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An asymmetric approach to the cyclopentanol motif of the biologically active, marine natural product stolonidiol has been developed. The approach involves the asymmetric synthesis of chiral gamma,delta-unsaturated ketones and their spirocyclisation using SmI2. Georg Thieme Verlag Stuttgart.

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Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H2021NO – PubChem

 

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Provided herein are compounds, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or co-crystals and prodrugs thereof which have glucagon receptor antagonist or inverse agonist activity. Further, provided herein are pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistance and hyperglycemia. Moreover, provided herein are methods of making or manufacturing compounds disclosed herein, including enantiomerically pure forms thereof, and pharmaceutically acceptable salts or Co- crystals and prodrugs thereof. Formula I

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1594NO – PubChem

 

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GPR120 agonists have therapeutic potential for the treatment of diabetes, but few selective agonists have been reported. We identified an indazole-6-phenylcyclopropylcarboxylic acid series of GPR120 agonists and conducted SAR studies to optimize GPR120 potency. Furthermore, we identified a (S,S)-cyclopropylcarboxylic acid structural motif which gave selectivity against GPR40. Good oral exposure was obtained with some compounds displaying unexpected high CNS penetration. Increased MDCK efflux was utilized to identify compounds such as 33 with lower CNS penetration, and activity in oral glucose tolerance studies was demonstrated. Differential activity was observed in GPR120 null and wild-type mice indicating that this effect operates through a mechanism involving GPR120 agonism.

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Reference:
Oxazolidine – Wikipedia,
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The chiral glycine synthon, 3c, as its derived stannous enolate, has been demonstrated to undergo a highly syn diastereoselective aldol addition reaction with representative aldehydes to give the adducts 5 (R = C6H5, Me, Me2CH) in yields ranging from 71 to 92percent.The utility of these intermediates has been demonstrated via the subsequent three-step transformation of these adducts to the enantiomerically pure N-methyl beta-hydroxy amino acids 1.This reaction methodology has been applied to the asymmetric synthesis of (4R)-4-((E)-2-butenyl)-4,N-dimethyl-L-threonine (1a), an important constituent in the immunosuppressant peptide cyclosporine.Several additional structural analogues of 1a were also prepared in conjunction with this study.

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Oxazolidine – Wikipedia,
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Many lipolytic enzymes are enantioselective thus being able to distinguish between two enantiomers of a given racemic substrate. This property together with ample availability and comparatively easy handling makes lipolytic enzymes the most widely used class of biocatalysts in the chemical and pharmaceutical industries. However, lipase activity as well as selectivity is often negligible towards typical industrial substrates which usually do not resemble natural ones. Therefore, suitable enzymes must first be identified, usually by activity-based screening methods which, however, differ in reliability, throughput and surrogate function. Here, we describe important parameters determining the reliability and reproducibility of such screening systems for five different assays in detail. Moreover, comprehensive protocols for the synthesis of enantiopure lipase substrates and their use for screening of enantioselective lipases are provided.

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Oxazolidine – Wikipedia,
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The synthesis of a series of N-alkylated 4-(4?aminobenzyl)-2-oxazolidinones is described using a synthetically useful scheme which avoids the use of phosgene – since the derivatization is undertaken with the oxazolidin-2-one ring intact. The compounds were tested for human placental aromatase (AR) inhibition in vitro, using [1beta, 2beta-3H]androstenedione as substrate for the AR enzyme. The compounds were found, in general, to be more potent than the standard compound, amino-glutethimide (AG), and as such proved to be good lead compounds in the search for more specific AR inhibitors.

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Oxazolidine – Wikipedia,
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Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta2-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

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Oxazolidine – Wikipedia,
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The thiazolidinedione moiety of ciglitazone and its analogues can be replaced by an alpha-alkoxy or alpha-thioether carboxylic acid group. The influence of the nature of the R group, the length of the connector to the aromatic backbone of the molecule, and the stereochemistry have been studied. The most potent compounds have glucose-lowering activity at doses as low as 0.01 mg/kg.

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Five suitably protected enantiomerically pure beta2-amino acids, homologues of proteinogenic alpha-amino acids, were synthesized from the common chiral precursor, tert-butyl succinyloxazolidinone. Georg Thieme Verlag Stuttgart.

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A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S2? pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P2? substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.

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Reference:
Oxazolidine – Wikipedia,
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