92646-75-8Relevant academic research and scientific papers
Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity
Mahy, William,Patel, Mikesh,Steadman, David,Woodward, Hannah L.,Atkinson, Benjamin N.,Svensson, Fredrik,Willis, Nicky J.,Flint, Alister,Papatheodorou, Dimitra,Zhao, Yuguang,Vecchia, Luca,Ruza, Reinis R.,Hillier, James,Frew, Sarah,Monaghan, Amy,Costa, Artur,Bictash, Magda,Walter, Magnus W.,Jones, E. Yvonne,Fish, Paul V.
, p. 9464 - 9483 (2020/10/19)
The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles.
An efficient and convenient synthesis of 1,2,3-trisubstituted pyrroles via iodocyclization from ethyl acetoacetate
Xu, Pengfei,Huang, Kunzhu,Liu, Zhiguo,Zhou, Ming,Zeng, Wenbin
supporting information, p. 2929 - 2933 (2013/06/27)
A novel and efficient methodology for the synthesis of 1,2,3-trisubstituted pyrroles by one-pot two-step reaction has been developed. The iodocyclization of a series of β-enamino esters followed by dehydroiodination, led to the formation of corresponding pyrroles. This approach provides an easy access to a wide range of 1,2,3-trisubstituted pyrroles.
PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS, AND METHODS OF USE THEREOF
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Page/Page column 24, (2008/06/13)
The present invention relates to novel compounds capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).
A two step synthesis of 1,2,3-substituted pyrroles
Cunha, Anna C.,Pereira, Leticia O. R.,De Souza, Rodrigo O. P.,De Souza, Maria Cecilia B. V.,Ferreira, Vitor F.
, p. 3215 - 3226 (2007/10/03)
A method for preparing substituted pyrroles 3a-g in two steps from dihydrofurans 2a-b which were synthesized from α,α'-diazocarbonyl derivatives 1a-b was developed. The relevance of this research work lies in the easiness of preparing the substituted dihydrofurans and transforming them into pyrroles under mild conditions.
Unsaturated Sulfoxides in Organic Synthesis: a New General Pyrrole Synthesis
Chan, Wing Hong,Lee, Albert W. M.,Lee, Ka Ming,Lee, Tin Yau
, p. 2355 - 2356 (2007/10/02)
Pyrroles have been efficiently synthesised by a three-step reaction sequence.Michael addition of keto esters onto phenyl vinyl sulfoxide followed by Pummerer rearrangement gave the cyclic key intermediate 3.Mercury(II) salt induced carbon-sulfur bond clea
