402933-40-8

Upstream product

• 39684-80-5 2-(tert-butoxycarbonylamino)ethyl bromide 
• 26690-80-2 2-(N-tert-butoxycarbonylamino)ethanol 
• 5446-02-6 4-methoxymethylsalicylate 

Downstream Products

• 1167415-56-6 8-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride 
• 1167415-84-0 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride 
• 1167416-18-3 8-[(phenylmethyl)oxy]-3,4-dihydro-1,4-benzoxazepin-5(2H)-one 
• 1167416-20-7 1,1-dimethylethyl 8-[(phenylmethyl)oxy]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 
• 1167416-25-2 1,1-dimethylethyl 8-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 
• 1167416-65-0 1,1-dimethylethyl 8-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 
• 1167416-19-4 8-[(phenylmethyl)oxy]-2,3,4,5-tetrahydro-1,4-benzoxazepine 
• 889107-83-9 2-[2-(tert-butoxycarbonylamino)ethoxy]-4-methoxybenzoic acid 

Relevant academic research and scientific papers

Optimization of sphingosine-1-phosphate-1 receptor agonists: Effects of acidic, basic, and zwitterionic chemotypes on pharmacokinetic and pharmacodynamic profiles

The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P1 receptors, while a variety of side effects have been ascribed to its S1P3 receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P1 receptor agonism. Here we describe a study of the tolerance of the S1P1 and S1P3 receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P1 receptor agonists with good selectivity vs S1P3 receptors, efficacy at 1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

ANTITHROMBOTIC DIAMIDES

This application relates to a compound of formula (I) (or a pharmaceutically acceptable salt of the compound) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa and/or thrombin, as well as a process for its preparation and intermediates therefor.