Structure-activity relationship studies of CNS agents .29. N-methylpiperazino-substituted derivatives of quinazoline, phthalazine and quinoline as novel alpha(1), 5-HT1A and 5-HT2A receptor ligands

被引：20

作者：

Mokrosz, JL ^{[1
]}

Duszynska, B ^{[1
]}

CharakchievaMinol, S ^{[1
]}

Bojarski, AJ ^{[1
]}

Mokrosz, MJ ^{[1
]}

Wydra, RL ^{[1
]}

Janda, L ^{[1
]}

Strekowski, L ^{[1
]}

机构：

[1] GEORGIA STATE UNIV,DEPT CHEM,ATLANTA,GA 30303

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 31卷 / 12期

关键词：

N-methylpiperazine; prazosin analog; alpha(1) receptor ligands; 5-HT1A receptor ligands; 5-HT2A receptor ligands; structure-affinity relationships;

D O I：

10.1016/S0223-5234(97)86176-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New N-methylpiperazino-substituted quinazolines 8 and 9, phthalazine 13, and quinoline 19 have been synthesized. The receptor binding profiles (alpha(1), 5-HT1A, 5-HT2A) of these compounds and their analogs (7-22) have been determined. It has been demonstrated that orientation of a local dipole moment of the heteroaromatic ring system affects both the alpha(1) and 5-HT2A affinity of the investigated class of ligands. Distortion of the coplanar unfused heteroaromatic ring system results in a decreased 5-HT2A affinity. 4-(4-Methylpiperazino)-2-(2-thienyl)quinoline 18 is the most active and selective alpha(1) ligand (K-i = 4.9 nM) with a much lower affinity for 5-HT1A (K-i = 3420 nM) and 5-HT2A (K-i = 211 nM) receptors.

引用

页码：973 / 980

页数：8

共 35 条

[1] 2,4-DIAMINO-6,7-DIMETHOXYQUINAZOLINES .2. 2-(4-CARBAMOYLPIPERIDINO) DERIVATIVES AS ALPHA-1-ADRENOCEPTOR ANTAGONISTS AND ANTIHYPERTENSIVE AGENTS [J].