DIHYDROQUINAZOLINE DERIVATIVES

摘要

Pharmaceutical compositions comprising, or compositions consisting essentially of, compounds according to the formula or an optical isomer thereof wherein Z is oxygen or NR<2>; n is an integer of 1 to 6; R<1> and R<2> are independently hydrogen; alkyl of 1 to 12 carbon atoms; cycloalkyl of 3 to 12 carbon atoms; hydroxalkyl of 1 to 6 carbon atoms; cycloalkyl lower alkyl of 4 to 12 carbon atoms wherein the cycloalkyl ring is optionally substituted with a lower alkyl, lower alkoxy, -OH, -OCOR<3>, halo, -N(R<3>)2, -NHCOR<3>, -COOH, or -COOR<3> group wherein R<3> is lower alkyl; and phenyl or phenyl lower alkyl wherein phenyl is optionally substituted with at least one lower alkyl, halo or lower alkoxy group or an -N(R<3>)2, -NHCOR<3>, -COOH, or -COOR<3> group wherein R<3> is lower alkyl; or R<1> and R<2> are combined with the N to which they are attached to form a cyclic secondary amine radical having from 5 to 8 atoms, where, in addition to the N atom, the atoms in the radical comprise carbon atoms and can include one oxygen or sulfur atom, or one optionally lower alkyl substituted nitrogen atom; HX is optionally present and when present represents the acid portion of a pharmaceutically acceptable acid additional salt; A is NR<4>R<5> wherein R<4> and R<5> are independently selected from the group consisting of: hydrogen; alkyl of 1 to 6 carbon atoms; hydroxyalkyl of 2 to 6 carbon atoms; cycloalkyl of 3 to 8 carbon atoms or cycloalkyl lower alkyl of 4 to 12 carbon atoms wherein the cycloalkyl ring is optionally substituted with a lower alkyl, lower alkoxy, -OH, -OCOR<3>, halo, -N(R<3>)2, -NHCOR<3>, -COOH, or -COOR<3> group wherein R<3> is lower alkyl; and phenyl or phenyl lower alkyl wherein phenyl is optionally substituted with at least one lower alkyl, halo or lower alkoxy group or an -N(R<3>)2, -NHCOR<3>, -COOH, or -COOR<3> group wherein R<3> is lower alkyl; or wherein R<4> and R<5> are combined to form a compound selected from the group consisting of: morpholinyl, piperidinyl, perhexylenyl, N-loweralkylpiperazinyl, pyrrolidinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, (+/-)-decahydroquinolinyl and indolinyl. The invention is also directed to certain compounds of the above class. The compounds of Formula I are cyclic AMP phosphodiesterase inhibitors useful as antithrombotic and inotropic agents and the like in mammals.