Anti-HCMV virus compound
Disclosed are a class of fused cyclic compounds against the HCMV virus, and use thereof in the preparation of a drugs for treating diseases associated with the HCMV virus. In particular, disclosed is the compound shown in formula (II) and pharmaceutically acceptable salts thereof.
1. A compound represented by formula (II), a pharmaceutically acceptable salt or a tautomer thereof,
wherein,
ring A is a 5-membered heteroaromatic ring;
R 1 is H or halogen, or selected from the group consisting of C 1-6 alkyl and C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 2 is H, or C 1-6 alkoxy which is optionally substituted by 1, 2 or 3 R;
R 3 is H, or selected from the group consisting of C 1-6 alkyl and C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
T is N or C(R);
n is 1 or 2;
Ar is selected from the group consisting of phenyl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 R;
R is H, F, Cl, Br, I, OH, CN, NH 2 or C(═O)NH 2 , or selected from the group consisting of C 1-6 alkyl and C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R′;
R′ is F, Cl, Br, I, OH, CN, NH 2 , COOH, Me, Et, CF 3 , CHF 2 , CH 2 F, NHCH 3 or N(CH 3 ) 2 ;
the heteroatom or heteroatom group in the 5-membered heteroaromatic ring, 6-membered heteroaryl or C 1-6 heteroalkyl is selected from the group consisting of —C(═O)NH—, —NH—, —S(═O) 2 NH—, —S(═O)NH, —O—, —S—, N, —C(═O)O—, —C(═O)—, —S(═O)— and —S(═O) 2 —;
in any of the above cases, the number of the heteroatom or the heteroatom group is independently 1, 2 or 3.
2. The compound the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 ,
wherein n is 1.
3. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, R is H, F, Cl, Br, I, OH, CN, NH 2 or C(═O)NH 2 , or selected from the group consisting of C 1-3 alkyl, (C 1-3 alkyl)-O—, (C 1-3 alkyl)-S—, (C 1-3 alkyl)-NH— and N,N′-di(C 1-3 alkyl)amino, each of which is optionally substituted by 1, 2 or 3 R′;
or, R is H, F, Cl, Br, I, OH, CN, NH 2 , C(═O)NH 2 , Me, Et,
4. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, ring A is thienyl, furyl, oxazolyl, isothiazolyl or isoxazolyl;
or, the moiety
5. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, R 1 is H, F, Cl, Br or I, or selected from the group consisting of C 1-3 alkyl, (C 1-3 alkyl)-O— and (C 1-3 alkyl)-S—, each of which is optionally substituted by 1, 2 or 3 R;
or, R 1 is H, F, Cl, Br or I, or selected from the group consisting of Me and Et, each of which is optionally substituted by 1, 2 or 3 R;
or, R 1 is H, F, Cl, Br, I, Me or Et.
6. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, R 2 is H or (C 1-3 alkyl)-O— which is optionally substituted by 1, 2 or 3 R;
or, R 2 is H or
which is optionally substituted by 1, 2 or 3 R;
or, R 2 is H,
7. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, R 3 is H, or selected from the group consisting of C 1-3 alkyl, (C 1-3 alkyl)-O— and (C 1-3 alkyl)-S—, each of which is optionally substituted by 1, 2 or 3 R;
or, R 3 is H, or selected from the group consisting of Me, Et and
each of which is optionally substituted by 1, 2 or 3 R;
or, R 3 is H, Me, Et, CF 3 ,
8. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, T is N, CH, C(F), C(Cl), C(Br) or C(I).
9. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 2 , wherein, Ar is selected from the group consisting of phenyl, pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl, each of which is optionally substituted by 1, 2 or 3 R;
or, Ar is selected from the group consisting of
each of which is optionally substituted by 1, 2 or 3 R;
or, Ar is
10. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 4 , wherein, the moiety
11. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, R is H, F, Cl, Br, I, OH, CN, NH 2 or C(═O)NH 2 , or selected from the group consisting of C 1-3 alkyl, (C 1-3 alkyl)-O—, (C 1-3 alkyl)-S—, (C 1-3 alkyl)-NH— and N,N′-di(C 1-3 alkyl)amino, each of which is optionally substituted by 1, 2 or 3 R′;
or, R is H, F, Cl, Br, I, OH, CN, NH 2 , C(═O)NH 2 , Me, Et,
12. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, ring A is thienyl, furyl, oxazolyl, isothiazolyl or isoxazolyl;
or, the moiety
13. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, R 1 is H, F, Cl, Br or I, or selected from the group consisting of C 1-3 alkyl, (C 1-3 alkyl)-O— and (C 1-3 alkyl)-S—, each of which is optionally substituted by 1, 2 or 3 R;
or, R 1 is H, F, Cl, Br or I, or selected from the group consisting of Me and Et, each of which is optionally substituted by 1, 2 or 3 R;
or, R 1 is H, F, Cl, Br, I, Me or Et.
14. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, R 2 is H or (C 1-3 alkyl)-O— which is optionally substituted by 1, 2 or 3 R;
or, R 2 is H or
which is optionally substituted by 1, 2 or 3 R;
or, R 2 is H,
15. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, R 3 is H or selected from the group consisting of C 1-3 alkyl, (C 1-3 alkyl)-O— and (C 1-3 alkyl)-S—, each of which is optionally substituted by 1, 2 or 3 R;
or, R 3 is H, or selected from the group consisting of Me, Et and
each of which is optionally substituted by 1, 2 or 3 R;
or, R 3 is H, Me, Et, CF 3 ,
16. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, T is N, CH, C(F), C(Cl), C(Br) or C(I).
17. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, Ar is selected from the group consisting of phenyl, pyridyl, pyrimidinyl, pyrazinyl and pyridazinyl, each of which is optionally substituted by 1, 2 or 3 R;
or, Ar is selected from the group consisting of
each of which is optionally substituted by 1, 2 or 3 R;
or, Ar is selected from the group consisting of
18. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 12 , wherein, the moiety
19. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , wherein, the moiety
20. The compound, the pharmaceutically acceptable salt or the tautomer thereof as defined in claim 1 , which is selected from the group consisting of
wherein,
R 1 , R 3 and R are as defined in claim 1 ;
T 1 is N or CH;
or, is selected from the group consisting of
wherein,
R 1 , R 3 and R are as defined in claim 1 ;
T 1 is N or CH.
21. A compound, a pharmaceutically acceptable salt or a tautomer thereof, which is selected from the group consisting of
or, is selected from the group consisting of
22. A pharmaceutical composition, comprising the compound, the pharmaceutically acceptable salt or the tautomer as defined in claim 1 , as well as one or more than one pharmaceutically acceptable excipient.
23. A pharmaceutical composition, comprising the compound, the pharmaceutically acceptable salt or the tautomer as defined in claim 21 , as well as one or more than one pharmaceutically acceptable excipient.
24. A method for treating a human cytomegalovirus (HCMV) infection in a patient in need thereof, comprising administering to the patient a medicament comprising an effective amount of the compound, the pharmaceutically acceptable salt or the tautomer as defined in claim 1 .
25. A method for treating a human cytomegalovirus (HCMV) infection in a patient in need thereof, comprising administering to the patient a medicament comprising an effective amount of the compound, the pharmaceutically acceptable salt or the tautomer as defined in claim 21 .