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

  • ACS Med Chem Lett. 2010 Jun 25;1(7):350-4. doi: 10.1021/ml1001085.
Wesley P Blackaby  1 Richard T Lewis  1 Joanne L Thomson  1 Andrew S R Jennings  1 Simon C Goodacre  1 Leslie J Street  1 Angus M MacLeod  1 Andrew Pike  1 Suzanne Wood  1 Steve Thomas  1 Terry A Brown  1 Alison Smith  1 Gopalan Pillai  1 Sarah Almond  1 Martin R Guscott  1 H Donald Burns  2 Waisi Eng  2 Christine Ryan  2 Jacquelynn Cook  2 Terence G Hamill  2
Affiliations
  • 1. Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
  • 2. Research Imaging, Merck Research Laboratories, West Point, Pennsylvania 19486.
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.

Keywords
DCCCyB; GlyT1; Inhibitor; PET tracer ligand; structure−activity relationship.
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