1055304-08-9Relevant academic research and scientific papers
Mining Natural Products for Macrocycles to Drug Difficult Targets
Begnini, Fabio,Poongavanam, Vasanthanathan,Over, Bj?rn,Castaldo, Marie,Geschwindner, Stefan,Johansson, Patrik,Tyagi, Mohit,Tyrchan, Christian,Wissler, Lisa,Sj?, Peter,Schiesser, Stefan,Kihlberg, Jan
, p. 1054 - 1072 (2021)
Lead generation for difficult-to-drug targets that have large, featureless, and highly lipophilic or highly polar and/or flexible binding sites is highly challenging. Here, we describe how cores of macrocyclic natural products can serve as a high-quality in silico screening library that provides leads for difficult-to-drug targets. Two iterative rounds of docking of a carefully selected set of natural-product-derived cores led to the discovery of an uncharged macrocyclic inhibitor of the Keap1-Nrf2 protein-protein interaction, a particularly challenging target due to its highly polar binding site. The inhibitor displays cellular efficacy and is well-positioned for further optimization based on the structure of its complex with Keap1 and synthetic access. We believe that our work will spur interest in using macrocyclic cores for in silico-based lead generation and also inspire the design of future macrocycle screening collections.
2 -SUBSTITUTED- 3 -PHENYLPROPIONIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE
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Page/Page column 72, (2008/12/08)
The present invention relates to 2-(substituted sulphur, sulphone or sulphoxide)-3-(substituted phenyl) propionic acid derivatives, 2-(substituted oxygen)-3-(substituted phenyl) propionic acid derivatives, benzoic acid derivatives, and derivatives of 2-methyl-2-(phenoxy or phenylthio)propanoic acid and 2-(methylor ethyl)-2-(phenoxy or phenylthio)butanoic acid, to processes for preparing such compounds, to their use in the treatment of inflammatory conditions, and to pharmaceutical compositions containing them.
