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Partially Saturated Bicyclic Heteroaromatics as an sp 3 ‐Enriched Fragment Collection
Author(s) -
Twigg David G.,
Kondo Noriyasu,
Mitchell Sophie L.,
Galloway Warren R. J. D.,
Sore Hannah F.,
Madin Andrew,
Spring David R.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201606496
Subject(s) - stereocenter , bicyclic molecule , fragment (logic) , derivatization , chemistry , drug discovery , combinatorial chemistry , ring (chemistry) , stereochemistry , organic chemistry , computer science , catalysis , biochemistry , enantioselective synthesis , high performance liquid chromatography , programming language
Fragment‐based lead generation has proven to be an effective means of identifying high‐quality lead compounds for drug discovery programs. However, the fragment screening sets often used are principally comprised of sp 2 ‐rich aromatic compounds, which limits the structural (and hence biological) diversity of the library. Herein, we describe strategies for the synthesis of a series of partially saturated bicyclic heteroaromatic scaffolds with enhanced sp 3 character. Subsequent derivatization led to a fragment collection featuring regio‐ and stereo‐controlled introduction of substituents on the saturated ring system, often with formation of new stereocenters.