HIV inhibiting 5-amido substituted pyrimidines
View Patent ↗This invention concerns pyrimidine derivatives of formula having HIV (Human Immunodeficiency Virus) replication inhibiting properties, the preparation thereof and pharmaceutical compositions comprising these compounds.
1. A compound having the following structure:
wherein:
R 5 is selected from C 3-7 cycloalkyl; C 1-6 alkyloxy; aryl; Het; C 1-6 alkyl substituted with a radical selected from hydroxy, C 1-6 alkyloxy, cyano, amino, mono- and di-C 1-6 alkylamino, C 1-6 alkylcarbonylamino, aryl, Het, dioxolanyl optionally substituted with one or two C 1-6 alkyl radicals, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, piperazinyl optionally substituted with C 1-6 alkyl or C 1-6 alkylcarbonyl, C 1-6 alkyloxycarbonyl, arylC 1-6 alkyloxycarbonyl, or C 3-7 cycloalkyl; and is C 1-6 alkyl substituted with two C 1-6 alkyloxy radicals;
R 6 is selected from hydrogen and C 1-6 alkyl; or
R 5 and R 6 taken together with the nitrogen atom to which they are attached form pyrrolidinyl; piperidinyl; morpholinyl; piperazinyl; or piperazinyl optionally substituted with C 1-6 alkyl or C 1-6 alkylcarbonyl.
2. A compound according to claim 1 , wherein:
R 5 is C 3-7 cycloalkyl; C 1-6 alkyloxy; aryl; Het; C 1-6 alkyl substituted with a radical selected from hydroxy, C 1-6 alkyloxy, cyano, di-C 1-6 alkylamino, C 1-6 alkylcarbonyl amino, aryl, Het, dioxolanyl substituted with two C 1-6 alkyl radicals, tetrahydrofuranyl, pyrrolidinyl, C 1-6 alkyloxycarbonyl, and C 3-7 cycloalkyl;
R 6 is hydrogen or C 1-6 alkyl; or
R 5 and R 6 taken together with the nitrogen atom to which they are substituted form morpholinyl; piperazinyl substituted with C 1-6 alkyl.
3. A compound according to claim 1 , wherein R 5 is C 3-7 cycloalkyl; C 1-6 alkyloxy; C 1-6 alkyl substituted with a radical selected from hydroxy, C 1-6 alkyloxy, cyano, C 1-6 alkylcarbonylamino, aryl, Het, C 1-6 alkyloxycarbonyl; and R 6 is hydrogen.
4. A compound according to claim 1 , wherein each Het independently is pyridyl, thienyl, thiazolyl, furanyl, each of which may be optionally substituted with a radical selected from C 1-6 alkyl.
5. A compound according to claim 1 , wherein each aryl independently may be phenyl optionally substituted with C 1-6 alkylamino, mono- or di-C 1-6 alkyl-amino, C 1-6 alkyloxy, aminosulfonyl, Het, the latter more in particular being thiadiazolyl.
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1 .
7. A compound according to claim 1 , having the following structure:
8. A compound according to claim 1 , having the following structure:
9. A compound according to claim 1 , having the following structure:
10. A compound according to claim 1 , having the following structure:
11. A compound according to claim 1 , having the following structure: