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Safety attrition of drugs during preclinical development as well as in late-stage clinical trials continues to be a challenge for the pharmaceutical industry for patient welfare and financial reasons. Hepatic, cardiac, and nephrotoxicity remain the main reasons for compound termination. In recent years, efforts have been made to identify such liabilities(More)
We consider linear instability of solitary waves of several classes of dispersive long wave models. They include generalizations of KDV, BBM, regularized Boussinesq equations, with general dispersive operators and nonlinear terms. We obtain criteria for the existence of exponentially growing solutions to the linearized problem. The novelty is that we dealt(More)
Lectin-like oxidized LDL (ox-LDL) receptor-1 (LOX-1) is a type-II transmembrane protein that belongs to the C-type lectin family of molecules. LOX-1 acts as a cell surface endocytosis receptor and mediates the recognition and internalization of ox-LDL by vascular endothelial cells. Internalization of ox-LDL by LOX-1 results in a number of pro-atherogenic(More)
This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and(More)
Abstract. To determine the stability and instability of a given steady galaxy configuration is one of the fundamental problems in the Vlasov theory for galaxy dynamics. In this article, we study the stability of isotropic spherical symmetric galaxy models f0(E), for which the distribution function f0 depends on the particle energy E only. In the first part(More)
The design of drugs with selective tissue distribution can be an effective strategy for enhancing efficacy and safety, but understanding the translation of preclinical tissue distribution data to the clinic remains an important challenge. As part of a discovery program to identify next generation liver selective HMG-CoA reductase inhibitors we report the(More)
We consider the stability of periodic gravity free-surface water waves traveling downstream at a constant speed over a shear flow of finite depth. In case the free surface is flat, a sharp criterion of linear instability is established for a general class of shear flows with inflection points and the maximal unstable wave number is found. Comparison to the(More)
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Münchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than(More)