The preparation of ester heterocycles mostly uses heteroatoms as nucleophilic sites, which are achieved by intramolecular substitution or addition reactions. Compound: 1-Bromoundecane( cas:693-67-4 ) is researched.Recommanded Product: 1-Bromoundecane.Congdon, Molly; Fritzemeier, Russell G.; Kharel, Yugesh; Brown, Anne M.; Serbulea, Vlad; Bevan, David R.; Lynch, Kevin R.; Santos, Webster L. published the article 《Probing the substitution pattern of indole-based scaffold reveals potent and selective sphingosine kinase 2 inhibitors》 about this compound( cas:693-67-4 ) in European Journal of Medicinal Chemistry. Keywords: alkylindolyl oxadiazolylpyrrolidine preparation sphingosine kinase inhibition SAR mol docking; Molecular docking; SAR; SphK2; Sphingosine; Sphingosine 1-phosphate; Sphingosine kinase. Let’s learn more about this compound (cas:693-67-4).
Elevated levels of sphingosine 1-phosphate (S1P) and increased expression of sphingosine kinase isoforms (SphK1 and SphK2) have been implicated in a variety of disease states including cancer, inflammation, and autoimmunity. Selective inhibition of either SphK1 or SphK2 has been demonstrated to be effective in modulating S1P levels in animal models. Previously, authors reported a SphK2 naphthalene-based selective inhibitor, (R)-2-(3-(7-(pentyloxy)naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide hydrochloride, which displays approx. 7-fold selectivity for hSphK2 over hSphK1 and has a SphK2 Ki value of 1.0μM. To improve SphK2 potency and selectivity, author’s designed, synthesized, and evaluated a series of indole-based compounds derived from (R)-2-(3-(7-(pentyloxy)naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboximidamide hydrochloride. After investigating substitution patterns around the indole ring, author’s discovered that 1,5-disubstitution promoted optimal binding in the SphK2 substrate binding site and subsequent inhibition of enzymic activity. Author’s studies led to the identification of I (SphK2 Ki = 90 nM, >110 fold selective for SphK2 over SphK1). Mol. modeling studies revealed key nonpolar interactions with Val308, Phe548, His556, and Cys533 and hydrogen bonds with both Asp211 and Asp308 as responsible for the high SphK2 inhibition and selectivity.
When you point to this article, it is believed that you are also very interested in this compound(693-67-4)Recommanded Product: 1-Bromoundecane and due to space limitations, I can only present the most important information.
Reference:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem