary composition which comprises an effective anti-androgenic amount of an acylanilide, claimed in any of claims 1 to 6, in association with a pharmaceutically acceptable diluent or carrier.
Claim 11
Dependent Claim
28 words
A composition as claimed in claim 7 which additionally contains one or more drugs selected from antioestrogens, progestins, inhibitors or gonadotrophin secretion, cytotoxic agents, antibiotics and antiinflammatory agents.
Claim 12
Independent Claim
37 words
A method of producing an antiandrogenic effect in a warm-blooded animal in need of such an effect which comprises administering to said animal an effective amount of an acylanilide claimed in any of claims 1 to 6.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-05-30 | 1986-11-29 | 1987-05-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-05-30 | 1990-11-29 | 1991-05-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-05-30 | 1994-11-29 | 1995-05-31 | $7700.00 | Window Closed / Lapsed |