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 addition salt, or a stereochemically isomeric form thereof, wherein
-a 1 =a 2 -a 3 =a 4 - represents a bivalent radical of formula
—CH═CH—CH═CH— (a-1);
-b 1 -b 2 -b 3 - represents a bivalent radical of formula
—O—CH 2 —CH 2 — (b-1);
—O—CH═CH— (b-2);
—CH 2 —CH═CH— (b-5);
n is 1;
m is 0, 1;
q is 1,2;
R 1 is hydrogen;
R 2 is halo, nitro, cyano, —CONH 2 , C 1-6 alkyl optionally substituted with cyano or with —CONH 2 ;
X 1 is —NH—, —O—;
R 3 is hydrogen, halo, C 1-6 alkyl;
R 4 is halo, C 1-6 alkyl;
R 13 and R 14 each independently are hydrogen, C 1-6 alkyl;
R 17 is cyano, halo, C 1-6 alkyl optionally substituted with cyano; C 2-6 alkenyl optionally substituted with cyano; and, where possible, R 17 may also be attached to the -b 1 -b 2 -b 3 -moiety by a double bond whereby R 17 is ═O; the R 17 moiety attached to a carbon atom in the -b 1 -b 2 -b 3 ring;
Q represents hydrogen;
Z is C—Y, wherein Y is hydrogen or halo.
2. The compound of claim 1 wherein:
n is 1;
q is 1.
3. The compound of claim 1 wherein R 2 is cyano.
4. The compound of claim 1 wherein Y is hydrogen.
5. The compound of claim 1 wherein R 17 is cyano, C 1-6 alkyl substituted with cyano, C 2-6 alkenyl substituted with cyano; or R 17 is ═O.
6. The compound of claim 1 wherein
-b 1 -b 2 -b 3 - represents a bivalent radical of formula
—O—CH 2 —CH 2 — (b-1);
n is 1;
m is 0;
q is 1;
R 2 is cyano;
Y is hydrogen;
R 17 is ═O.
7. The compound of claim 1 wherein
-b 1 -b 2 -b 3 - represents a bivalent radical of formula
—O—CH═CH— (b-2);
n is 1;
m is 0;
q is 1;
R 2 is cyano;
Y is hydrogen;
R 17 is C 1-6 alkyl substituted with cyano.
8. The compound of claim 1 wherein
-b 1 -b 2 -b 3 - represents a bivalent radical of formula,
—CH 2 —CH═CH— (b-5);
n is 1;
m is 0;
q is 1;
R 2 is cyano;
R 3 is halo;
Y is hydrogen;
R 17 is C 1-6 alkyl substituted with cyano.
9. A pharmaceutical composition comprising an effective amount, against HIV infection, of a compound of claim 1 , in a pharmaceutically acceptable carrier.
10. A pharmaceutical composition of claim 9 and another antiretroviral compound.
11. A method of treating HIV infection by administering to a human subject in need of such treatment, an anti-HIV effective amount of a compound of claim 1 .