The discovery of potent agonists for GPR88, an orphan GPCR, for the potential treatment of CNS disorders

Yingzhi Bi; Carolyn D Dzierba; Cynthia Fink; Yudith Garcia; Michael Green; Jianxin Han; Soojin Kwon; Godwin Kumi; Zhi Liang; Ying Liu; Ying Qiao; Yulian Zhang; Greg Zipp; Neil Burford; Meredith Ferrante; Robert Bertekap; Martin Lewis; Angela Cacace; Ryan S Westphal; David Kimball; Joanne J Bronson; John E Macor

doi:10.1016/j.bmcl.2015.02.038

The discovery of potent agonists for GPR88, an orphan GPCR, for the potential treatment of CNS disorders

Bioorg Med Chem Lett. 2015 Apr 1;25(7):1443-7. doi: 10.1016/j.bmcl.2015.02.038. Epub 2015 Feb 21.

Authors

Yingzhi Bi¹, Carolyn D Dzierba², Cynthia Fink¹, Yudith Garcia¹, Michael Green¹, Jianxin Han¹, Soojin Kwon¹, Godwin Kumi¹, Zhi Liang¹, Ying Liu¹, Ying Qiao¹, Yulian Zhang¹, Greg Zipp¹, Neil Burford², Meredith Ferrante², Robert Bertekap², Martin Lewis², Angela Cacace², Ryan S Westphal², David Kimball¹, Joanne J Bronson², John E Macor²

Affiliations

¹ Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
² Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.

PMID: 25754495
DOI: 10.1016/j.bmcl.2015.02.038

Abstract

Modulating GPR88 activity is suggested to have therapeutic utility in the treatment of CNS disorders, such as schizophrenia. This Letter will describe the discovery and SAR development of a class of potent GPR88 agonists.

Keywords: Agonists; CNS; GPC; GPR88; Schizophrenia.

MeSH terms

Amides / chemical synthesis
Amides / chemistry
Amides / pharmacology*
Amines / chemical synthesis
Amines / chemistry
Amines / pharmacology*
Central Nervous System Diseases / drug therapy*
Dose-Response Relationship, Drug
Drug Discovery*
Humans
Molecular Structure
Receptors, G-Protein-Coupled / agonists*
Structure-Activity Relationship

Substances

Amides
Amines
GPR88 protein, human
Receptors, G-Protein-Coupled