- Conde-Ceide S, Martínez-Viturro CM, Alcázar J, Garcia-Barrantes PM, Lavreysen H, Mackie C, Vinson PN, Rook JM, Bridges TM, Daniels JS, Megens A, Langlois X, Drinkenburg WH, Ahnaou A, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Bartolomé-Nebreda JM, Lindsley CW. Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS medicinal chemistry letters. 2015 Jun 11;6(6). 716-20. PMID: 26157544 [PubMed]. PMCID: PMC4492464.
Herein, we report the structure-activity relationship of a novel series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones as potent, selective, and orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu5) positive allosteric modulators (PAMs). On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, 17a (VU0409551/JNJ-46778212) was selected as a candidate for further development.