Chemical Research Letters, May 2021. Chemistry is a science major with cience and engineering. The main research directions are chemical synthesis, and research on the structure and performance of functional materials. In an article, author is Ramsden, Diane, once mentioned the application of 136-95-8, Name is Benzo[d]thiazol-2-amine. Now introduce a scientific discovery about this category, Formula: https://www.ambeed.com/products/136-95-8.html.
During drug discovery efforts targeting inhibition of cytochrome P450 11B2 (CYP11B2)-mediated production of aldosterone as a therapeutic approach for the treatment of chronic kidney disease and hypertension, (S)-6-(5-fluoro-4-(1-hydroxyethyl)pyridin-3-yl)3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (1) was identified as a potent and selective inhibitor of CYP11B2. Preclinical studies characterized 1 as low clearance in both in vitro test systems and in vivo in preclinical species. Despite low metabolic conversion, an active ketone metabolite (2) was identified from in vitro metabolite-identification studies. Due to the inhibitory activity of 2 against CYP11B2 as well as the potential for it to undergo reductive metabolism back to 1, the formation and elimination of 2 were characterized and are the focus of this manuscript. A series of in vitro investigations determined that 1 was slowly oxidized to 2 by cytochrome P450s 2D6, 3A4, and 3A5, followed by stereoselective reduction back to 1 and not its enantiomer (3). Importantly, reduction of 2 was mediated by an NADPH-dependent cytosolic enzyme. Studies with human cytosolic fractions from multiple tissues, selective inhibitors, and recombinantly expressed enzymes indicated that carbonyl reductase 1 (CBR1) is responsible for this transformation in humans. Carbonyl reduction is emerging as an important pathway for endogenous and xenobiotic metabolism. With a lack of selective substrates and inhibitors to enable characterization of the involvement of CBR1, 2 could be a useful probe to assess CBR1 activity in vitro in both subcellular fractions and in cell-based systems.
Catalysts are substances that increase the reaction rate of a chemical reaction without being consumed in the process. Welcome to check out more blogs about 136-95-8, in my other articles. Formula: https://www.ambeed.com/products/136-95-8.html.
Reference:
1,8-Naphthyridine – Wikipedia,
,1,8-Naphthyridine | C8H6N2 – PubChem