Details for Patent: 7,968,707
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Title: | Retroviral protease inhibiting compounds |
Abstract: | A compound of the formula: ##STR00001## is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed. |
Inventor(s): | Sham; Hing Leung (Mundelein, IL), Norbeck; Daniel W. (Crystal Lake, IL), Chen; Xiaoqi (Libertyville, IL), Betebenner; David A. (Gurnee, IL), Kempf; Dale J. (Libertyville, IL), Herrin; Thomas R. (Waukegan, IL), Kumar; Gondi N. (Round Lake Beach, IL), Condon; Stephen L. (Kenosha, WI), Cooper; Arthur J. (Lake Villa, IL), Dickman; Daniel A. (Grayslake, IL), Hannick; Steven M. (Highland Park, IL), Kolaczkowski; Lawrence (Gurnee, IL), Oliver; Patricia A. (Lindenhurst, IL), Plata; Daniel J. (Wads Worth, IL), Stengel; Peter J. (Waukegan, IL), Stoner; Eric J. (Kenosha, WI), Tien; Jieh-Heh J. (Libertyville, IL), Liu; Jih-Hua (Greek Oaks, IL), Patel; Ketan M. (Arlington Heights, IL) |
Assignee: | Abbott Laboratories (Abbott Park, IL) |
Filing Date: | Feb 27, 2007 |
Application Number: | 11/679,227 |
Claims: | 1. A process for the preparation of a compound of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof, ##STR00088## said process comprising reacting a compound of the formula: ##STR00089## with a compound of the formula: ##STR00090## or a salt or activated ester derivative thereof, wherein: R.sub.1 and R.sub.2 are independently selected from the group consisting of loweralkyl, cycloalkylalkyl and arylalkyl; R.sub.3 is loweralkyl, hydroxyalkyl or cycloalkylalkyl; R.sub.4 is aryl; R.sub.5 is ##STR00091## wherein n is 1, 2 or 3, X is O, S or NH, and Y is --O-- or --N(R.sub.6)-- wherein R.sub.6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl; and L.sub.1 is selected from the group consisting of: a) --O--, b) --S--, c) --N(R.sub.7)-- wherein R.sub.7 is hydrogen loweralkyl, cycloalkyl or cycloalkylalkyl, d) --O-alkylenyl-, e) --S-alkylenyl-, f) --S(O)-alkylenyl-, g) --S(O).sub.2-alkylenyl-, h) --N(R.sub.7)-akylenyl- wherein R.sub.7 is defined as above, i) -alkylenyl-O--, j) -alkylenyl-S--, k) -alkylenyl-N(R.sub.7)-- wherein R.sub.7 is defined as above, l) -alkylenyl-, and m) -alkenylenyl-. 2. The process of claim 1, wherein R.sub.1 and R.sub.2 are arylalkyl, R.sub.3 is loweralkyl, R.sub.4 is aryl, and L.sub.1 is --O-alkylenyl-. 3. The process of claim 1, wherein R.sub.1 and R.sub.2 are benzyl or R.sub.1 is benzyl and R.sub.2 is isopropyl, R.sub.3 is loweralkyl, R.sub.4 is 2,6-dimethylphenyl which is optionally substituted with a substituent selected from the group consisting of loweratkyl and halo, L.sub.1 is --O--CH.sub.2--, n is 1 or 2, X is O or S, and Y is --CH.sub.2-- or --NH--. 4. The process of claim 1, wherein R.sub.1 and R.sub.2 are benzyl, R.sub.3 is loweralkyl, R.sub.4 is 2,6-dimethylphenyl, L.sub.1 is --O--CH.sub.2--, n is 1 or 2, X is O or S, and Y is --NH--. 5. A process for the preparation of a compound of formula I or a pharmaceutically acceptable salt, ester or prodrug thereof, ##STR00092## said process comprising reacting compound of the formula: ##STR00093## with a compound of the formula: ##STR00094## or an activated ester derivative thereof, wherein: R.sub.1 and R.sub.2 are independently selected from the group consisting of loweralkyl, cycloalkylalkyl and arylalkyl; R.sub.3 is loweralkyl, hydroxyalkyl or cycloalkylalkyl; R.sub.4 is aryl; R.sub.5 is ##STR00095## wherein n is 1, 2 or 3, X is O, S or NH, and Y is --O-- or --N(R.sub.6)-- wherein R.sub.6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl; and L.sub.1 is selected from the group consisting of: a) --O--, b) --S--, c) --N(R.sub.7)-- wherein R.sub.7 is hydrogen, loweralkyl, cycloalkyl or cyoloalkylalkyl, d) --O-alkylenyl-, e) --S-alkylenyl-, f) --S(O)-alkylenyl-, g) --S(O).sub.2-alkylenyl-, h) --N(R.sub.7)-alkylenyl- wherein R.sub.7 is defined as above, i) -alkylenyl-O--, j) -alkylenyl-S--, k) -alkylenyl-N(R.sub.7)-- wherein R.sub.7 is defined as above, l) -alkylenyl-, and m) -alkenylenyl-. 6. The process of claim 5, wherein R.sub.1 and R.sub.2 are arylalkyl, R.sub.3 is loweralkyl, R.sub.4 is aryl, and L.sub.1 is --O-alkylenyl-. 7. The process of claim 5, wherein R.sub.1 and R.sub.2 are benzyl or R.sub.1 is benzyl and R.sub.2 is isopropyl, R.sub.3 is loweralkyl, R.sub.4 is 2,6-dimethylphenyl which is optionally substituted with a substituent selected from the group consisting of loweralkyl and halo, L.sub.1 is --O--CH.sub.2--, n is 1 or 2, X is O or S, and Y is --CH.sub.2-- or --NH--. 8. The process of claim 5, wherein R.sub.1 and R.sub.2 are benzyl, R.sub.3 is loweralkyl, R.sub.4 is 2,6-dimethylphenyl, L.sub.1 is --O--CH.sub.2--, n is 1 or 2, X is O or S, and Y --NH--. 9. A process for the preparation of a compound of Formula I according to claim 4, wherein said compound is (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-[2S-(1-tetrahyd- ro-pyrimid-2-onyl)-3-methyl butanoyl]amino-1,6-diphenylhexane, and said process further comprises: dissolving said compound in ethanol, isopropanol, or acetonitrile to provide a solution, and adding water to said solution to produce an amorphous solid. 10. A process for the preparation of a compound of Formula I according to claim 8, wherein said compound is (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-[2S-(1-tetrahyd- ro-pyrimid-2-onyl)-3-methyl butanoyl]amino-1,6-diphenylhexane, and said process further comprises: dissolving said compound in ethanol, isopropanol, or acetonitrile to provide a solution, and adding water to said solution to produce an amorphous solid. 11. A process for the preparation of a compound of Formula I according to claim 4, wherein X is O. 12. A process for the preparation of a compound of Formula I according to claim 8, wherein X is O. |