Retroviral protease inhibiting compounds

A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective combination of a compound of the formula:

• wherein R1 and R2 are independently selected from the group consisting of loweralkyl, cycloalkylalkyl and arylalkyl;
• R3 is loweralkyl, hydroxyalkyl or cycloalkylalkyl;
• R4 is aryl or heterocyclic;
• R5 is
• wherein n is 1, 2 or 3, m is 1, 2 or 3, m′ is 1 or 2, X is O, S or NH, Y is —CH2—, —O—, —S—or —N(R6)— wherein R6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y″ is —CH2— or —N(R6″)— wherein R6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y′ is —N(R6′)— wherein R6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, and Z is O, S or NH;
• and
• L1 is
• a) —O—,
• b) —S—,
• c) —N(R7)— wherein R7 is hydrogen, loweralkyl, cycloalkyl or cycloalkylalkyl,
• d) —O-alkylenyl-,
• e) —S—alkylenyl-,
• f) —S(O)-alkyleneyl-,
• g) —S(O)2-alkylenyl-,
• h) —N(R7)-alkylenyl- wherein R7 is defined as above,
• i) -alkylenyl-O—,
• j) -alkylenyl-S—,
• k) -alkylenyl-N(R7)— wherein R7 is defined as above,
• l) alkylenyl or
• m) alkenylenyl;
• or a pharmaceutically acceptable salt, ester or prodrug thereof, and another HIV protease inhibitor or a combination of other HIV protease inhibitors.

A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective combination of a compound of the formula:

• wherein R1 and R2 are independently selected from the group consisting of loweralkyl, cycloalkylalkyl and arylalkyl;
• R3 is loweralkyl, hydroxyalkyl or cycloalkylalkyl;
• R4 is aryl or heterocyclic;
• R5 is
• wherein n is 1, 2 or 3, m is 1, 2 or 3, m′ is 1 or 2, X is O, S or NH, Y is —CH2—, —O—, —S—or —N(R6)— wherein R6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y″ is —CH2— or —N(R6″)— wherein R6″ is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y′ is —N(R6″)— wherein R6″ is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, and Z is O, S or NH;
• and
• L1 is
• a) —O—,
• b) —S—,
• c) —N(R7)— wherein R7 is hydrogen, loweralkyl, cycloalkyl or cycloalkylalkyl,
• d) —O-alkylenyl-,
• e) —S-alkylenyl-,
• f) —S(O)-alkyleneyl-,
• g) —S(O)2-alkylenyl-,
• h) —N(R7)-alkylenyl- wherein R7 is defined as above,
• i) -alkylenyl-O—,
• j) -alkylenyl-S—,
• k) -alkylenyl-N(R7)— wherein R7 is defined as above,
• l) alkylenyl or
• m) alkenylenyl;
• or a pharmaceutically acceptable salt, ester or prodrug thereof, and another HIV protease inhibitor or a combination of other HIV protease inhibitors and a reverse transcriptase inhibitor or a combination of reverse transcriptase inhibitors.

A pharmaceutical composition comprising a pharmaceutical carrier and therapeutically effective combination of a compound of the formula:

• wherein R1 and R2 are independently selected from the group consisting of loweralkyl, cycloalkylalkyl and arylalkyl;
• R3 is loweralkyl, hydroxyalkyl or cycloalkylalkyl;
• R4 is aryl or heterocyclic;
• wherein n is 1, 2 or 3, m is 1, 2 or 3, m′ is 1 or 2, X is O, S or NH, Y is —CH2—, —O—, —S—or —N(R6)— wherein R6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y″ is —CH2— or —N(R6″)— wherein R6″ is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y′ is —N(R6′)— wherein R6′ is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, and Z is O, S or NH;
• and
• L1 is
• a) —O—,
• b) —S—,
• c) —N(R7)— wherein R7 is hydrogen, loweralkyl, cycloalkyl or cycloalkylalkyl,
• d) —O-alkylenyl-,
• e) —S-alkylenyl-,
• f) —S(O)-alkyleneyl-,
• g) —S(O)2-alkylenyl-,
• h) —N(R7)-alkylenyl- wherein R7 is defined as above,
• i) -alkylenyl-O—,
• j) -alkylenyl-S—,
• k) -alkylenyl-N(R7)— wherein R7 is defined as above,
• l) alkylenyl or
• m) alkenylenyl;
• or a pharmaceutically acceptable salt, ester or prodrug thereof, and another HIV protease inhibitor or a combination of other HIV protease inhibitors.

A pharmaceutical composition comprising a pharmaceutical carrier and therapeutically effective combination of a compound of the formula:

• wherein R1 and R2 are independently selected from the group consisting of loweralkyl, cycloalkylalkyl and arylalkyl;
• R3 is loweralkyl, hydroxyalkyl or cycloalkylalkyl;
• R4 is aryl or heterocyclic;
• R5 is
• wherein n is 1, 2 or 3, m is 1, 2 or 3, m′ is 1 or 2, X is O, S or NH, Y is —CH2—, —O—, —S—or —N(R6)— wherein R6 is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y″ is —CH2— or —N(R6″)— wherein R6″ is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, Y′ is —N(R6′)— wherein R6′ is hydrogen, loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, and Z is O, S or NH;
• and
• L1 is
• a) —O—,
• b) —S—, 1
• c) —N(R7)— wherein R7 is hydrogen, loweralkyl, cycloalkyl or cycloalkylalkyl,
• d) —O-alkylenyl-,
• e) —S-alkylenyl-,
• f) —S(O)-alkyleneyl-,
• g) —S(O) 2-alkylenyl-,
• h) —N(R7)-alkylenyl- wherein R7 is defined as above,
• i) -alkylenyl-O—,
• j) -alkylenyl—S—,
• k) -alkylenyl-N(R7)— wherein R7 is defined as above,
• l) alkylenyl or
• m) alkenylenyl;
• or a pharmaceutically acceptable salt, ester or prodrug thereof, and a reverse transcriptase inhibitor or a combination of reverse transcriptase inhibitors.