Prospective exploration of synthetically feasible, medicinally relevant chemical space.
We describe a novel approach to direct the exploration of chemical space in an effort to balance synthetic accessibility and medicinal relevancy prior to experimental work. Reaction transforms containing empirical reactivity and compatibility information are dynamically assembled into reaction sequences (vProtocols) utilizing commercially available starting material feedstock. These vProtocols are evolved and optimized by a genetic algorithm, which leverages fitness functions based on predicted properties of generated molecular products. We present the underlying concepts, methodology and initial results of this prospective approach.
Schürer
Stephan C
SC
Sertanty, Inc., 9381 Judicial Drive, Suite 200, San Diego, California 92121, USA.
Tyagi
Prashant
P
Muskal
Steven M
SM
D000465:Algorithms; D003198:Computer Simulation; D015195:Drug Design; D005240:Feasibility Studies; D006358:Hot Temperature; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14