Tetrahydroquinazoline-2,4-diones and therapeutic uses thereof

The present invention is directed to 4-(4-phenyl-1,2,3,6-tetrahydropyridin-1yl)-propyl-1,2,3,4-tetrahydroquinazoline-2,4-dione compounds, and pharmaceutically acceptable salts thereof, as well as to the use of these compounds to selectively block serotonin reuptake and 5-HT receptor binding in mammalian central nervous systems (CNS). The present invention is also directed to the use of these compounds in a methods of treatment of various diseases, disorders and conditions, as well as pharmaceutical compositions useful therefor. Further, the present invention is directed to methods for the preparation of 4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)propyl-1,2,3,4-tetrahydroquinazoline-2,4-dione compounds and intermediates useful therefore. The present invention relates to tetrahydroquinazoline-2,4-diones derivatives of the formula (I): pharmaceutically acceptable salts thereof, wherein A is (CH)where n is equal to 0, 1 or 2; U is CH, NH, or NR, Rand Rare selected independently from H, (C-C)alkyl, Cl, F, CN, nitro, CF, -NHC(O)Rand -OR, or Rand R, together with the atoms to which they are attached, form a carbocyclic or heterocyclic five- or six-membered ring, Ris selected from the group consisting of H, (C-C)alkyl, C( O)-(C-C)alkyl, where m=1 or 2; Rand Rare selected from H, (C-C)alkyl, Cl, F, -CF, -CN, -NHC( O)R, -OR, a 5-to 7-membered aryl or heteroaryl ring, where m, Rand Rare as defined above; and Rand Rare selected independently from H, (C-C)alkyl or a 5- to 7-membered aryl or heteroaryl ring; V is CH, CR, or N; W is CH, C(O), or S(O); X is C or N; and Y is CH, CR,CR, or N. The invention also relates to pharmaceutical compositions containing the same and to methods of use thereof, including in the inhibition of serotonin reuptake, the inhibition of the binding of 5-HTserotonin receptors and the treatment of diseases, conditions or disorders of the central nervous system. Further, the present invention is also directed to methods for the preparation of 4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)-propyl-1,2,3,4-tetrahydroquinazoline-2,4-dione compounds and intermediates useful thereof.