Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis was written by Ruminski, Peter G.;Massa, Mark;Strohbach, Joseph;Hanau, Cathleen E.;Schmidt, Michelle;Scholten, Jeffrey A.;Fletcher, Theresa R.;Hamper, Bruce C.;Carroll, Jeffery N.;Shieh, Huey S.;Caspers, Nicole;Collins, Brandon;Grapperhaus, Margaret;Palmquist, Katherine E.;Collins, Joe;Baldus, John E.;Hitchcock, Jeffrey;Kleine, H. Peter;Rogers, Michael D.;McDonald, Joseph;Munie, Grace E.;Messing, Dean M.;Portolan, Silvia;Whiteley, Laurence O.;Sunyer, Teresa;Schnute, Mark E.. And the article was included in Journal of Medicinal Chemistry in 2016.Recommanded Product: 223131-01-9 This article mentions the following:
Matrix metalloproteinase-13 (MMP-13) is a zinc-dependent protease responsible for the cleavage of type II collagen, the major structural protein of articular cartilage. Degradation of this cartilage matrix leads to the development of osteoarthritis. We previously have described highly potent and selective carboxylic acid containing MMP-13 inhibitors; however, nephrotoxicity in preclin. toxicol. species precluded development. The accumulation of compound in the kidneys mediated by human organic anion transporter 3 (hOAT3) was hypothesized as a contributing factor for the finding. Herein we report our efforts to optimize the MMP-13 potency and pharmacokinetic properties of non-carboxylic acid leads resulting in the identification of compound 43a lacking the previously observed preclin. toxicol. at comparable exposures. In the experiment, the researchers used many compounds, for example, tert-Butyl (cis-4-(hydroxymethyl)cyclohexyl)carbamate (cas: 223131-01-9Recommanded Product: 223131-01-9).
tert-Butyl (cis-4-(hydroxymethyl)cyclohexyl)carbamate (cas: 223131-01-9) belongs to alcohols. The oxygen atom of the strongly polarized O―H bond of an alcohol pulls electron density away from the hydrogen atom. This polarized hydrogen, which bears a partial positive charge, can form a hydrogen bond with a pair of nonbonding electrons on another oxygen atom. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Recommanded Product: 223131-01-9
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts