Zhang, Dehui published the artcileIsoquinolone derivatives as lysophosphatidic acid receptor 5 (LPA5) antagonists: Investigation of structure-activity relationships, ADME properties and analgesic effects, Category: bromides-buliding-blocks, the main research area is isoquinolone preparation analgesic LPA5 antagonism SAR; Analgesic; Antagonist; Brain penetrant; LPA5; Structure-activity relationship.
A series of isoquinolone derivatives were designed and synthesized and their potency in LPA5 calcium mobilization and cAMP assays were evaluated. The results showed that substituted Ph groups or bicyclic aromatic rings such as benzothiophenes or benzofurans are tolerated at the 2-position, 4-substituted piperidines are favored at the 4-position, and methoxy groups at the 6- and 7-positions are essential for activity. Compounds I and II showed comparable in vitro potency, excellent selectivity against LPA1-LPA4 and >50 other GPCRs, moderate metabolic stability, and high aqueous solubility and brain permeability. Both I and II significantly attenuated nociceptive hypersensitivity at lower doses than III and had longer-lasting effects in an inflammatory pain model, and II also dose-dependently reduced mech. allodynia in the chronic constriction injury model and opioid-induced hyperalgesia at doses that had no effect on the locomotion in rats. These results suggest that these isoquinolone derivatives as LPA5 antagonists are of promise as potential analgesics.
European Journal of Medicinal Chemistry published new progress about Analgesics. 74317-85-4 belongs to class bromides-buliding-blocks, name is 2-Bromo-4-methoxybenzoic acid, and the molecular formula is C8H7BrO3, Category: bromides-buliding-blocks.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary