Synthesis of heteroaromatic potential .beta.-adrenergic antagonists by the glycidol route

Abstract

The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity.

Medicinal Chemistry and Properties of 1,2,4-Thiadiazoles

“…Interestingly, the simple THD analogue (22) showed antibacterial activity [23]. Analogues of 1,2,4-thiadiazole have also been studied as potential adenosine receptor antagonists [24], as β-adrenergic antagonists [25], and for their muscarinic activities [26]. Recently, a 1,2,4-thiadiazole derivative has been reported to bind in the benzodiazepine binding site of human γ -aminobutyric acid receptor ion channels [27].…”

Synthesis of 3-Substituted Bicyclic Imidazo[1,2-d][1,2,4]thiadiazoles and Tricyclic Benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazoles

“…In recent years, many biologically active [1,2,4]THDs exhibiting interesting medicinal properties for the potential treatment of human diseases have been disclosed. − The injectable cephalosporin antibiotic cefozopran hydrochloride ( 2 ), which has a monocyclic THD group was launched as Firstcin in Japan in 1995 (Figure ) . However, the role and importance of the THD moiety in all of those compounds, with regards to the mechanism of the biological response of the targeted enzymes, are not clearly understood at the molecular level.…”