SCH-48461

SCH-48461

Names
IUPAC name (3R,4S)-1,4-bis-(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone
Identifiers
CAS Number	148260-92-8
3D model (Jmol)	Interactive image
ChEMBL	ChEMBL23541
ChemSpider	117230
PubChem	132832
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 Key: IMNTVVOUWFPRSB-JWQCQUIFSA-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
SMILES 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

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.
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.