title: Structure activity relationship studies on chemically non-reactive glycine sulfonamide inhibitors of diacylglycerol lipase.
abstract: N-Benzylic-substituted glycine sulfonamides that reversibly inhibit diacylglycerol (DAG) lipases are reported. Detailed herein are the structure activity relationships, profiling characteristics and physico-chemical properties for the first reported series of DAG lipase (DAGL) inhibitors that function without covalent attachment to the enzyme. Highly potent examples are presented that represent valuable tool compounds for studying DAGL inhibition and constitute important leads for future medicinal chemistry efforts.
authors.affiliation: Discovery Chemistry, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: louis.chupak@bms.com.
authors.forename: Louis S
authors.initials: LS
authors.lastname: Chupak
authors.affiliation: Discovery Chemistry, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Discovery Chemistry, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Shuanghua
authors.initials: S
authors.lastname: Hu
authors.affiliation: Discovery Chemistry, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Discovery Chemistry, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.affiliation: Neuroscience Biology, Disease Sciences and Biologics, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lewis
authors.affiliation: Neuroscience Biology, Disease Sciences and Biologics, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Westphal
authors.affiliation: Lead Evaluation, Discovery, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Blat
authors.affiliation: Discovery Chemistry Platforms, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: McClure
authors.affiliation: Discovery Chemistry, Research and Development, Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gentles
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013449:Sulfonamides; D008071:Lipoprotein Lipase; D005998:Glycine
keywords: 2-Arachidonoylglycerol; Diacylglycerol; Endocannabinoid; Glycine; Lipase inhibitor; Sulfonamide