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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