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Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1.

ABSTRACT: Amalgamation of the structure-activity relationship of two series of GlyT1 inhibitors developed at Merck led to the discovery of a clinical candidate, compound 16 (DCCCyB), which demonstrated excellent in vivo occupancy of GlyT1 transporters in rhesus monkey as determined by displacement of a PET tracer ligand.

SUBMITTER: Blackaby WP

PROVIDER: S-EPMC4007840 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1.

Blackaby Wesley P WP Lewis Richard T RT Thomson Joanne L JL Jennings Andrew S R AS Goodacre Simon C SC Street Leslie J LJ MacLeod Angus M AM Pike Andrew A Wood Suzanne S Thomas Steve S Brown Terry A TA Smith Alison A Pillai Gopalan G Almond Sarah S Guscott Martin R MR Burns H Donald HD Eng Waisi W Ryan Christine C Cook Jacquelynn J Hamill Terence G TG

ACS medicinal chemistry letters 20100625 7

Amalgamation of the structure-activity relationship of two series of GlyT1 inhibitors developed at Merck led to the discovery of a clinical candidate, compound 16 (DCCCyB), which demonstrated excellent in vivo occupancy of GlyT1 transporters in rhesus monkey as determined by displacement of a PET tracer ligand. ...[more]

PMID: 24900218

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