Category: 39489-79-7

The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity was written by Newton, Rebecca;Bowler, Katherine A.;Burns, Emily M.;Chapman, Philip J.;Fairweather, Emma E.;Fritzl, Samantha J. R.;Goldberg, Kristin M.;Hamilton, Niall M.;Holt, Sarah V.;Hopkins, Gemma V.;Jones, Stuart D.;Jordan, Allan M.;Lyons, Amanda J.;Nikki March, H.;McDonald, Neil Q.;Maguire, Laura A.;Mould, Daniel P.;Purkiss, Andrew G.;Small, Helen F.;Stowell, Alexandra I. J.;Thomson, Graeme J.;Waddell, Ian D.;Waszkowycz, Bohdan;Watson, Amanda J.;Ogilvie, Donald J.. And the article was included in European Journal of Medicinal Chemistry in 2016.Recommanded Product: 5-Amino-2,4-dichlorophenol This article mentions the following:

Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clin. approved multi-kinase inhibitors that target RET as a secondary pharmacol. but addnl. activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clin. need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR. In the experiment, the researchers used many compounds, for example, 5-Amino-2,4-dichlorophenol (cas: 39489-79-7Recommanded Product: 5-Amino-2,4-dichlorophenol).

5-Amino-2,4-dichlorophenol (cas: 39489-79-7) belongs to organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Recommanded Product: 5-Amino-2,4-dichlorophenol

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Metabolism of 2,4-, 2,5-, and 3,4-dichloronitrobenzene in the rabbit was written by Bray, H. G.;James, Sybil P.;Thorpe, W. V.. And the article was included in Biochemical Journal in 1957.Application In Synthesis of 5-Amino-2,4-dichlorophenol This article mentions the following:

The metabolism of 2,4-, 2,5-, and 3,4-dichloronitrobenzene has been studied in the rabbit. The main products excreted in urine are mercapturic acids (corresponding to 30-50% of the dose) and phenols conjugated with glucuronic and sulfuric acids. Smaller amounts of dichloroanilines are excreted. The mercapturic acids have been isolated and their structure has been confirmed by synthesis. In each case they are formed by substitution of the labile Cl. 2-Bromo-4-chloro-, 2-bromo-5-chloro-, and 4-bromo-3-chloronitrobenzene when fed to rabbits yield the same mercapturic acids as do the corresponding dichloronitrobenzenes. The following nitro- and aminodichlorophenols excreted have been identified: N-acetyl-S-(5-chloro-2-nitrophenyl)-L-cysteine, m. 192°, [α]_D²⁰ in EtOH + 63 ± 3°, absorption maximum 253 mμ, 375, N-acetyl-S-(4-chloro-2-nitrophenyl)-L-cysteine 161-2, 104 ± 7, 249, 390; N-acetyl-S-(2-chloro-4-nitrophenyl)-L-cysteine 192-194, -4 ± 4, 345; 2,4-, 2,5- and 3,4-dichloroaniline, 2,4-dichloro-5-nitrophenol, 3,5-dichloro-2-nitrophenol, 2-amino-3,5-dichlorophenol, 3-amino-2,6-dichlorophenol, 5-amino-2,4-dichlorophenol, 2,5-dichloro-4-nitrophenol, 3-amino-2,5-dichlorophenol, 4-amino-2,5-dichlorophenol, 2-aminodichlorophenol, 5-amino-2,3-dichlorophenol. R_f values in 3 solvents have been determined for the various possible metabolites of the dichloronitrobenzenes. 3,3′,4,4′-Tetrachloroazoxybenzene has been isolated from the urine of rabbits given 3,4-dichloronitrobenzene. The difference between the metabolic fates of the dichloronitrobenzenes and those of the monochloronitrobenzenes are discussed. Mercapturic acid formation provides the major metabolite pathway for the dichloro compounds and hydroxylation is the principal metabolite process for the monochloro compounds In the experiment, the researchers used many compounds, for example, 5-Amino-2,4-dichlorophenol (cas: 39489-79-7Application In Synthesis of 5-Amino-2,4-dichlorophenol).

5-Amino-2,4-dichlorophenol (cas: 39489-79-7) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Organochlorine compounds are lipophylic, meaning they are more soluble in fat than in water. This gives them a high tenancy to accumulate in the food chain (biomagnification).Application In Synthesis of 5-Amino-2,4-dichlorophenol

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics