45223-18-5Relevant articles and documents
Synthesis of new ligands for targeting the S1P1 receptor
Schilson, Stefanie S.,Keul, Petra,Shaikh, Rizwan S.,Sch?fers, Michael,Levkau, Bodo,Haufe, Günter
, p. 1011 - 1026 (2015/03/04)
Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [18F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases.
Conformationally-locked N -glycosides: Exploiting long-range non-glycone interactions in the design of pharmacological chaperones for Gaucher disease
Castilla, Javier,Rísquez, Rocío,Higaki, Katsumi,Nanba, Eiji,Ohno, Kousaku,Suzuki, Yoshiyuki,Díaz, Yolanda,Ortiz Mellet, Carmen,García Fernández, José M.,Castillón, Sergio
supporting information, p. 258 - 266 (2015/01/08)
Pyranoid-type glycomimetics having a cis-1,2-fused glucopyranose-2-alkylsulfanyl-1,3-oxazoline (Glc-PSO) structure exhibit an unprecedented specificity as inhibitors of mammalian β-glucosidase. Notably, their inhibitory potency against human β-glucocerebrosidase (GCase) was found to be strongly dependent on the nature of aglycone-type moieties attached at the sulfur atom. In the particular case of υ-substituted hexadecyl chains, an amazing influence of the terminal group was observed. A comparative study on a series of Glc-PSO derivatives suggests that hydrogen bond acceptor functionalities, e.g. fluoro or methyloxycarbonyl, significantly stabilize the Glc-PSO:GCase complex. The S-(16-fluorohexadecyl)-PSO glycomimetic turned out to be a more potent GCase competitive inhibitor than ambroxol, a non glycomimetic drug currently in pilot trials as a pharmacological chaperone for Gaucher disease. Moreover, the inhibition constant increased by one order of magnitude when shifting from neutral (pH 7) to acidic (pH 5) media, a favorable characteristic for a chaperone candidate. Indeed, the fluoro-PSO derivative also proved superior to ambroxol in mutant GCase activity enhancement assays in N370S/N370S Gaucher fibroblasts. The results presented here represent a proof of concept of the potential of exploiting long-range non-glycone interactions for the optimization of glycosidase inhibitors with chaperone activity.
First syntheses of model long-chain trichloro[ω-(trimethylsilyl)alkynyl]silanes suitable for self-assembled monolayers on silicon surfaces
Banaszak, Estelle,Xu, Li-Wen,Bardeau, Jean-Fran?ois,Castanet, Anne-Sophie,Mortier, Jacques
body text, p. 3961 - 3966 (2009/09/30)
The preparation of the title compounds involves the introduction of the required Me3SiC{triple bond, long}C and trichlorosilyl groups at the termini of the alkyl chain via derivatization of easily accessible and inexpensive materials/reagents. Trichloro[ω-(trimethylsilyl)alkynyl]silanes are useful for the linkage to a hydroxylated silicon surface for multilayer formation and for further chemical modification of the tail group of the monolayer.
