A novel and potent VLA-4 antagonist based on trans-4-substituted cyclohexanecarboxylic acid

Add time:08/16/2019    Source:sciencedirect.com

During the course of our study, it was revealed that the poor pharmacokinetic properties of a series of benzoic acid derivatives such as 1 should be attributed to the diphenylurea moiety. Thus, we replaced the diphenylurea moiety in 1 with a 2-(2-methylphenylamino)benzoxazole moiety which mimics the diphenylurea structure. However, this modification resulted in a significant decrease (3, IC50 = 19 nM) in VLA-4 inhibitory activity compared to 1 (IC50 = 1.6 nM). To address this discrepancy, we worked on optimization of the carboxylic acid moiety in compound 3. As a result, our efforts have led to the discovery of trans-4-substituted cyclohexanecarboxylic acid derivative 11b (IC50 = 2.8 nM) as a novel and potent VLA-4 antagonist. In addition, compound 11b exhibited favorable pharmacokinetic properties (CL = 3.3 ml/min/kg, F = 51%) in rats.

We also recommend Trading Suppliers and Manufacturers of 3-Amino-2-(4-methylphenylamino)benzoic acid (cas 116702-65-9). Pls Click Website Link as below: cas 116702-65-9 suppliers

Prev:Design, synthesis and in vitro evaluation against human cancer cells of 5-methyl-5-styryl-2,5-dihydrofuran-2-ones, a new series of goniothalamin analogues
Next:Synthesis of chiral β-amino acid derivatives by asymmetric hydrosilylation with an imidazole derived organocatalyst)