Since the original discovery of Weinreb [1], that N-methoxy-N-methyl amides 1, now popularly called as Weinreb amides (WA), cleanly reacted with Grignard reagents and organolithium to produce ketones, these amides have gained wide importance as very effective acylating agents for various organometallic reagents The esters and lactones have been invariably converted [5a -g] to Weinreb amides (Scheme 2) by using a combination of trimethyl aluminium and

The synthesis of (+)‐varitriol (1) analogues was achieved through the use of Julia olefination. The potential anticancer properties of 1 coupled with our interest in developing building blocks that enable olefin formation under the Julia protocol constitute the basis of our research project. Efforts are aimed at the synthesis of building blocks 2 and 3 and to explore their use towards the synthesis of (+)‐varitriol analogues. Herein, we would like to present the synthesis of building block 3 and its ability to react with variety of substituted aromatic‐, heterocyclic‐ and carbohydrate‐derived aldehydes to yield alkene 6 in moderate to good yields with E as the major isomer. The successful coupling of 2 with(furanoside moieties) aldehydes 5k, 5m and 5n in particular and the obtainment of compound 23 reflect the promise associated with the new strategy.

This work focuses on the study of aqueous phase aggregation of the recently FDA approved oral drug molecule FTY720 (fingolimod hydrochloride) and its effect on dimyristoylphosphatidylcholine (DMPC) liposomes using different fluorescent molecular probes and fluorescence parameters. The variation of the steady state fluorescence intensity of 8-anilino-1-naphthalene sulfonic acid (ANS) with FTY720 in water shows an efficient micellar aggregation with the critical micellar concentration (CMC) at ~75 μM. The aggregation number calculation from steady state fluorescence quenching of pyrene shows the formation of small micellar aggregates in aqueous solution having an aggregation number of 42 ± 3 with the free energy of micellization ~-23 kJ mol(-1). Fluorescence intensity and lifetime decay analysis of the molecular probe 1-naphthol indicate that the interaction of FTY720 with the DMPC lipid bilayer membrane prevents partitioning of small molecules such as 1-naphthol to the membrane in both solid gel (SG) and liquid crystalline (LC) phases. Temperature dependent fluorescence intensity studies of 1-naphthol and fluorescence anisotropy measurements of 1,6-diphenyl-1,3,5-hexatriene (DPH) have shown that above the CMC of FTY720, the SG to LC main phase transition temperature (T(M)) of the lipid bilayer membrane decreases from 23 °C to 21 °C in the aqueous medium.

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Lack of B 0 AT1 (SLC6A19) partially protects mice against the onset of non-alcoholic steatohepatitis (NASH). To achieve a similar outcome through pharmacological treatment, we improved previously identified inhibitors of B 0 AT1 by medicinal chemistry and identified second generation inhibitors by high through-put screening. Modified diarylmethine compounds inhibited B 0 AT1 with IC 50 values ranging from 8-90 mM. A second generation of inhibitors was derived from high-throughput screening and showed higher affinity (IC 50 of 1-15 mM) and strong selectivity against amino acid transporters with similar substrate specificity, such as ASCT2 (SLC1A5) and LAT1 (SLC7A5). All compounds were unrelated to B 0 AT1 substrates, but were likely to bind in the vicinity of the substrate binding site.