Partially Saturated Bicyclic Heteroaromatics as an sp(3) -Enriched Fragment Collection.
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.
Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.
David G
DG
Twigg
Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.|Shionogi & Co. Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan.
Noriyasu
N
Kondo
Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.
Sophie L
SL
Mitchell
Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.
Warren R J D
WR
Galloway
Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.
Hannah F
HF
Sore
AstraZeneca UK Ltd., 310 Cambridge Science Park, Milton Rd, Cambridge, CB4 0FZ, UK.
Andrew
A
Madin
Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK. spring@ch.cam.ac.uk.
David R
DR
Spring
drug design; drug discovery; fused-ring systems; nitrogen heterocycles; synthetic methods