Aquaretics

Thibonnier, Marc

doi:10.1517/14728214.4.1.223

Cited by 4 publications

(1 citation statement)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The V 2 receptor inhibitors shut off cAMP and aquaporin 2 production, so that water is released as urine, with little effect on the urinary sodium and potassium excretion, which is at variance with classical natriuretic agents. The term "aquaretics" has been coined to describe this class of agents [25].…”

Section: Arginine Vasopressin Receptors and Their Non-peptide Inhibitorsmentioning

confidence: 99%

Chemical development of the vasopressin receptor 2 antagonist SR-121463

Hermecz¹,

Sánta-Csutor

Gönczi

et al. 2001

Pure and Applied Chemistry

View full text Add to dashboard Cite

A facile convergent total synthesis of the selective, potent, and orally active V 2 nonpeptide antagonist, SR-121463, was developed by modification of the discovery route. One of the late intermediates, the sulfonyl chloride 1, was synthesized from 3-hydroxybenzoic acid (19) by regioselective sulfonation, O-methylation and amidation in four steps. Another late intermediate, indolin-2-one 2, was prepared from p-phenetidine (8) through the indolin-2-one 16, where the cyclohexanone moiety of 27 was introduced into the active 3-methylene group of 16 by sequential transformation using methyl acrylate and KOtBu. After formation of the cyclic ketal moiety of 13, its ring-opening was achieved by using NaBH 4 in the presence of CCl 3 COOH. The morpholino group in 2 was introduced in accordance with the discovery approach, starting from the 2-hydroxyethoxy derivative 14 through the tosyloxy derivative 15 with morpholine in a one-pot reaction. In this way, the indolin-2-one 2 was synthesized from 8 in six steps. Finally, acylation of the indolin-2-one 2 was achieved with the sulfonyl chloride 1 in the presence of KOtBu in dimethyl sulfoxide (DMSO) at room temperature. This synthetic route proved to be applicable for the large-scale synthesis of SR-121463.

show abstract

Section: Arginine Vasopressin Receptors and Their Non-peptide Inhibitorsmentioning

confidence: 99%