843675-75-2

Upstream product

• 79887-09-5 (4-butylphenyl)acetylene 
• 1122-91-4 4-bromo-benzaldehyde 
• 15164-44-0 p-(iodophenyl)carboxaldehyde 

Downstream Products

• 866931-47-7 N-{4-[(4-butylphenyl)ethynyl]benzyl}-1-hexanamine 
• 843676-57-3 methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate 
• 866931-40-0 1-{4-[(4-butylphenyl)ethynyl]phenyl}-1-pentanol 
• 866931-15-9 {4-[(4-butylphenyl)ethynyl]benzyl}[2-(4-chlorophenyl)ethyl]amine 
• 843675-76-3 6-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one 

Relevant academic research and scientific papers

Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors

The sphingosine 1-phosphate (S1P) signaling pathway is an attractive target for pharmacological manipulation due to its involvement in cancer progression and immune cell chemotaxis. The synthesis of S1P is catalyzed by the action of sphingosine kinase 1 or 2 (SphK1 or SphK2) on sphingosine and ATP. While potent and selective inhibitors of SphK1 or SphK2 have been reported, development of potent dual SphK1/SphK2 inhibitors are still needed. Towards this end, we report the structure–activity relationship profiling of 2-(hydroxymethyl)pyrrolidine-based inhibitors with 22d being the most potent dual SphK1/SphK2 inhibitor (SphK1 Ki = 0.679 μM, SphK2 Ki = 0.951 μM) reported in this series. 22d inhibited the growth of engineered Saccharomyces cerevisiae and decreased S1P levels in histiocytic lymphoma myeloid cell line (U937 cells), demonstrating inhibition of SphK1 and 2 in vitro. Molecular modeling studies of 22d docked inside the Sph binding pocket of both SphK1 and SphK2 indicate essential hydrogen bond between the 2-(hydroxymethyl)pyrrolidine head to interact with aspartic acid and serine residues near the ATP binding pocket, which provide the basis for dual inhibition. In addition, the dodecyl tail adopts a “J-shape” conformation found in crystal structure of sphingosine bound to SphK1. Collectively, these studies provide insight into the intermolecular interactions in the SphK1 and 2 active sites to achieve maximal dual inhibitory activity.

ALKYNYL ARYL CARBOXAMIDES

The present invention is related to alkynyl aryl carboxamides of Formula (I’) and use thereof for the treatment and/or prevention of an inflammatory disorder, obesity and/or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance. insulin resistance, hyperlipidemia, hypertriglyceridemia- hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of alkynyl aryl carboxamides of Formula (I’) to modulate, notably to inhibit the activity of PTPs. (I’) A is a C2-C15 alkynyl, C2-C6-alkynyl aryl, C2-C6-alkynyl heteroaryl. Cy is an aryl, heteroaryl, cycloalkyl or heterocycle group; n is either 0 or 1. Cy' is an aryl., which may optionally be fused by a 3-8 membered cycloalkyl. R1and R2 are independently from each other is selected from the group consisting of hydrogen or (CI-C6)alkyl. R4and R5 are each independently from each other selected from the group consisting of H, hydroxy. C1 -C6 alkyl, carboxy, C1-C6 alkoxy, C1 -C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.