Terakado, Masahiko; Suzuki, Hidehiro; Hashimura, Kazuya; Tanaka, Motoyuki; Ueda, Hideyuki; Kohno, Hiroshi; Fujimoto, Taku; Saga, Hiroshi; Nakade, Shinji; Habashita, Hiromu; Takaoka, Yoshikazu; Seko, Takuya published the artcile< Discovery of ONO-7300243 from a Novel Class of Lysophosphatidic Acid Receptor 1 Antagonists: From Hit to Lead>, Recommanded Product: Methyl 4-chloro-2-hydroxybenzoate, the main research area is ONO7300243 preparation lysophosphatidate receptor 1 antagonist drug discovery; GPCR; LPA1 antagonist; SAR; benign prostatic hyperplasia; hit-to-lead optimization.
Lysophosphatidic acid (LPA) evokes various physiol. responses through a series of G protein-coupled receptors known as LPA1-6. A high throughput screen against LPA1 gave compound 4′-{[(4-methoxybenzoyl)(3-phenylpropyl)amino]methyl}-2-biphenylcarboxylic acid (7a) as a hit. The subsequent optimization of 7a led to ONO-7300243 (17a) as a novel, potent LPA1 antagonist, which showed good efficacy in vivo. The oral dosing of 17a at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, this compound was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clin. practice to treat dysuria with benign prostatic hyperplasia (BPH). In contrast to tamsulosin, compound 17a had no impact on the mean blood pressure at this dose. These results suggest that LPA1 antagonists could be used to treat BPH without affecting the blood pressure. Herein, the authors report the hit-to-lead optimization of a unique series of LPA1 antagonists and their in vivo efficacy.
ACS Medicinal Chemistry Letters published new progress about Benign prostatic hyperplasia. 22717-55-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Recommanded Product: Methyl 4-chloro-2-hydroxybenzoate.
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics