Category: 74598-03-1

Clarke, Kenneth published the artcileCondensed isothiazoles. Part 5. Thieno[2,3-d]isothiazoles and thien[3,2-d]isothiazoles, Related Products of chlorides-buliding-blocks, the main research area is thienoisothiazole; mercaptothiophenecarbaldoxime cyclization; thiophenecarbaldoxime mercapto cyclization; cyclocondensation mercaptothienyl ketone chloramine; thienooxathiazepine ring contraction thienoisothiazole.

The title compounds were prepared from 2,3-disubstituted thiophenes containing a S function (SH, SMe, or SCN) and a CO group (CHO or Ac). E.g., heating the (E)-mercaptothiophenecarbaldoxime I (R = CO2Et, R1 = H, R2 = CH:NOH, R3 = SH) in DMSO at 170° gave 74% Et thieno[3,2-d]isothiazole-5-carboxylate (II). The (E)-mercaptothiophenecarbaldoxime I (R = Me, R1 = CO2Et, R2 = SH, R3 = CH:NOH) cyclized in boiling AcOH-Ac2O in 5 min to give 79% of the thieno[2,3-d]isothiazolecarboxylate III. Thieno[3,2-d]isothiazoles were also prepared by treating a Me (2-mercapto-3-thienyl) ketone with chloramine and by heating a 2-iminothieno[3,2-d]-3,1,4-oxathiazepine in an inert solvent. The products obtained by selective S-alkylation of 3,5-bis(sodiomercapto)isothiazole-4-carbonitrile with BrCH2CO2Et and MeI were cyclized to give 4-aminothieno[3,2-d or 2,3-c]isothiazoles.

Journal of the Chemical Society, Perkin Transactions 4: Organic and Bio-Organic Chemistry published new progress about Cyclization. 74598-03-1 belongs to class chlorides-buliding-blocks, name is 5-Chloro-4-methylthiophene carboxylic acid, and the molecular formula is C6H5ClO2S, Related Products of chlorides-buliding-blocks.

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

Kato, Yusuke published the artcileStructural basis for potent inhibition of D-amino acid oxidase by thiophene carboxylic acids, Category: chlorides-buliding-blocks, the main research area is thiophene carboxylate inhibitor amino acid oxidase DAO crystal structure; Drug discovery; Flavoenzyme; Molecular dynamics; Schizophrenia; X-ray crystallography.

A series of thiophene-2-carboxylic acids and thiophene-3-carboxylic acids were identified as a new class of DAO inhibitors. Structure-activity relationship (SAR) studies revealed that small substituents are well-tolerated on the thiophene ring of both the 2-carboxylic acid and 3-carboxylic acid scaffolds. Crystal structures of human DAO in complex with potent thiophene carboxylic acids revealed that Tyr224 was tightly stacked with the thiophene ring of the inhibitors, resulting in the disappearance of the secondary pocket observed with other DAO inhibitors. Mol. dynamics simulations of the complex revealed that Tyr224 preferred the stacked conformation irresp. of whether Tyr224 was stacked or not in the initial state of the simulations. MM/GBSA indicated a substantial hydrophobic interaction between Tyr244 and the thiophene-based inhibitor. In addition, the active site was tightly closed with an extensive network of hydrogen bonds including those from Tyr224 in the stacked conformation. The introduction of a large branched side chain to the thiophene ring markedly decreased potency. These results are in marked contrast to other DAO inhibitors that can gain potency with a branched side chain extending to the secondary pocket due to Tyr224 repositioning. These insights should be of particular importance in future efforts to optimize DAO inhibitors with novel scaffolds.

European Journal of Medicinal Chemistry published new progress about Conformational transition. 74598-03-1 belongs to class chlorides-buliding-blocks, name is 5-Chloro-4-methylthiophene carboxylic acid, and the molecular formula is C6H5ClO2S, Category: chlorides-buliding-blocks.

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