Antiviral agent
The present invention provides an integrase inhibitor. The inventors have found the following compound of formula (I) possessing an integrase inhibitory activity. (wherein, R C and R D taken together with the neighboring carbon atoms form a ring which may be a condensed ring, Y is hydroxyl, mercapto or amino; Z is O, S or NH; R A is a group shown by (wherein, C ring is N-containing aromatic heterocycle) or the like).
1. A method of inhibiting HIV integrase activity, the method comprising contacting an HIV integrase protein with an effective amount of a compound of Formula (I-z):
wherein
R C and R D taken together with the neighboring carbon atoms form a 5- to 6-membered heterocycle which contains heteroatom(s) of O and/or N and which is optionally condensed with a benzene ring;
R B is 2-furyl; and
the ring formed by R C and R D and the neighboring carbon atoms is optionally substituted with —Z 1 —Z 2 —Z 3 —R 1 and/or C 1 -C 6 alkyl, wherein
Z 1 and Z 3 are independently a bond or C 1 -C 6 alkylene;
Z 2 is a bond, —NR 2 SO 2 —, —NR 2 CO—, or —CONR 2 ;
R 2 is hydrogen; and
R 1 is aryl or heteroaryl, each of which is optionally substituted with C 1 -C 6 alkyl;
or a salt thereof.
2. The method of claim 1 , wherein R C and R D taken together with the neighboring carbon atoms form a 6-membered N-containing heterocycle.
3. The method of claim 1 , wherein the ring formed by R C and R D is substituted with C 1 -C 6 alkyl.
4. The method of claim 1 , wherein the ring formed by R C and R D is substituted with —Z 1 —Z 2 —Z 3 —R 1 , wherein
Z 1 is C 1 -C 6 alkylene;
Z 2 is —NR 2 CO—;
Z 3 is a bond;
R 2 is hydrogen; and
R 1 is heteroaryl optionally substituted with C 1 -C 6 alkyl.
5. The method of claim 2 , wherein the ring formed by R C and R D and the neighboring carbon atoms is substituted with C 1 -C 6 alkyl.
6. The method of claim 1 , wherein the ring formed by R C and R D and the neighboring carbon atoms is substituted with —Z 1 —Z 2 —Z 3 —R 1 , wherein
Z 1 and Z 3 are independently a bond or C 1 -C 6 alkylene;
Z 2 is a bond, —NR 2 SO 2 —, —NR 2 CO—, or —CONR 2 ;
R 2 is hydrogen; and
R 1 is aryl or heteroaryl, each of which is optionally substituted with C 1 -C 6 alkyl.
7. The method of claim 2 , wherein the ring formed by R C and R D and the neighboring carbon atoms is substituted with methyl.
8. The method of claim 7 , wherein the ring formed by R C and R D and the neighboring carbon atoms is substituted with —Z 1 —Z 2 —Z 3 —R 1 , wherein
Z 1 is C 1 -C 6 alkylene;
Z 2 is a bond, —NR 2 SO 2 —, —NR 2 CO—, or —CONR 2 —;
Z 3 is a bond;
R 2 is hydrogen; and
R 1 is aryl or heteroaryl, each of which is optionally substituted with C 1 -C 6 alkyl.
9. The method of claim 8 , wherein
Z 2 is —NR 2 CO—; and
R 1 is heteroaryl, which is optionally substituted with C 1 -C 6 alkyl.
10. The method of claim 9 , wherein R 1 is 1,3,4-oxadiazol-2-yl optionally substituted with C 1 -C 6 alkyl.
11. The method of claim 10 , wherein R 1 is 1,3,4-oxadiazol-2-yl substituted with C 1 -C 6 alkyl.