13990-07-3Relevant academic research and scientific papers
Design, synthesis characterization and in vitro biological activity of a series of 3-aryl-6-(bromoarylmethyl)-7H-thiazolo[3,2-b]-1, 2, 4-triazin-7-one derivatives as the novel acetylcholinesterase inhibitors
Xu, He Nan,Jin, Zhe,Liu, Si Jie,Liu, Hong Min,Li, Shuo,Lin, Huang Quan,Wan, David Chicheong,Hu, Chun
scheme or table, p. 765 - 768 (2012/09/22)
Bromination is used as a strategy to improve biological activity in medicinal chemistry. In order to study on the structure-activity relationships of the novel acetylcholinesterase inhibitors with 7H-thiazolo[3,2-b]-1, 2, 4-triazin-7-one scaffold, based o
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.
, 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.
2-OXO-1,2,4,5-TETRAHYDRO-1,3-BENZODIAZEPIN-3-YL-PIPERIDINES USED AS CGRP ANTAGONISTS
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Page/Page column 111, (2010/11/24)
The invention relates to novel CGRP antagonists of general formula (I), in which B, R1 and R2 are defined as cited in claim 1, to their tautomers, isomers, diastereomers, enantiomers, hydrates, mixtures and salts, in addition to the hydrates of their salts, in particular their physiologically compatible salts, with inorganic or organic acids or bases. The invention also relates to medicaments containing said compounds, to their use and to a method for their production.
CGRP ANTAGONISTS, METHOD FOR THE PRODUCTION THEREOF, AND THEIR USE AS MEDICAMENTS
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Page/Page column 106, (2008/06/13)
The invention relates to CGRP antagonists of general formula (I) in which: R1, R2, R3, R4 and X are defined as in Claim 1, to their tautomers, isomers, diastereomers, enantiomers, hydrates, mixtures and salts as well as the hydrates of the salts, in particular, their physiologically compatible salts with inorganic or organic acids and bases, and those compounds of general formula (I) in which one or more hydrogen atoms are replaced by deuterium. The invention also relates to medicaments containing these compounds, the use thereof, and to methods for producing them.
SELECTED CGRP ANTAGONISTS, METHODS FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICAMENTS
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Page/Page column 233, (2008/06/13)
The invention relates to CGRP antagonists of general formula (I), in which A, X, D, E, G, M, Q and R1 to R3 are defined as in Claim 1, to their tautomers, isomers, diastereomers, enantiomers, hydrates, mixtures and their salts as well as the hydrates of the salts, particularly their physiologically compatible salts having inorganic or organic acids, to medicaments containing these compounds, to their use, and to methods for the production thereof.
Synthesis of a bromotyrosine-derived natural product inhibitor of mycothiol-S-conjugate amidase
Fetterolf, Brandon,Bewley, Carole A.
, p. 3785 - 3788 (2007/10/03)
Recently we described the structures of two new bromotyrosine-derived alkaloids that inhibit the detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis. Here we describe a concise total synthesis of bromotyrosine oxime 1
Combinatorial synthesis through disulfide exchange: Discovery of potent psammaplin A type antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA)
Nicolaou,Hughes, Robert,Pfefferkorn, Jeffrey A.,Barluenga, Sofia,Roecker
, p. 4280 - 4295 (2007/10/03)
Psammaplin A is a symmetrical bromotyrosine-derived disulfide natural product isolated from the Psammaplysilla sponge, which exhibits in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the structure of this marine natural product, a combinatorial scrambling strategy for the construction of heterodimeric disulfide analogues was developed and applied to the construction of a 3828-membered library starting from 88 homodimeric disulfides. These psammaplin A analogues were screened directly against various gram positive bacterial strains leading to the discovery of a series of potent antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA). Among the most active leads derived from these studies are compounds 104, 105, 113, 115, 123, and 128. The present, catalytically-induced, disulfide exchange strategy may be extendable to other types of building blocks bearing thiol groups facilitating the construction of diverse discovery-oriented combinatorial libraries.
