Synthesis and reactivity of 3-amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones: development of a novel kinase-focussed library

3-Amino-1H-pyrazolo4,3-c]pyridin-4(5H)-ones represent a potentially attractive heteroaromatic scaffold for drug-discovery chemistry. In particular, the arrangement of hydrogen bond donor and acceptor groups in the bicyclic core can fulfil the requirements for ATP competitive binding to kinase enzymes. Efficient and regioselective routes from simple starting materials to novel functionalised 3-amino-1H-pyrazolo4,3-c]pyridin-4(5H)-ones and related 3-amino-2H-pyrazolo4,3-c]pyridines were explored and adapted for parallel synthesis, resulting in a library of compounds suitable for screening against kinases and other cancer drug targets. Methods for substituent variation at five distinct positions around the bicyclic core were devised to generate sets of compounds containing two- or three-point diversity.