SCH-48461

SCH-48461
Names
Preferred IUPAC name
(3R,4S)-1,4-Bis(4-methoxyphenyl)-3-(3-phenylpropyl)azetidin-2-one
Identifiers
CAS Number
  • 148260-92-8 checkY
3D model (JSmol)
  • Interactive image
ChEMBL
  • ChEMBL23541 ☒N
ChemSpider
  • 117230 ☒N
PubChem CID
  • 132832
UNII
  • T0H910M40A checkY
CompTox Dashboard (EPA)
  • DTXSID50933354 Edit this at Wikidata
InChI
  • InChI=1S/C26H27NO3/c1-29-22-15-11-20(12-16-22)25-24(10-6-9-19-7-4-3-5-8-19)26(28)27(25)21-13-17-23(30-2)18-14-21/h3-5,7-8,11-18,24-25H,6,9-10H2,1-2H3/t24-,25-/m1/s1 ☒N
    Key: IMNTVVOUWFPRSB-JWQCQUIFSA-N ☒N
  • InChI=1/C26H27NO3/c1-29-22-15-11-20(12-16-22)25-24(10-6-9-19-7-4-3-5-8-19)26(28)27(25)21-13-17-23(30-2)18-14-21/h3-5,7-8,11-18,24-25H,6,9-10H2,1-2H3/t24-,25-/m1/s1
    Key: IMNTVVOUWFPRSB-JWQCQUIFBU
  • COc1ccc(cc1)[C@@H]2[C@H](C(=O)N2c3ccc(cc3)OC)CCCc4ccccc4
Properties
Chemical formula
 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).
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Infobox references
Chemical compound

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

  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. S2CID 30737100.
  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.
  • v
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Lipid-lowering agents (C10)
GI tract
Cholesterol absorption inhibitors, NPC1L1
Bile acid sequestrants/resins (LDL)
Liver
Statins (HMG-CoA reductase, LDL)
Niacin and derivatives (HDL and LDL)
MTTP inhibitors (VLDL)
ATP citrate lyase inhibitors (LDL)
Thyromimetics (VLDL)
Blood vessels
PPAR agonists (LDL)
Fibrates
Others
CETP inhibitors (HDL)
PCSK9 inhibitors (LDL)
ANGPTL3 inhibitors (LDL/HDL)
CombinationsOther


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