SCH-48461

From Wikipedia, the free encyclopedia
Jump to: navigation, search
SCH-48461
SCH-48461.svg
Names
IUPAC name
(3R,4S)-1,4-bis-(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone
Identifiers
3D model (Jmol)
ChemSpider
Properties
C26H27NO3
Molar mass 401.49748
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

SCH-48461 is a cholesterol absorption inhibitor.[1][2]

During the early phases of an NPC1L1 inhibitor discovery program at Schering-Plough, conformationally restricted analogs based on the 2-azetidinone backbone were targeted by Burnett and co-workers.[3] Early in the biological evaluation, it became apparent that even though the in vitro ACAT inhibitory activity of these analogs was modest (e.g., IC50 values of 2–50 mM), they exhibited significant activity in a cholesterol-fed hamster model (CFH). The discovery of the prototypical 2-azetidinone CAI, SCH-48461 (ACAT IC50 ~26 mM, ED50 of CE reduction in hamsters ~2.2 mpk) and the details of the first-generation SAR have been described in detail.[4]

References[edit]

  1. ^ Salisbury BG, Davis HR, Burrier RE, et al. (May 1995). "Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461". Atherosclerosis. 115 (1): 45–63. doi:10.1016/0021-9150(94)05499-9. PMID 7669087. 
  2. ^ Dujovne CA, Bays H, Davidson MH, et al. (January 2001). "Reduction of LDL cholesterol in patients with primary hypercholesterolemia by SCH 48461: results of a multicenter dose-ranging study". J Clin Pharmacol. 41 (1): 70–8. doi:10.1177/00912700122009854. PMID 11144997. 
  3. ^ Burnett, Duane A. (1994). "2-Azetidinones as Inhibitors of Cholesterol Absorption". Journal of Medicinal Chemistry. 37 (12): 1733–1736. doi:10.1021/jm00038a001. PMID 8021912. 
  4. ^ Clader, John W. (1996). "2-Azetidinone Cholesterol Absorption Inhibitors: Structure−Activity Relationships on the Heterocyclic Nucleus". Journal of Medicinal Chemistry. 39 (19): 3684–3693. doi:10.1021/jm960405n. PMID 8809157.