4-oxoquinoline compound and use thereof as pharmaceutical agent
An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.
1. A method for the treatment of an HIV infection comprising:
administering to a mammal in need thereof a therapeutically effective amount of a compound of formula [I], or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof:
wherein,
ring Cy is a C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the following group A or a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group A,
wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom, and a sulfur atom, group A is a group consisting of cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —COR a3 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , —COOR a1 , and —NR a2 COOR a3 ,
wherein R a1 and R a2 are the same or different and each is hydrogen atom, C 1-4 alkyl group or benzyl group and R a3 is C 1-4 alkyl group;
R 1 is a substituent selected from the following group B or a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atoms and the following group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from a C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A;
R 2 is selected from a hydrogen atom or a C 1-4 alkyl group;
R 31 is selected from a hydrogen atom, a cyano group, a hydroxy group, an amino group, a nitro group, a halogen atom, a C 1-4 alkyl group, a C 1-4 alkoxy group, a C 1-4 alkylsulfanyl group, a halo C 1-4 alkyl group, or a halo C 1-4 alkyloxy group;
X is selected from a C—R 32 or a nitrogen atom; and
Y is selected from a C—R 33 or a nitrogen atom,
wherein R 32 and R 33 are the same or different and each is selected from a hydrogen atom, cyano group, nitro group, halogen atom, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or, C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, —OR a7 , —SR a7 , —NR a7 R a8 , —NR a7 COR a9 , —COOR a10 , or —N═CH—NR a10 R a11 ,
wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B, or C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, R a9 is selected from C 1-4 alkyl group, and R a10 and R a11 are the same or different and each is selected from a hydrogen atom or C 1-4 alkyl group.
2. The method of claim 1 , wherein X is C—R 32 and Y is C—R 33 .
3. The method of claim 1 , wherein ring Cy is
wherein
R 4 and R 6 are the same or different and each is a substituent selected from the following group A,
wherein group A is a group consisting of cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —NR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —COR a3 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , —COOR a1 , and —NR a2 COOR a3 ,
wherein R a1 and R a2 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, or benzyl group, and R a3 is C 1-4 alkyl group;
R 5 is a substituent selected from hydrogen atom and group A, and R 4 and R 5 may form a fused ring together with a benzene ring they substitute; and
m is 0 or an integer of 1 to 3, and when m is 2 or 3, then R 6 of each m may be the same or different.
4. The method of claim 1 , wherein R 2 is a hydrogen atom.
5. A compound of formula [II] or a solvate thereof or a stereolsomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof:
wherein
R 4 and R 6 are the same or different and each is a substituent selected from the following group A,
wherein group A is a group consisting of cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —COR a3 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , —COOR a1 , and —NR a2 COOR a3 ,
wherein R a1 and R a2 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, or benzyl group, and R a3 is C 1-4 alkyl group;
R 5 is a substituent selected from hydrogen atom and the above-mentioned group A, and R 4 and R 5 may form a fused ring together with a benzene ring they substitute;
m is 0 or an integer of 1 to 3, and when m is 2 or 3, then R 6 of each m may be the same or different;
R 1 is a substituent selected from the following group B or a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the following group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom, and a sulfur atom as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 1-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A;
R 31 is selected from a hydrogen atom, a cyano group, a hydroxy group, an amino group, a nitro group, a halogen atom, a C 1-4 alkyl group, a C 1-4 alkoxy group, a C 1-4 alkylsulfanyl group, a halo C 1-4 alkyl group, or a halo C 1-4 alkyloxy group; and
R 32 and R 33 are the same or different and each is selected from
a hydrogen atom,
a cyano group,
a nitro group,
a halogen atom,
a C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A,
a heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, OR a7 , —SR a7 , —NR a7 R a8 , —NR a7 COR a9 , —COOR a10 , or —N═CH—NR a10 R a11 ,
wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B or C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, R a9 is C 1-4 alkyl group, and R a10 and R a11 are the same or different and each is selected from a hydrogen atom or C 1-4 alkyl group.
6. The compound of claim 5 , wherein R 31 is selected from a hydrogen atom, a cyano group, a hydroxy group, or a C 1-4 alkoxy group, or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
7. The compound of claim 6 , wherein R 31 is selected from a hydrogen atom, or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
8. The compound of claim 5 , wherein
R 32 and R 33 are the same or different and each is selected from
a hydrogen atom,
a cyano group,
a halogen atom,
a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group A,
wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom and a sulfur atom, and group A is a group consisting of cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —COR a3 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , —COOR a1 , and —NR a2 COOR a3 ,
wherein R a1 and R a2 are the same or different and each is hydrogen atom, C 1-4 alkyl group, or benzyl group, and R a3 is C 1-4 alkyl group,
a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the following group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A,
—OR a7 , —SR a7 , —NR a7 R a8 , —NR a7 COR a9 , —COOR a10 , or —N═CH—NR a10 R a11 ,
wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B, or C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, R a9 is C 1-4 alkyl group, and R a10 and R a11 are the same or different and each is selected from a hydrogen atom or C 1-4 alkyl group,
or a solvate thereof or a stereolsomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
9. The compound of claim 5 , wherein
R 32 is selected from a hydrogen atom, a cyano group, a halogen atom, a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the following group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom, and a sulfur atom) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A,
—OR a7 , —SR a7 , —NR a7 R a8 , —NR a7 COR a9 , or —COOR a10 ,
wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B, or C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, R a9 is C 1-4 alkyl group, and R a10 is selected from a hydrogen atom or C 1-4 alkyl group,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
10. The compound of claim 9 , wherein R 32 is selected from a hydrogen atom, —OR a7 , or —NR a7 R a8 , wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B, or C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B, or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
11. The compound of claim 8 , wherein
R 33 is selected from a hydrogen atom, a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the following group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom, and a sulfur atom) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A,
—OR a7 , or —NR a7 R a8
wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B, or C 1-10 alkyl group, optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
12. The compound of claim 11 , wherein
R 33 is selected from a hydrogen atom, —OR a7 , or —NR a7 R a8 ,
wherein R a7 and R a8 are the same or different and each is selected from a hydrogen atom, group B or C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the above-mentioned group B,
or a solvate thereof or a stereolsomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
13. The compound of claim 5 , wherein
R a7 and R a8
are the same or different and each is selected from a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the following group B, wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom and a sulfur atom) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
14. The compound of claim 5 , wherein
R 4 and R 5 are the same or different and each is a substituent selected from cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —NR a1 COR a3 , —SO 2 R a3 , —NR a2 COOR a3 , and —COOR a1 ,
wherein R a1 and R a2 are the same or different and each is hydrogen atom, C 1-4 alkyl group, or benzyl group, and R a3 is C 1-4 alkyl group,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
15. The compound of claim 14 , wherein
R 4 is selected from a phenyl group, a halogen atom, a C 1-4 alkyl group, a halo C 1-4 alkyloxy group, —OR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , or —COOR a1 ,
wherein R a1 and R a2 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group or benzyl group, and R a3 is C 1-4 alkyl group,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
16. The compound of claim 15 , wherein R 4 is a halogen atom, or a solvate thereof or a stereolsomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
17. The compound of claim 5 , wherein
R 5 is selected from a hydrogen atom, a cyano group, a phenyl group, a nitro group, a halogen atom, a C 1-4 alkyl group, a halo C 1-4 alkyl group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , or —NR a1 COR a3 ,
wherein R a1 and R a2 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, or benzyl group, and R a3 is C 1-4 alkyl group,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
18. The compound of claim 5 , wherein R 6 is a halogen atom, or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
19. The compound of claim 5 , wherein m is 0 or 1, or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
20. The compound of claim 5 , wherein
R 1 is selected from a C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the following group A,
wherein group A is a group consisting of cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —COR a3 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , —COOR a1 , and —NR a2 COOR a3 ,
wherein R a1 and R a2 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, or benzyl group, and R a3 is C 1-4 alkyl group,
a substituent selected from —NR a4 R a5 , —NR a4 COR a6 , —NR a4 SO 2 R a6 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom, and a sulfur atom) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or
a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 (wherein R a4 , R a5 , R a6 , and group A are as defined above),
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
21. The compound of claim 20 , wherein
R 1 is a C 1-10 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6 , —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A,
or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
22. A method for the treatment of an HIV infection, comprising: administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (III) or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof:
wherein
ring Cy is a C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the following group A or a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group A,
wherein the heterocyclic group is a saturated or unsaturated ring containing, besides carbon atom(s), at least one heteroatom selected from a nitrogen atom, an oxygen atom and a sulfur atom, group A is a group consisting of cyano group, phenyl group, nitro group, halogen atom, C 1-4 alkyl group, halo C 1-4 alkyl group, halo C 1-4 alkyloxy group, —OR a1 , —SR a1 , —NR a1 R a2 , —CONR a1 R a2 , —SO 2 NR a1 R a2 , —COR a3 , —NR a1 COR a3 , —SO 2 R a3 , —NR a1 SO 2 R a3 , —COOR a1 , and —NR a2 COOR a3 ,
wherein R a1 and R a2 are the same or different and each is selected from a hydrogen atom or C 1-4 alkyl group, and R a3 is C 1-4 alkyl group;
R 1 is a substituent selected from the following group B or a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from halogen atom and the following group B,
wherein group B is a group consisting of C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, —OR a4 , —SR a4 , —NR a4 R a5 , —CONR a4 R a5 , —SO 2 NR a4 R a5 , —COR a6 , —NR a4 COR a6, —SO 2 R a6 , —NR a4 SO 2 R a6 , —COOR a4 , and —NR a5 COOR a6 ,
wherein R a4 and R a5 are the same or different and each is selected from a hydrogen atom, C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, and R a6 is selected from C 1-4 alkyl group, C 3-10 carbon ring group optionally substituted by 1 to 5 substituents selected from the above-mentioned group A, or heterocyclic group (as defined above) optionally substituted by 1 to 5 substituents selected from the above-mentioned group A;
R 2 is selected from a hydrogen atom or a C 1-4 alkyl group;
R 3 is selected from a cyano group, a hydroxy group, an amino group, a nitro group, a halogen atom, a C 1-4 alkyl group, a C 1-4 alkoxy group, a C 1-4 alkylsulfanyl group, a halo C 1-4 alkyl group, or a halo C 1-4 alkyloxy group;
n is selected from 0 or an integer of 1 to 3 and when n is 2 or 3, R 3 each may be the same or different.
23. A pharmaceutical composition comprising a compound according to claim 5 , or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
24. A method for the treatment of an HIV infection, which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound according to claim 5 , or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
25. The method according to claim 24 , wherein the compound is administered at a dosage ranging from 0.01 mg to 1 g per administration for an adult.
26. The method according to claim 24 , wherein the compound is administered at a dosage for inhibiting activity specific for HIV integrase.
27. A method for inhibiting HIV integrase, comprising administering to a mammal in need thereof an HIV integrase inhibiting effective amount of a compound according to claim 5 or a solvate thereof or a stereoisomer thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
28. A method for the treatment of an HIV infection, comprising:
administering to a mammal in need thereof a composition comprising a therapeutically effective amount of a compound of the formula:
or a solvate thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
29. A method for inhibiting HIV integrase, comprising:
administering to a mammal in need thereof a composition comprising an HIV integrase inhibiting effective amount of a compound of the formula:
or a solvate thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
30. A compound of the formula:
or a solvate thereof or a tautomer thereof or a pharmaceutically acceptable salt thereof.
31. The method according to any one of claims 1 , 22 , 24 , 27 , 28 or 29 wherein the mammal is a human.