A 2-methyleneoxetane analog of orlistat demonstrating inhibition of porcine pancreatic lipase

Bioorg Med Chem Lett. 1998 Apr 21;8(8):977-8. doi: 10.1016/s0960-894x(98)00140-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Ethers, Cyclic / chemical synthesis*
  • Ethers, Cyclic / chemistry
  • Ethers, Cyclic / pharmacology
  • Heterocyclic Compounds, 1-Ring / chemical synthesis*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Lactones / chemical synthesis*
  • Lactones / chemistry*
  • Lactones / pharmacology
  • Leucine / analogs & derivatives*
  • Leucine / chemical synthesis
  • Leucine / chemistry
  • Leucine / pharmacology
  • Lipase / antagonists & inhibitors*
  • Molecular Conformation
  • Molecular Structure
  • Orlistat
  • Pancreas / enzymology*
  • Structure-Activity Relationship
  • Swine

Substances

  • Enzyme Inhibitors
  • Ethers, Cyclic
  • Heterocyclic Compounds, 1-Ring
  • Lactones
  • N-formyl-1-((3-hexyl-4-methylene-2-oxetanyl)methyl)dodecyl 2-amino-4-methylpentanoate
  • Orlistat
  • Lipase
  • Leucine