Sakauchi, Nobuki; Kohara, Yasuhisa; Sato, Ayumu; Suzaki, Tomohiko; Imai, Yumi; Okabe, Yuichi; Imai, Shigemitsu; Saikawa, Reiko; Nagabukuro, Hiroshi; Kuno, Haruhiko; Fujita, Hisashi; Kamo, Izumi; Yoshida, Masato published the artcile< Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1D Adrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-go-Related Gene (hERG) Liabilities>, Product Details of C8H6ClN, the main research area is adrenoceptor antagonist incontinence hERG; crystal structure adrenoceptor antagonist incontinence.
A novel structural class of iminopyridine derivative 1 was identified as a potent and selective human α1D adrenoceptor (α1D adrenergic receptor; α1D-AR) antagonist against α1A- and α1B-AR through screening of an inhouse compound library. From initial structure-activity relationship studies, we found lead compound 9m with hERG K+ channel liability. To develop analogs with reduced hERG K+ channel inhibition, a combination of site-directed mutagenesis and docking studies was employed. Further optimization led to the discovery of I and II, which showed antagonistic activity by a bladder strip test in rats with bladder outlet obstruction, as well as ameliorated cystitis-induced urinary frequency in rats. Ultimately, 9u was selected as a clin. candidate. This is the first study to show the utility of iminopyridine derivatives as selective α1D-AR antagonists and evaluate their effects in vivo.
Journal of Medicinal Chemistry published new progress about Androgen receptor antagonists. 21423-84-7 belongs to class nitriles-buliding-blocks, and the molecular formula is C8H6ClN, Product Details of C8H6ClN.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts