Quinazoline derivative as phosphodiesterase inhibitor and a process for preparing the same

A novel quinazoline derivative is provided to inhibit selectively phosphodiesterase V(PDE V), thereby being usefully used as a therapeutic agent of cardiovascular diseases. A quinazoline derivative is represented by a formula(I), wherein R1 is NO, NH2, CN, CON(K), CON(K)2, COO(K), COO(K)2, or a group represented by the structural formula(1), (2) or (3)(where K is H, or C1-6 alkyl; R4 is H, C1-6 alkyl, halogenated methyl, cyanomethyl, cycloalkyl, C1-6 alkylamino, C1-6 dialkylamino, CF3, C6-12 arylalkyl, C1-3 alkoxy, or heterocyclyl-(C1-6) alkyl; R5 is C1-6 alkyl, or phenyl; n is 0, 1, or 2; Rd is H, or C1-3 alkyl); R2 is fluoro, chloro, hydroxy, C1-6 alkoxy, or -O-Z(where Z is a compound represented by the structural formula(4) or (5)(where m is an integer from 2 to 5; each R6 and R7 is independently H, C1-6 alkyl; p is an integer from 1 to 6; and R8 is hydroxy, alkoxy or amino)), provided that R1 and R2 may form a compound represented by the structural formula(6)(where A is CR9 or C(O); B is O or NR10); R3 is C1-6 alkyl, C1-6 alkenyl, or a compound represented by the structural formula(7) or (8)(where q is 0, 1, 2, or 3; Q is C(O)H, -N(R11)(R12), -O(R13), or -C(O)R14), provided that R2 and R3 may form a compound represented by the structural formula(9); each Ra and Rb is independently halogen, C1-6 alkyl, C1-6 alkoxy, hydroxy, or methylenedioxy; and Rc is H, chloro, dimethylamine, heterocycle, or a compound represented by the structural formula(10), (11), (12) or (13)(where R16 is hydroxy, CO2H or C1-6 ester; E is C, O, S or C1-6 alkylamine; s is 0 or 1; R17 is H or hydroxy; and r is an integer from 2 to 5). A pharmaceutical composition for treating cardiovascular diseases such as impotence, angina pectoris, hypertension, pulmonary hypertension and atherosclerosis comprises: the compound of the formula(1), an isomer thereof, or a pharmaceutically acceptable salt thereof; a solvate thereof or a hydrate thereof and a pharmaceutically acceptable carrier.