Optimization of Potency and Pharmacokinetic Properties of Tetrahydroisoquinoline Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists was written by Horne, Daniel B.;Tamayo, Nuria A.;Bartberger, Michael D.;Bo, Yunxin;Clarine, Jeffrey;Davis, Carl D.;Gore, Vijay K.;Kaller, Matthew R.;Lehto, Sonya G.;Ma, Vu V.;Nishimura, Nobuko;Nguyen, Thomas T.;Tang, Phi;Wang, Weiya;Youngblood, Beth D.;Zhang, Maosheng;Gavva, Narender R.;Monenschein, Holger;Norman, Mark H.. And the article was included in Journal of Medicinal Chemistry in 2014.Recommanded Product: 16413-26-6 This article mentions the following:
Trifluoromethylaryl-substituted tetrahydroisoquinolinecarboxamides, tetrahydronaphthyridinecarboxamides, a tetrahydropyridopyrimidinecarboxamide, and a tetrahydropyridopyrazinecarboxamide such as tetrahydronaphthyridinecarboxamide I were prepared as inhibitors of the transient receptor potential melastatin 8 (TRPM8) cation channel, the predominant mammalian thermosensor for both temperature- and cooling agent-induced sensations in a subpopulation of peripheral sensory neurons, for potential use in the treatment of pain and bladder disorders. The inhibition of human and rat TRPM8 cation channels by the compounds and their degradation by liver microsomes were determined; for I and three other compounds, the oral and i.v. pharmacokinetics were determined in rats. I demonstrated robust efficacy at inhibiting the response of TRPM8 to cooling agents (icilin) and cold temperatures in rats with ED90 values <3 mg/kg. Trifluoromethylaryl Grignard reagents used for the preparation of some of the title compounds have been found to decompose very exothermically and should be prepared and used with caution. In the experiment, the researchers used many compounds, for example, 3-Cyanophenylisocyanate (cas: 16413-26-6Recommanded Product: 16413-26-6).
3-Cyanophenylisocyanate (cas: 16413-26-6) belongs to esters. Esters are also usually derived from carboxylic acids. It may also be obtained by reaction of acid anhydride or acid halides with alcohols or by the reaction of salts of carboxylic acids with alkyl halides. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Recommanded Product: 16413-26-6
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics