Description: BMS-986163, a novel water-soluble phosphate prodrug of BMS-986169 designed for IV administration, is a negative allosteric modulator of GluN2B which is a N-methyl-d-aspartate receptor subtype. The prodrug BMS-986163 can be rapidly convertd to its active form BMS-986169 which has Ki of 4 nM and IC50 of 24 nM. BMS-986163 has potential to be used in major depressive disorder. BMS-986169 exhibited high binding affinity for the GluN2B allosteric site (Ki = 4.0 nM) and selective inhibition of GluN2B receptor function (IC50 = 24 nM) in cells. The conversion of prodrug BMS-986163 to parent BMS-986169 was rapid in vitro and in vivo across preclinical species. The prodrug BMS-986163 has demonstrated an acceptable safety and toxicology profile and was selected as a preclinical candidate for further evaluation in major depressive disorder.