23269-55-8Relevant academic research and scientific papers
5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma
Kahl, Dylan J.,Hutchings, Kim M.,Lisabeth, Erika Mathes,Haak, Andrew J.,Leipprandt, Jeffrey R.,Dexheimer, Thomas,Khanna, Dinesh,Tsou, Pei-Suen,Campbell, Phillip L.,Fox, David A.,Wen, Bo,Sun, Duxin,Bailie, Marc,Neubig, Richard R.,Larsen, Scott D.
, p. 4350 - 4369 (2019/05/08)
Through a phenotypic high-throughput screen using a serum response element luciferase promoter, we identified a novel 5-aryl-1,3,4-oxadiazol-2-ylthiopropionic acid lead inhibitor of Rho/myocardin-related transcription factor (MRTF)/serum response factor (SRF)-mediated gene transcription with good potency (IC50 = 180 nM). We were able to rapidly improve the cellular potency by 5 orders of magnitude guided by sharply defined and synergistic SAR. The remarkable potency and depth of the SAR, as well as the relatively low molecular weight of the series, suggests, but does not prove, that binding to the unknown molecular target may be occurring through a covalent mechanism. The series nevertheless has no observable cytotoxicity up to 100 μM. Ensuing pharmacokinetic optimization resulted in the development of two potent and orally bioavailable anti-fibrotic agents that were capable of dose-dependently reducing connective tissue growth factor gene expression in vitro as well as significantly reducing the development of bleomycin-induced dermal fibrosis in mice in vivo.
Direction of alkylation of 5-aryl-1,3,4-oxadiazoline-2-thiones
Ziyaev,Galust'yan
, p. 1109 - 1111 (2007/10/03)
The reaction of potassium salt of 5-(2,4-dichlorophenyl)-1,3,4-oxadiazoline-2-thione with dimethyl sulfate was carried out in water and HMPT. It was shown that the nature of the solvent affects the ratio of the formed products of S- and N-methylation. The alkylation of 5-aryl-1,3,4-oxadiazoline-2-thiones with isomeric butyl chlorides showed that the reaction takes place only with n-butyl chloride with the formation of the corresponding S-butyl-substituted derivative. 1998 Plenum Publishing Corporation.
METHYLATION OF 5-ARYL-1,3,4-OXADIAZOLINE-2-THIONES
Ziyaev, A. A.,Galust'yan, G. G.,Sabirov, K.,Nasirov, S.,Tashkhodzhaev, B.,Yagudaev, M. R.
, p. 1221 - 1225 (2007/10/02)
The methylation of 5-aryl-1,3,4-oxadiazoline-2-thiones in various solvents in the range of 56-81 deg C leads to the formation of S-methyl derivatives and to insignificant formation of N-methyl derivatives.
