956036-91-2

Upstream product

• 956037-35-7 N-[5-[2-(4'-bromo-2'-fluorobiphenyl-4-yl)ethyl]-2,2-dimethyl-1,3-dioxane-5-yl]acetamide 
• 2557-77-9 3-fluorothiophenol 

Relevant academic research and scientific papers

Removal of sphingosine 1-phosphate receptor-3 (S1P3) agonism is essential, but inadequate to obtain immunomodulating 2-aminopropane-1,3-diol S1P1 agonists with reduced effect on heart rate

A series of 2-substituted 2-aminopropane-1,3-diols having a biphenyl moiety and their phosphate esters were synthesized to obtain sphingosine 1-phosphate receptor-1 (S1P1) receptor agonists with potent immunomodulatory activity accompanied by little or no effect on heart rate. Many of the synthesized compounds sufficiently decreased the number of peripheral blood lymphocytes. Some of the phosphates had potent agonism at S1P1 but no agonism at S1P3, which had been reported to be a receptor responsible for heart rate reduction. Although high S1P1/S1P 3 selectivity was considered to be favorable to reduce the effect on heart rate, almost all the phosphates showed a remarkable heart rate lowering effect in vivo. The results suggest that other factors in addition to S1P 3 agonism should be responsible for the heart rate reduction caused by S1P1 agonists. Only 2-amino-2-[2-[2′-fluoro-4′-(4- methylphenylthio)biphenyl-4-yl]ethyl]propane-1,3-diol (6d) was identified as a desired S1P1 receptor agonist having both the immunomodulatory activity and an attenuated effect on heart rate by a unique screening flow using in vivo evaluating systems primarily.

2-AMINOBUTANOL COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES

The present invention provides a novel compound having few side effects such as bradycardia and the like and having superior peripheral blood lymphocyte-decreasing effect. The present invention provides a 2-aminobutanol compound represented by the following formula (I) wherein R1 is a hydrogen atom or P(=O)(OH)2, R2 is an alkyl having 1 to 4 carbon atoms optionally substituted by hydroxyl group(s) or optionally substituted by halogen atom(s), R3 is a hydrogen atom; a halogen atom; cyano; an alkyl having 1 to 4 carbon atoms optionally substituted by halogen atom(s); or an acyl having 2 to 5 carbon atoms optionally substituted by halogen atom(s), X is an oxygen atom, a sulfur atom, carbonyl or NR4 wherein R4 is a hydrogen atom or an alkyl having 1 to 4 carbon atoms, Ar1 is an optionally substituted arylene or an optionally substituted heteroarylene, and Ar2 is an optionally substituted aryl or an optionally substituted heteroaryl, provided that when X is an oxygen atom, Ar1 is phenylene and Ar2 is phenyl, then the phenyl for Ar2 should be substituted, or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, or a solvate thereof, as well as a production method of the above-mentioned 2-aminobutanol compound.