Synthesis and Blocking Activities of a New Class of α₁‐Adrenoceptor Antagonists

Abstract

Finding effective chemotherapeutic agents for clinical use is a long‐lasting goal in medicinal chemistry. In this study, we report a new class of α1‐adrenoceptor (α1‐AR) antagonists. Specifically, we describe the synthesis and the blocking activities toward α1‐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, 1H 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 α1‐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 α1‐AR antagonists.

N-Chloroformylimidazolidinone Enolates as 1,3-Dipolar Reagents for the Stereoselective Synthesis of 3,4-Dihydroisoquinolones

“…The 3,4-dihydroisoquinolone − core represents an important structural motif found among a wide variety of natural products (Figure ). − The dihydroisoquinolone skeleton also displays a range of biological activities, , including anti-inflammatory, anticancer, and antiangiogenic characteristics.…”

A Synthesis of 3,4-Dihydroisoquinolin-1(2H)-one via the Rhodium-Catalyzed Alkylation of Aromatic Amides with N-Vinylphthalimide

“…3,4-Dihydroisoquinolin-1­(2H)-one and derivatives thereof are important types of alkaloids that are widely distributed in natural products (Figure ). , Because many of these compounds are biologically active and are also stable, they are often used in preparing biomolecules and pharmaceuticals. − Although several methods for preparing isoquinolinones and their derivatives have been reported, a highly efficient method for achieving these compounds continues to be an attractive area of research in organic chemistry. − …”

Design, Synthesis and Biological Evaluation of Novel 7-Mercaptocoumarin Derivatives as α₁-Adrenoceptor Antagonists

“…[30][31][32][33][34][35] The rat anococcygeus smooth muscles were selected as muscle preparations because their contractions are primarily mediated by α 1 -ARs, and they have neither spontaneous activity nor tone and can survive for a long time in vitro. [36][37][38][39] The activity was expressed as pA 2 =−log[1-24] 2 , in which 2 is defined as the measured concentrations of the compounds 1-24 according to Schild's methods.…”