189328-96-9

Upstream product

• 42969-65-3 (R)-(+)-3-butyn-2-ol 
• 141580-65-6 N,O-Bis(phenoxycarbonyl)hydroxylamine 

Relevant academic research and scientific papers

DUAL INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE AND 5-LIPOXYGENASE

The invention pertains to a novel structure (I) that provides an activity as a dual inhibitor of the enzymes soluble epoxide hydrolase (sEH) and 5-lipoxygenase (5-LOX). The invention pertains to multiple derivatives of the new class of dual inhibitors, their application in medicine, pharmaceutical compositions comprising them as well as to methods for synthesizing the new compounds.

Design, Synthesis, and Structure-Activity Relationship Studies of Dual Inhibitors of Soluble Epoxide Hydrolase and 5-Lipoxygenase

Inhibition of multiple enzymes of the arachidonic acid cascade leads to synergistic anti-inflammatory effects. Merging of 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase (sEH) pharmacophores led to the discovery of a dual 5-LOX/sEH inhibitor, which was subsequently optimized in terms of potency toward both targets and metabolic stability. The optimized lead structure displayed cellular activity in human polymorphonuclear leukocytes, oral bioavailability, and target engagement in vivo and demonstrated profound anti-inflammatory and anti-fibrotic efficiency in a kidney injury model caused by unilateral ureteral obstruction in mice. These results pave the way for investigating the therapeutic potential of dual 5-LOX/sEH inhibitors in other inflammation- and fibrosis-related disease models.

Substituted arylalkynyl-and heteroarylalkynl-N-hydroxyurea inhibitors of leukotriene biosynthesis

The invention relates to compounds having activity to inhibit lipoxygenase enzyme activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treating. More particularly, this invention concerns certain substituted arylalkynyl- and ((heteroaryl)alkynyl)-N-hydroxy-ureas which inhibit leukotriene biosynthesis, to pharmaceutical compositions of these compounds and to a method of inhibiting leukotriene biosynthesis.

Asymmetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea, a key intermediate for 5-lipoxygenase inhibitors

An efficient asymmetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea from crotyl alcohol is described. The process involves asymmetric Sharpless epoxidation to establish the stereochemistry, formation of (S)-3-butynol and hydroxyl substitution with inversion by the masked N-hydroxyurea reagent N,O-bis(phenoxycarbonyl)hydroxylamine in a Mitsunobu reaction.