125972-75-0Relevant academic research and scientific papers
Structural basis for potent inhibition of D-amino acid oxidase by thiophene carboxylic acids
Kato, Yusuke,Hin, Niyada,Maita, Nobuo,Thomas, Ajit G.,Kurosawa, Sumire,Rojas, Camilo,Yorita, Kazuko,Slusher, Barbara S.,Fukui, Kiyoshi,Tsukamoto, Takashi
, p. 23 - 34 (2018)
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. Molecular dynamics simulations of the complex revealed that Tyr224 preferred the stacked conformation irrespective 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.
Palladacycle-catalyzed deacetonative sonogashira coupling of aryl propargyl alcohols with aryl chlorides
Hu, Hao,Yang, Fan,Wu, Yangjie
, p. 10506 - 10511 (2013/11/06)
An efficient and general protocol for the deacetonative Sonogashira coupling of aryl propargyl alcohols with aryl chlorides is described. The reaction proceeded smoothly with the catalyst system of palladacycle/Xphos. This result represents the first succ
Photochemical Reactivity of Halofuran and Halothiophene Derivatives in the Presence of Arylalkenes and Arylalkynes
D'Auria, Maurizio,Piancatelli, Giovanni,Ferri, Tommaso
, p. 4019 - 4025 (2007/10/02)
The photochemical reactions of 5-iodothiophene-2-carbaldehyde (4a), 2-acetyl-5-iodothiophene (4b), 5-bromofuran-2-carbaldehyde (3b) with arylalkenes 5 (styrene), 7 (2-vinylthiophene), 10 (2-vinylfuran), 12 (4-methyl-5-vinylthiazole), and 16 (benzofuran) are reported.All of the reactions give the corresponding substitution products as a cis-trans mixture.The photochemical reaction of 4a and 4c (methyl 5-iodothiophene-2-carboxylate) with arylalkynes is also reported: in this case the reaction of 4a and 4c with phenylacetylene (18) furnishes the substitution products (19 and 26, respectively) deriving from an attack on the alkyne moiety, while the reaction with 2-ethynylthiophene (20) and 2-ethynylfuran (23) furnishes a mixture deriving from the attack both on the alkyne and on the heterocyclic ring.The ratio between these two products can be modified by changing the concentrations of the reagents.The mechanism of these reactions is discussed on the basis of photochemical and electrochemical properties of the reagents in terms of an electron-transfer process.The experimental results are explained in terms of ΔG values, and they are in agreement with the formation of both a solvent-separated pair and a contact radical ion pair.
