Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
|what is: / ?)(|
During the early phases of an ACAT inhibitor discovery program at Schering-Plough, conformationally restricted analogs based on the 2-azetidinone backbone were targeted by Burnett and co-workers. 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.
SCH-48461 reduced LDL-C by –13% at a daily dose of 25 mg.
- 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.
- 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.
- Burnett, Duane A. (1994). "2-Azetidinones as Inhibitors of Cholesterol Absorption". Journal of Medicinal Chemistry 37 (12): 1733–1736. doi:10.1021/jm00038a001.
- 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.
|This drug article relating to the cardiovascular system is a stub. You can help Wikipedia by expanding it.|