Discovery of novel, potent, and orally bioavailable pyrido[2,3-d][1]benzazepin-6-one antagonists for parathyroid hormone receptor 1.

Discovery of novel, potent, and orally bioavailable pyrido[2,3-d][1]benzazepin-6-one antagonists for parathyroid hormone receptor 1.
Bioorg Med Chem. 2020 Apr 22;:115524
Authors: Arai Y, Kiyotsuka Y, Kagechika K, Nishi T, Inui M, Nagamochi M, Oyama K, Izumi M
Abstract
Structural modification of a 1,4-benzodiazepin-2-one-based PTHR1 antagonist 5, a novel type of PTHR1 antagonist previously synthesized in our laboratories, yielded compound 10, which had better chemical stability than compound 5. Successive optimization of the lead 10 improved aqueous solubility, metabolic stability, and animal pharmacokinetics, culminating in the identification of DS37571084 (12). Our study paves the way for the discovery of novel and orally bioavailable PTHR1 antagonists.
PMID: 32345459 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - April 21, 2020 Category: Chemistry Authors: Arai Y, Kiyotsuka Y, Kagechika K, Nishi T, Inui M, Nagamochi M, Oyama K, Izumi M Tags: Bioorg Med Chem Source Type: research