ChemInform Abstract: Novel, One‐Pot Procedure for the Synthesis of 2‐Arylethanol Derivatives.

Schlaeger, Torsten; Oberdorf, Christoph; Tewes, Bastian; Wuensch, B.

doi:10.1002/chin.200841077

Cited by 1 publication

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“…Dihydropyrrolopyrimidines (DHPPs) were prepared according to Scheme . Reaction of 1,3,2-dioxathiolane 2,2-dioxide ( 21 ) with 2-morpholino-4,6-dichloropyrimidine ( 20 ) in the presence of n -butyllithium furnished 22 , which then underwent an SNAr reaction with aminopyrrolidine 23 . Subsequent mesylation of 24 and base-mediated ring closure provided the DHPP scaffold 25 .…”

Section: Resultsmentioning

confidence: 99%

Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195)

et al. 2020

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The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A PI3Kα-selective inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a PI3Kα-selective inhibitor by applying structure-based drug design (SBDD) and computational analysis. A novel series of compounds, exemplified by 2,2-difluoroethyl (3S)-3-{[2′-amino-5-fluoro-2-(morpholin-4-yl)-4,5′-bipyrimidin-6-yl]amino}-3-(hydroxymethyl)pyrrolidine-1-carboxylate (1) (PF-06843195), with high PI3Kα potency and unique PI3K isoform and mTOR selectivity were discovered. We describe here the details of the design and synthesis program that lead to the discovery of 1.

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Section: Resultsmentioning

confidence: 99%