title: A 2-methyleneoxetane analog of orlistat demonstrating inhibition of porcine pancreatic lipase.
abstract: The 2-methyleneoxetane analog 2 of orlistat (OLS, 1) has been synthesized and tested against porcine pancreatic lipase (PPL). Despite the loss of the carbonyl group, a potential site for hydrogen bonding interaction with the enzyme and the key element in the acylation by OLS, 2 has activity comparable to 1.
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs 06269-4060, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Dollinger
authors.forename: A R
authors.initials: AR
authors.lastname: Howell
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D015394:Molecular Structure; D000077403:Orlistat; D010179:Pancreas / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D006573:Heterocyclic Compounds, 1-Ring; D007783:Lactones; C116631:N-formyl-1-((3-hexyl-4-methylene-2-oxetanyl)methyl)dodecyl 2-amino-4-methylpentanoate; D000077403:Orlistat; D008049:Lipase; D007930:Leucine