2. Academic Validation
  3. Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1

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

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.
PMID: 24900218 DOI: 10.1021/ml1001085
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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