Biotech Values

[biomaven0]

Other folks have apparently looked at fumaric acid derivatives in attempt to get an "improved niacin":

Bioorg Med Chem Lett. 2011 May 1;21(9):2736-9. Epub 2010 Nov 25.
Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A).
van Veldhoven JP, Blad CC, Artsen CM, Klopman C, Wolfram DR, Abdelkadir MJ, Lane JR, Brussee J, Ijzerman AP.
Source
Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Abstract
Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. We synthesized a novel series of substituted propenoic acids, such as fumaric acid esters, fumaric acid amides and cinnamic acid derivatives, and determined their affinities for the HCA2 receptor. We observed a rather restricted binding pocket on the receptor with trans-cinnamic acid being the largest planar ligand in our series with appreciable affinity for the receptor. Molecular modeling and analysis of the structure-activity relationships in the series suggest a planar trans-propenoic acid pharmacophore with a maximum length of 8Å and out-of-plane orientation of the larger substituents.

And this recent article:

Diabetes Obes Metab. 2011 Mar 21. doi: 10.1111/j.1463-1326.2011.01400.x. [Epub ahead of print]
Future of GPR109A agonists in the treatment of dyslipidemia.
Wanders D, Judd RL.
Source
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States.
Abstract
Abnormal blood lipids are the major modifiable risk factor underlying the development of cardiovascular disease. Niacin has a profound ability to reduce LDL-C, VLDL-C and triglycerides, and is the most effective pharmacological agent to increase HDL-C. Recently, the receptor for niacin, GPR109A, was discovered. GPR109A in the adipocyte mediates a niacin-induced inhibition of lipolysis, which could play a crucial part in its role as a lipid-modifying drug. GPR109A in epidermal Langerhans cells mediates flushing, an unwanted side effect of niacin therapy. For the past decade, the functions of GPR109A have been studied and full or partial agonists have been developed in an attempt to achieve the beneficial effects of niacin while avoiding the unwanted flushing side effect. This review will present what is known to date about GPR109A biology and function and the future of GPR109A as a pharmacological target.