299953-06-3

A series of 2-amino-5-arylmethyl- or 5-heteroarylmethyl-1,3-thiazole derivatives were synthesized and evaluated for BK channel-opening activities in cell-based fluorescence assay and electrophysiological recording. The assay results indicated that the activities of the investigated compounds were influenced by the physicochemical properties of the substituent at benzene ring.

Aim. Synthesis of a series of new N-(5-benzyl-thiazol-2-yl)-2-(heteryl-5-ylsulfanyl)-acetamides and study of their anticancer activity. Methods. Organic synthesis, analytical and spectral methods, pharmacological screening. Results. [2-chloro-N-(5-aryl-1,

Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 (hSirt2) activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, which makes the modulation of hSirt2 activity a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently been discovered by us as highly potent and isotype-selective hSirt2 inhibitors. Here, we present a well-defined structure-activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the hSirt2 targeted tubulin caused by our improved lead structure.

Compounds represented by the formula (I) or pharmaceutically acceptable salts thereof: [in-line-formulae]R2—Y—Z-Q-A-R1??Formula (I)[/in-line-formulae] wherein R1, R2, Y, Z, Q, and A are as defined. These compoun

A new chemical series was identified via high-throughput screening as having antiproliferative activity on DU-145 human prostate carcinoma cell line (hit compound potency - 2.9 μM). Medicinal chemistry optimization of two peripheral diversity vectors of t

Generation of imino-quinone methide type intermediates from 2-aminothiazole-5-carbinols using alkylsulfonic acids in nitromethane followed by trapping with a wide range of nucleophiles effects C-C, C-O, C-N, C-S, and C-P bond formation

Meerwein reaction of arenediazonium chlorides with acrolein gave 3-aryl-2-chloropropanals which were brought into cyclocondensation with thiourea. The resulting 2-amino-5-benzyl-1,3-thiazoles were acylated with carboxylic acid chlorides and phthalic anhydride to afford, respectively, 2-acylamino-5-benzyl-1,3-thiazoles and N-(5-benzyl-1,3-thiazol-2-yl) phthalimides.