US5663169A
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US
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Benzoxazinones as inhibitors of HIV reverse transcriptase
Assignee: Merck Sharp & Dohme LLC
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Filing: 1995-06-02
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Granted: 1997-09-02
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Expires: 2015-06-02
Abstract
Abstract Certain benzoxazinones are useful in the inhibition of HIV reverse transcriptase (including its resistant varieties), the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable saks, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.
Inventors
- 👤 Steven D. Young
- 👤 Linda S. Payne
- 👤 Susan F. Britcher
- 👤 Lekhanh O. Tran
- 👤 William C. Lumma, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 13:33
CPC Classifications
C; C07; C07D; C07D265/00; C07D265/04; C07D265/12; C07D265/14; C07D265/18; A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/535; A61K31/536; A61K31/70; A61K45/00; A61K45/06
Claims Analysis
Total Claims: 8
Claim 1
Independent Claim
282 words
A method of inhibiting HIV reverse transcriptase comprising administering to a mammal a pharmaceutically acceptable carrier and an effective amount of a compound of Formula I: ##STR82## or pharmaceutically acceptable salt thereof, wherein: X is halo, X 1 is trihalomethyl, or pentahaloethyl; Z is O; R is: (a) C 1-8 alkyl, unsubsdtuted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino- C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A, or a compound of Formula II: ##STR83## or pharmaceutically acceptable salt thereof, wherein: X is halo; X 1 is trihalomethyl; pentahaloethyl; C 2-5 alkyl; C 2-5 alkynyl; C 3-5 cycloalkyl; or aryl; Z is O or S; and R is: (a) C 1-8 alkyl, unsubstituted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino-C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A.
Claim 2
Independent Claim
282 words
A method of inhibiting HIV reverse transcriptase comprising administering to a mammal a pharmaceutically acceptable carrier and an effective amount of a compound of Formula I: ##STR82## or pharmaceutically acceptable salt thereof, wherein: X is halo, X 1 is trihalomethyl, or pentahaloethyl; Z is O; R is: (a) C 1-8 alkyl, unsubsdtuted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino- C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A, or a compound of Formula II: ##STR83## or pharmaceutically acceptable salt thereof, wherein: X is halo; X 1 is trihalomethyl; pentahaloethyl; C 2-5 alkyl; C 2-5 alkynyl; C 3-5 cycloalkyl; or aryl; Z is O or S; and R is: (a) C 1-8 alkyl, unsubstituted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino-C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A.
Claim 3
Independent Claim
44 words
A method of inhibiting HIV reverse transcriptase comprising administering to a mammal a pharmaceutically acceptable carrier and an effective amount of a compound selected from the group consisting of: (-) 6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (-) 6-chloro-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-) 6-chloro-4-(2-cyanophenyl)ethynyl-4-(1,1,1-trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-)4-(1-chloro-1,1-difluoromethyl)-4-(2-phenylethynyl)-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or (+/-)4-(2-[dimethylaminomethyl]ethynyl)-4-trifluoromethyl-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or a pharmaceutically acceptable saIt thereof.
Claim 4
Independent Claim
44 words
A method of inhibiting HIV reverse transcriptase comprising administering to a mammal a pharmaceutically acceptable carrier and an effective amount of a compound selected from the group consisting of: (-) 6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (-) 6-chloro-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-) 6-chloro-4-(2-cyanophenyl)ethynyl-4-(1,1,1-trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-)4-(1-chloro-1,1-difluoromethyl)-4-(2-phenylethynyl)-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or (+/-)4-(2-[dimethylaminomethyl]ethynyl)-4-trifluoromethyl-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or a pharmaceutically acceptable saIt thereof.
Claim 5
Independent Claim
293 words
A method of preventing infection of HIV, or of treating infection by HIV or of treating AIDS or ARC comprising administering to a mammal a pharmaceutically acceptable carder and an effective mount of a compound of Formula I: ##STR84## or pharmaceutically acceptable salt thereof, wherein: X is halo, X 1 is trihalomethyl, or pentahaloethyl; Z is O; R is: (a) C 1-8 alkyl, unsubstituted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino- C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstimted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstimted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstimted or substituted with A, or a compound of Formula II: ##STR85## or pharmaceutically acceptable salt thereof, wherein: X is halo; X 1 is trihalomethyl; pentahaloethyl; C 2-5 alkyl; C 2-5 alkynyl; C 3-5 cycloalkyl; or aryl; Z is O or S; R is: (a) C 1-8 alkyl, unsubstimted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino-C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstimted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with i) A, or (ii) aryl, unsubstituted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A.
Claim 6
Independent Claim
293 words
A method of preventing infection of HIV, or of treating infection by HIV or of treating AIDS or ARC comprising administering to a mammal a pharmaceutically acceptable carder and an effective mount of a compound of Formula I: ##STR84## or pharmaceutically acceptable salt thereof, wherein: X is halo, X 1 is trihalomethyl, or pentahaloethyl; Z is O; R is: (a) C 1-8 alkyl, unsubstituted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino- C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstimted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstimted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstimted or substituted with A, or a compound of Formula II: ##STR85## or pharmaceutically acceptable salt thereof, wherein: X is halo; X 1 is trihalomethyl; pentahaloethyl; C 2-5 alkyl; C 2-5 alkynyl; C 3-5 cycloalkyl; or aryl; Z is O or S; R is: (a) C 1-8 alkyl, unsubstimted or substituted with A, and A is halo, C 3-6 cycloalkyl, CN, hydroxy, C 1-4 alkoxy, C 2-4 alkynyl-C 1-4 alkoxy, aryloxy, C 1-4 alkylcarbonyl, nitro, di(C 1-2 alkyl)amino, C 1-4 alkylamino-C 1-2 alkyl, heterocycle, or arylthio; (b) C 2-4 alkenyl, unsubstimted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A; (c) C 2-5 alkynyl, unsubstituted or substituted with i) A, or (ii) aryl, unsubstituted or substituted with A; or (d) C 3-4 cycloalkyl, unsubstituted or substituted with (i) A, or (ii) aryl, unsubstituted or substituted with A.
Claim 7
Independent Claim
58 words
A method of preventing infection of HIV, or of treating infection by HIV or of treating AIDS or ARC, comprising administering to a mammal a pharmaceutically acceptable carder and an effective amount of a compound selected from the group consisting of: (-) 6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (-) 6-chloro-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-) 6-chloro-4-(2-cyanophenyl)ethynyl-4-(1,1,1-trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-) 4-(1-chloro-1,1-difluoromethyl)-4-(2-phenylethynyl)-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or (+/-) 4-(2-[dimethylaminomethyl]ethynyl)-4-trifluoromethyl-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or a pharmaceutically acceptable salt thereof.
Claim 8
Independent Claim
58 words
A method of preventing infection of HIV, or of treating infection by HIV or of treating AIDS or ARC, comprising administering to a mammal a pharmaceutically acceptable carder and an effective amount of a compound selected from the group consisting of: (-) 6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (-) 6-chloro-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-) 6-chloro-4-(2-cyanophenyl)ethynyl-4-(1,1,1-trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, (+/-) 4-(1-chloro-1,1-difluoromethyl)-4-(2-phenylethynyl)-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or (+/-) 4-(2-[dimethylaminomethyl]ethynyl)-4-trifluoromethyl-6-chloro-1,4-dihydro-2H-3,1-benzoxazin-2-one, or a pharmaceutically acceptable salt thereof.
References Cited (Backward Citations)
GB1135899A
Cited
US3526621A
Cited
US3682933A
Cited
US4313873A
Cited
EP0093922A2
Cited
US4857511A
Cited
EP0384552A2
Cited
EP0394553A2
Cited
WO1991009849A1
Cited
WO1991018591A1
Cited
WO1992000979A1
Cited
WO1992004328A1
Cited
EP0491218A1
Cited
WO1992016508A1
Cited
US5179093A
Cited
US5434152A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-09-01 | 2001-03-03 | 2001-09-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-09-01 | 2005-03-03 | 2005-09-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-09-01 | 2009-03-03 | 2009-09-02 | $7700.00 | Window Closed / Lapsed |