HIV replication inhibiting pyrimidines and triazines
View Patent ↗This invention concerns HIV replication inhibitors of formula (I), the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.
1. A compound of formula (I)
a pharmaceutically acceptable acid or base addition salt, or a stereochemically isomeric form thereof, wherein
Z is C-H;
n is 1 or 2;
m is 0 or 1;
q is 0 or 1;
R 1 is hydrogen;
R 2 is independently hydroxyl; halo; C 1-6 alkyl optionally substituted with cyano or with —C(═O)—NH 2 ; cyano; nitro; —C(═O) —NH 2 ; or a radical of formula
X 1 is —NH— or —O—;
R 3 is hydrogen, halo, or C 1-6 alkyl;
R 4 is halo or C 1-6 alkyl;
R 17 is C 1-6 alkyl optionally substituted with cyano; —C(═O)—NR 13 R 14 ; or C 2-6 alkenyl optionally substituted with cyano; or R 17 is attached to the ring by a double bond, and is ═O, ═CH 2 ; ═CHCN; ═CH—C(═O)—NR 13 R 14 ; or ═N—O—C 1-6 alkyl-phenyl;
Q is hydrogen or —C(═O)—NR 13 R 14 ; and
R 13 and R 14 are each independently hydrogen or C 1-6 alkyl.
2. A compound according to claim 1 wherein R 2 is cyano.
3. A compound according to claim 2 wherein
n is 1;
m is 1; and
R 13 and R 14 are hydrogen.
4. A compound according to claim 2 wherein
n is 1;
m is 0; and
R 13 and R 14 are hydrogen.
5. A compound according to claim 1 wherein
n is 1;
m is 0 and
R 4 is chloro.
6. A compound according to claim 1 wherein
n is 1;
m is 0 and
R 3 and R 4 are methyl.
7. A compound according to claim 1 wherein
R 17 is C 1-6 alkyl substituted with cyano; or ═CHCN.
8. A compound according to claim 2 wherein
Q is hydrogen;
n is 1;
m is 1;
R 17 is C 1-6 alkyl substituted with cyano; or ═CHCN.
9. A pharmaceutical composition comprising an effective amount, for the treatment of HIV infection, of a compound of claim 1 , in a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising an effective amount, for the treatment of HIV infection, of a compound of claim 1 , and an anti-HIV effective amount of a second antiretroviral compound, in a pharmaceutically acceptable carrier.
11. A method of treating HIV infection by administering to a human subject in need of such treatment, an effective amount of a compound of claim 1 .