Nonpeptide HIV-1 protease inhibitors
Novel compounds and compositions for treating patients in need of relief from HIV, AIDS and AIDS-related diseases are described. Methods for treating HIV, AIDS, and AIDS-related diseases using the compounds described herein are also described.
1. A compound of the formula
or a pharmaceutically acceptable salt thereof; wherein
R is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted;
X 2 and X 3 are —C(O)—;
Q 1 is optionally substituted 1,3-phenylene;
R 1A and X 1A together with the attached nitrogen form an optionally substituted heterocycle or R, R 1A and X 1A and the attached nitrogen are taken together to form an optionally substituted heterocycle;
X 4 is —C(O)— or —S(O) 2 —;
R 3 is alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted;
X 5 is optionally substituted alkylene;
R 2 is selected from the group consisting of hydrogen, —S(O) 2 R 14 , —C(O)R 12 , —N(R 8 )R 9 , alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;
R 4 and R 5 are each independently selected from the group consisting of hydrogen, halogen, —OH, —NO 2 , —N(R 8 )R 9 , —OR 10 , —S(O) n R 11 , —C(O)R 12 , alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, each of which is optionally substituted;
n and q are each independently 0, 1, or 2 in each instance;
R 20 is hydrogen;
R 8 is in each instance independently selected from the group consisting of hydrogen, —C(O)R 13 , —S(O) 2 R 14 , alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;
R 9 is in each instance independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;
R 10 is in each instance independently selected from the group consisting of —C(O)R 13 , alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;
R 11 is in each instance independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, hetoercycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted, when n is 0; R 11 is in each instance independently selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted, when n is 1; and R 11 is in each instance independently selected from the group consisting of —N(R 15 )R 16 , alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted, when n is 2;
R 12 and R 13 are each independently selected from the group consisting of hydrogen, —OR 19 , —N(R 18 )R 19 , alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted;
R 14 is in each instance independently selected from the group consisting of hydrogen, N(R 18 )R 19 , alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted; and
R 15 , R 16 , R 17 , R 18 , and R 19 are in each instance independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, heterocycloalkyl, heterocycloalkyl-alkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which is optionally substituted.
2. The compound of claim 1 , wherein R 1A and X 1A together with the attached nitrogen form an optionally substituted heterocycle.
3. The compound of claim 1 , wherein R 3 is C 3 -C 10 alkyl or cycloalkyl.
4. The compound of claim 1 , wherein R is an optionally substituted heteroaryl.
5. The compound of claim 1 , wherein R 5 is optionally substituted aryl.
6. The compound of claim 1 wherein X 4 is SO 2 ; and R 4 is optionally substituted aryl.
7. The compound of claim 1 , wherein R 3 is branched alkyl.
8. The compound of claim 1 , wherein X 5 is optionally substituted alkylene; and R 5 is optionally substituted aryl.
9. The compound of claim 1 wherein R, R 1A and X 1A and the attached nitrogen are taken together to form an optionally substituted heterocycle.
10. A pharmaceutical composition comprising a compound of claim 1 ; and one or more pharmaceutically acceptable carriers, diluents, or excipients, or a combination thereof.
11. The compound of claim 1 , which is:
or a pharmaceutically acceptable salt thereof.