Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist

Add time:09/24/2019    Source:sciencedirect.com

For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N′-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N′-phenylureido)phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α4 antibody (R1–2).

We also recommend Trading Suppliers and Manufacturers of 1-METHYL-1-CYCLOHEXANECARBOXYLIC ACID (cas 1123-25-7). Pls Click Website Link as below: cas 1123-25-7 suppliers

Prev:Microbial reduction of alpha-substituted-alpha-acetyl-gamma-butyrolactones
Next:Hymenoic acid, a novel specific inhibitor of human DNA polymerase λ from a fungus of Hymenochaetaceae sp.)