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SUBSTITUTED HETEROCYCLIC COMPOUNDS

The present invention relates to substituted heterocyclic compounds of Formula I or XI: or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine II4 receptor inhibitors useful in the treatment of histamine II4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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On the way to biodegradable poly(hydroxy butyrate) from propylene oxide and carbon monoxide via beta-butyrolactone: Multisite catalysis with newly designed chiral indole-imino chromium(III) complexes

Enantioenriched poly(hydroxy butyrate) (PHB) is a biodegradable polyester of significant commercial interest as an environmentally benign substitute of commodity polyolefines. We report on the design and development of new chiral indole-based ligand families and on their chromium(III) complexes as enantioselective catalysts for the conversion of propylene oxide and carbon monoxide to enantioenriched beta-butyrolactone, the key monomer for the production of PHB by ring-opening polymerization. The enantioselective carbonylation catalysts are based on new chiral tri- and tetradentate [N2O] and [N4] chromium(III) complexes containing chiral indolaldimine ligand scaffolds. The conceptual design of these ligands is inspired by Jacobsen’s salicylaldimine lead structure; the key difference is an exchange of the salicyl-O-donor against an indole-N-donor, allowing additional structural diversity and stereoelectronic tuning by the indole substitution pattern. Synthetically, chiral indolealdimines are easily accessible from 7-formylindoles by standard Schiff base condensation with chiral amine building blocks; the 7-formylindoles in turn are synthesized from the corresponding 7-bromoindoles by the Rapoport synthesis, and the starting 7-bromoindoles are accessible from 2-bromoaniline by the classical Fischer indole synthesis. Three generations of chiral [N2O] and [N4] chromium(III) catalysts have been developed and evaluated in the enantioselective carbonylation of racemic propylene oxide with carbon monoxide using tetracarbonylcobaltate as the nucleophilic reagent for the insertion of carbon monoxide into the activated propylene oxide/chiral Lewis acid complex. The best catalyst out of 10 candidates showed at a temperature of 80 C an activity of 37% conversion, 100% chemoselectivity, and 19% stereoselectivity.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Enantioselective access to bicyclo[4.2.0]octanes by a sequence of [2+2] photocycloaddition/reduction/fragmentation

Tricks of the trade: Because intramolecular Cu-catalyzed access to bicyclo[4.2.0]octanes is not feasible, an oxygen bridge was introduced to facilitate the [2+2] photocycloaddition. Starting from compounds similar to 1, products such as 2 could be obtained enantioselectiviely in three steps after ring-opening metathesis (see scheme). Copyright

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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HIV-1 protease inhibitors with a transition-state mimic comprising a tertiary alcohol: Improved antiviral activity in cells

By a small modification in the core structure of the previously reported series of HIV-1 protease inhibitors that encompasses a tertiary alcohol as part of the transition-state mimicking scaffold, up to 56 times more potent compounds were obtained exhibiting EC50 values down to 3 nM. Three of the inhibitors also displayed excellent activity against selected resistant isolates of HIV-1. The synthesis of 25 new and optically pure HIV-1 protease inhibitors is reported, along with methods for elongation of the inhibitor P1? side chain using microwave-accelerated, palladium-catalyzed cross-coupling reactions, the biological evaluation, and X-ray data obtained from one of the most potent analogues cocrystallized with both the wild type and the L63P, V82T, I84 V mutant of the HIV-1 protease.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality

Based on the unique property of sulfoximine and the homodimeric C2 structural symmetry of HIV-1 protease, a novel class of sulfoximine-based pseudosymmetric HIV-1 protease inhibitors was designed and synthesized. The sulfoximine moiety was demonstrated to be important for HIV-1 protease inhibitor potency. The most active stereoisomer (2S,2?S) displays a potency of 2.5 nM (IC50) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC50). A possible mode of action is proposed.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Highly enantioselective carbonyl reduction with borane catalyzed by chiral spiroborate esters derived from chiral 1,2-aminoalcohols

Novel spiroborate esters derived from nonracemic 1,2-amino alcohols were examined as chiral catalysts in the borane reduction of acetophenone and other aromatic ketones at room temperature. The optically active alcohols were obtained in excellent chemical yields and enantioselectivities up to 99% ee with 10% of catalyst.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Bimetallic titanium complex catalyzed enantioselective oxidation of thioethers using aqueous H2O2 as a terminal oxidant

A series of dimeric amino alcohol derived Schiff bases with various chiral amino alcohols and their corresponding bimetallic titanium complex were generated in situ. Thereafter with the in situ generated complexes, the asymmetric oxidation of prochiral aryl alkyl sulfides has been investigated using aqueous H2O2 as a terminal oxidant. During the study we found that the use of methanol or tert-butanol as an additive improved the catalytic activity in terms of both conversion and enantioselectivity. Moreover we observed a co-operative effect of the two reactive units of the bimetallic complex, which results in high reactivity as well as enantioselectivity compared to the corresponding monomeric complex. With this improved catalytic system several aryl alkyl sulfides and 1,3-dithianes were oxidised to the corresponding sulfoxides with good to high enantioselectivity (ee 78-99%) and conversion (70-99%). Unlike the monomer, oxidation of substrates like benzyl phenyl sulfide was achieved with high enantioselectivity as well as high yield.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Asymmetric synthesis of alpha-Amino acid derivatives via an electrophilic amination of chiral amide cuprates with Li t-Butyl-N-tosyloxycarbamate

The utility of lithium t-butyl-N-tosyloxycarbamate (LiBTOC) as a (+)NHBOC synthon in highly diastereoselective reactions with chiral cis-aminoindanol derived amide cuprates is described. The diastereoselectivities of these reactions ranged from 96% to greater than 99%. The subsequent transformation of these adducts to alpha-amino acids is also described.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR THEIR USE IN TREATING METABOLIC DISORDERS

The present invention provides compounds useful, for example, for modulating insulin levels in a subject, having the general formula I: wherein Q is an optionally substituted phenyl; L is a bond or O; P is a benzene or an optionally substituted thiazole ring; and R1 has the values provided herein. The present invention also provides compositions, uses, and methods for use of the compounds, for instance, for treatment of type II diabetes.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis