Claims
- 1. A compound of formula I ##STR24## wherein: R.sup.0 is hydrogen, C.sub.1 -C.sub.6 alkoxycarbonyl, or C.sub.2 -C.sub.6 alkanoyl;
- n is 0, 1 or 2;
- R is phenyl, naphthyl or indolyl;
- R.sup.1 is phenyl, naphthyl or --S-R.sup.1x, where R.sup.1x is phenyl or naphthyl;
- R.sup.2 is --CH(CH.sub.3).sub.2, --CH.sub.2 C(O)NH.sub.2, CH.sub.2 -imidazolyl, cyano (C.sub.1 -C.sub.4)-alkyl, --CH.sub.2 SCH.sub.3 or --CH.sub.2 C(O)-R.sup.2a, where
- R.sup.2a is C.sub.1 -C.sub.4 alkylamino;
- X is a group having the structure: ##STR25## Y is phenyl or naphthyl; R.sup.3a is a group having the structure:
- --C(O)-NR.sup.4 R.sup.4 ;
- R.sup.4 at each occurrence is independently hydrogen, C.sub.1 -C.sub.6 alkyl or hydroxy (C.sub.1 -C.sub.4 ) alkyl;
- or a pharmaceutically acceptable salt thereof.
- 2. A compound according to claim 1 of the formula: ##STR26## wherein: R.sup.0 is hydrogen or C.sub.1 -C.sub.4 alkoxycarbonyl;
- R.sup.2 is --CH(CH.sub.3).sub.2, --CH.sub.2 -C(O)NH.sub.2 or --CH.sub.2 -imidazol-4-yl; and
- R.sup.3a is --C(O)NH(t-butyl);
- or a pharmaceutically acceptable salt thereof.
- 3. A compound according to claim 2 wherein:
- R.sup.0 is t-butoxycarbonyl;
- R is naphth-1-yl, phenyl or indol-3-yl;
- R.sup.2 is --CH.sub.2 -C(O)NH.sub.2 ;
- R.sup.1 is phenyl; and
- Y is phenyl;
- or a pharmaceutically acceptable salt thereof.
- 4. A compound according to claim 3 that is 2R- (2R*, 3S*, 6S*, 9S*)!-N-t-butyl-2- 2 -hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(1-methylethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 5. A compound according to claim 3 that is 2R- (2R*, 3S*, 6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(1-methylethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 6. A compound according to claim 3 that is 2R-(2R*,3S*,6S*,9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 7. A compound according to claim 3 that is 2R-(2R*,3S*,6S*,9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-phenyl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 8. A compound according to claim 3 that is 2R-(2R*,3S*,6S*,9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(imidazol-4-ylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 9. A compound according to claim 3 that is 2R-(2R*,3S*,6S*,9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-indol-3-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 10. A compound according to claim 3 that is 2R-(2R*,3S*,6S*,9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-indol-3-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 11. A compound according to claim 3 that is 2R-(2R*, 3S*, 6S*, 9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 12. A pharmaceutical formulation comprising one or more pharmaceutically acceptable carriers, diluents or excipients and a compound of claim 1.
- 13. A pharmaceutical formulation according to claim 12 where the compound is one of the formula: ##STR27## wherein: R.sup.0 is hydrogen or C.sub.1 -C.sub.4 alkoxycarbonyl;
- R.sup.2 is --CH(CH.sub.3).sub.2, --CH.sub.2 -C(O)NH.sub.2 or --CH.sub.2 -imidazol-4-yl; and
- R.sup.3a is --C(O)NH(t-butyl);
- or a pharmaceutically acceptable salt thereof.
- 14. A pharmaceutical formulation according to claim 13 where the compound is one wherein:
- R.sup.0 is t-butoxycarbonyl;
- R is naphth-1-yl, phenyl or indol-3-yl;
- R.sup.2 is --CH.sub.2 -C(O)NH.sub.2 ;
- R.sup.1 is phenyl; and
- Y is phenyl;
- or a pharmaceutically acceptable salt thereof.
- 15. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*,3S*,6S*,9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(1-methylethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 16. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*,3S*, 6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(1-methylethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 17. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*,3S*, 6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 18. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*,3S*,6S*,9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10phenyl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 19. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*,3S*,6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(imidazol-4-ylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 20. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*,3S*,6S*,9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-indol-3yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 21. A pharmaceutical formulation according to claim 14 where the compound is 2R-(2R*, 3S*, 6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-indol-3-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 22. A method of inhibiting HIV replication comprising administering to an HIV infected cell, a cell susceptible to HIV infection or a primate in need thereof an effective amount of a compound of claim 1.
- 23. A method according to claim 22 where the compound is one of the formula: ##STR28## wherein: R.sup.0 is hydrogen or C.sub.1 -C.sub.4 alkoxycarbonyl;
- R.sup.2 is --CH(CH.sub.3).sub.2, --CH.sub.2 -C(O)NH.sub.2 or --CH.sub.2 -imidazol-4-yl; and
- R.sup.3a is --C(O)NH(t-butyl);
- or a pharmaceutically acceptable salt thereof.
- 24. A method according to claim 23 where the compound is one wherein:
- R.sup.0 is t-butoxycarbonyl;
- R is naphth-1-yl, phenyl or indol-3-yl;
- R.sup.2 is --CH.sub.2 -C(O)NH.sub.2 ;
- R.sup.1 is phenyl; and
- Y is phenyl;
- or a pharmaceutically acceptable salt thereof.
- 25. A method according to claim 24 where the compound is 2R- (2R*, 3S*, 6S*, 9S*)!-N-t-butyl-2- 2 -hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(1-methylethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 26. A method according to claim 24 where the compound is 2R-(2R*, 3S*, 6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(1-methylethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 27. A method according to claim 24 where the compound is 2R-(2R*,3S*,6S*,9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza -5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 28. A method according to claim 24 where the compound is 2R-(2R*, 3S*, 6S*, 9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-3-phenylmethyl-4,7-N(t-butoxycarbonyl)amino-10-phenyl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 29. A method according to claim 24 where the compound is 2R-(2R*, 3S*, 6S*, 9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(imidazol-1-ylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 30. A method according to claim 24 where the compound is 2R-(2R*, 3S*, 6S*, 9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-indol-3-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 31. A method according to claim 24 where the compound is 2R-(2R*,3S*,6S*,9R*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-indol-3-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
- 32. A method according to claim 24 where the compound is 2R-(2R*,3S*,6S*,9S*)!-N-t-butyl-2- 2-hydroxy-3-phenylmethyl-4,7-diaza-5,8-dioxo-6-(carbamoylmethyl)-9-N(t-butoxycarbonyl)amino-10-naphth-1-yl!decyl benzamide; or a pharmaceutically acceptable salt thereof.
Parent Case Info
This application is a continuation-in-part continuation of application Ser. No. 07/995,282, filed on Dec. 22, 1992, now abandoned.
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Continuations (1)
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Number |
Date |
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Parent |
995282 |
Dec 1992 |
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