737823-69-7Relevant academic research and scientific papers
Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema: Part 2
Inoue, Takayuki,Morita, Masataka,Tojo, Takashi,Nagashima, Akira,Moritomo, Ayako,Imai, Keisuke,Miyake, Hiroshi
, p. 2478 - 2494 (2013/06/26)
Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although our previous compound 1 showed potent VAP-1 inhibitory activity, the activity differed between humans and rats. This issue was overcome by a hybrid design using human VAP-1 specific inhibitor 2, which was found by high-throughput screening (HTS), a docking study of a human VAP-1 homology model, and an analysis of sequence information for humans and rats. As a result, we identified compound 35c, which showed strong VAP-1 inhibitory activity (human IC50 of 20 nM; rat IC50 of 72 nM) and significant inhibitory effects in the ex vivo test.
Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets
Baud, Matthias G. J.,Leiser, Thomas,Haus, Patricia,Samlal, Sharon,Wong, Ai Ching,Wood, Robert J.,Petrucci, Vanessa,Gunaratnam, Mekala,Hughes, Siobhan M.,Buluwela, Lakjaya,Turlais, Fabrice,Neidle, Stephen,Meyer-Almes, Franz-Josef,White, Andrew J. P.,Fuchter, Matthew J.
scheme or table, p. 1731 - 1750 (2012/04/23)
Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotoxicity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.
THIAZOLE DERIVATIVES AND THEIR USE AS VAP-1 INHIBITORS
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Page 79-80, (2010/02/07)
A compound of the formula (I): R1-NH-X-Y-Z (I) wherein R1 is acyl; X is a bivalent residue derived from optionally substituted thiazole; Y is a bond, lower alkylene or -COHN-; and Z is a groupe of the formulae (II) or (III) wherein R
