Biomedical subjects
Publications and source records attributed to C Q Meng.
A series of nitrobenzene compounds has been discovered as potent inhibitors of VCAM-1 expression and, therefore, potential drug candidates for autoimmune and allergic inflammatory diseases. Structure-activity relationship (SAR) studies showed that a nitro group and two other electron-withdrawing groups are essential for these compounds to be potent inhibitors of VCAM-1 expression.
Ezetimibe (Sch-58235) is a cholesterol absorption inhibitor being developed by Schering-Plough for the potential treatment of atherosclerosis and hypercholesterolemia. By January 2000, it was in phase III trials in the US [353762], [363364]. Schering-Plough is studying ezetimibe as a monotherapy for lowering lipid levels and, by February 2000, it was also planning combination studies with commonly used statin (HMG-CoA reductase inhibitor) therapies. The company believes that ezetimibe will have additive effects with the statins, inhibiting the absorption of cholesterol in the intestine while the statins work by inhibiting the production of cholesterol in the liver [363364]. In May 2000, Merck signed an agreement with Schering-Plough to develop and market in the US a once-daily, fixed-combination tablet with simvastatin (Zocor) [368021]. This combination has been shown to improve LDL reduction to 52% as compared to 35% with Zocor alone [375966].
Restenosis is a complicated disease. Neointima formation and unfavorable remodeling seem to contribute to the development of restenosis after angioplasty. Remodeling, a relatively new hypothesis, might be more crucial than neointima formation, although the two could well be inter-related. Stenting prevents unfavorable remodeling to some extent and lowers restenosis rates as compared to conventional balloon angioplasty. However, restenosis still occurs at too high a rate with stent angioplasty. A great many drugs have been tested in humans for the prevention of restenosis and failed, as most addressed the neointima formation problem only. Future drug design for restenosis should address both remodeling and neointima formation and some antioxidants, such as probucol, have shown promising results in this respect.
A series of 5-alkyltryptamines (6) and the corresponding conformationally constrained analogues (8) have been synthesized. The structure activity relationships (SAR) at the 5-position of the indole skeleton and the ethylamine side chain have been studied. Functional activities were assessed using isolated rabbit saphenous vein. Potent, selective ligands were found (6e, Ki 2.5 nM, 5-HT1B/5-HT1D 125-fold) that have potential for treating acute migraine.
A series of 5-(2- or 3-thienyl)tryptamine derivatives (9) has been synthesized and shown to be potent and selective 5-HT1D versus 5-HT1B receptor agonists and, therefore, potential treatments for migraine.