title: The discovery of potent agonists for GPR88, an orphan GPCR, for the potential treatment of CNS disorders.
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.
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Dzierba
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fink
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Yudith
authors.initials: Y
authors.lastname: Garcia
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Han
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Soojin
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Godwin
authors.initials: G
authors.lastname: Kumi
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Greg
authors.initials: G
authors.lastname: Zipp
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Burford
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Meredith
authors.initials: M
authors.lastname: Ferrante
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Bertekap
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Lewis
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Cacace
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Westphal
authors.affiliation: Lexicon Pharmaceuticals, Inc., 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: David
authors.initials: D
authors.lastname: Kimball
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Joanne J
authors.initials: JJ
authors.lastname: Bronson
authors.affiliation: Discovery, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000588:Amines; C418740:GPR88 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Agonists; CNS; GPC; GPR88; Schizophrenia