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Synthesis and Blocking Activities of a New Class of α 1 ‐Adrenoceptor Antagonists
Author(s) -
Xi BaoMin,
Ni PeiZhou,
Jiang ZhenZhou,
Wu DianQing,
Zhang ShouHua,
Zhang HuiBin,
Wang Tao,
Chen WenHua
Publication year - 2010
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2010.01040.x
Subject(s) - blocking (statistics) , chemistry , lead compound , tamsulosin , combinatorial chemistry , antagonist , stereochemistry , pharmacology , hydrochloride , receptor , biochemistry , in vitro , computer science , biology , medicine , computer network , hyperplasia
Finding effective chemotherapeutic agents for clinical use is a long‐lasting goal in medicinal chemistry. In this study, we report a new class of α 1 ‐adrenoceptor (α 1 ‐AR) antagonists. Specifically, we describe the synthesis and the blocking activities toward α 1 ‐AR of 7‐(2‐hydroxypropoxy)‐3,4‐dihydroisoquinolin‐1(2H)‐one 1 and its structurally perturbed analogs 2 – 11 that were designed according to the principle of bioisosterism. Their structures were identified with IR, 1 H NMR, MS, HRMS and elemental analysis. The blocking activities of compounds 1 – 11 were evaluated on isolated rat anococcygeus muscles. The results indicated that these compounds showed moderate to good activities. Among them, compound 1 exhibited the highest activity that was comparable to those of known α 1 ‐AR antagonists tamsulosin and DDPH (1‐(2,6‐dimethylphenoxy)‐2‐(3,4‐di‐ methoxyphenylethylamino)propane hydrochloride) and thus may be exploitable as a lead compound for the discovery of promising α 1 ‐AR antagonists.