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[reaction: see text] A stereoselective total synthesis of (+)-benzastatin E (1) is described. The synthesis involves a diastereoselective Grignard addition to 2-acylindoline 2, which is derived from commercially available (S)-2-indolinecarboxylic acid (3). The unknown absolute configuration of (+)-1 is determined as (9S,10R).

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Reference:
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The first enantioselective heteroannulation of 1,3-dienes by 2-iodoanilines and 2-iodobenzylic alcohols is described. The application of a BINOL-derived phosphoramidite ligand bearing electron-withdrawing substituents is the key to obtaining high enantioselectivity. This protocol provides an efficient way to access optically active chiral indolines and isochromans from readily available starting materials.

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There is an urgent need for new, brain penetrant small molecules that target the central nervous system second stage of human African trypanosomiasis (HAT). We report that a series of novel indoline-2-carboxamides have been identified as inhibitors of Trypanosoma brucei from screening of a focused protease library against Trypanosoma brucei brucei in culture. We describe the optimization and characterization of this series. Potent antiproliferative activity was observed. The series demonstrated excellent pharmacokinetic properties, full cures in a stage 1 mouse model of HAT, and a partial cure in a stage 2 mouse model of HAT. Lack of tolerability prevented delivery of a fully curative regimen in the stage 2 mouse model and thus further progress of this series.

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Substituted spiroamine compounds corresponding to the formula (I) In which m, n, o, p, Q, r, s, t, R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7, R8, R9, R10 and R11 have defined meanings; a process for the preparation of such compounds, pharmaceutical compositions containing such compounds and the use of substituted spiroamines for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin 1 receptor.

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Metal catalyst and ligand design,
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ANTITHROMOBOTIC AGENTS

This invention relates to L-arginine aldehyde derivatives, having the Formula I STR1 where X and Y have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.

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Metal catalyst and ligand design,
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Oxazoline antiproliferative agents

Compounds having Formula I are useful for treating cancer. Also disclosed are pharmaceutical compositions comprising compounds of Formula I, and methods of treating cancer in a mammal.

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Synthesis of New Diketopiperazines, Thiolation to Thiodiketopiperazines, and Examination of Their ROS-Generating Properties

A variety of new symmetrical and unsymmetrical diketopiperazines have been prepared from free amino acids by using a previously developed microwave-assisted protocol. This included the successful incorporation of L-pyroglutamic acid as an unusual building block. The diketopiperazines were then thiolated electrophilically to the corresponding bis(methylthio)- and epidithiodiketopiperazines. Initial experiments showed a promising activity towards the generation of reactive oxygen species in HeLa cells. A variety of novel symmetrical and unsymmetrical thiodiketopiperazines have been prepared by methyl dichlorophosphite assisted dimerization of free amino acids and by thiolation of the resulting cyclic dipeptides with elemental sulfur and NaHMDS. Some of the sulfur compounds showed interesting activity in the generation of reactive oxygen species in HeLa cells.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Synthesis of New Diketopiperazines, Thiolation to Thiodiketopiperazines, and Examination of Their ROS-Generating Properties

A variety of new symmetrical and unsymmetrical diketopiperazines have been prepared from free amino acids by using a previously developed microwave-assisted protocol. This included the successful incorporation of L-pyroglutamic acid as an unusual building block. The diketopiperazines were then thiolated electrophilically to the corresponding bis(methylthio)- and epidithiodiketopiperazines. Initial experiments showed a promising activity towards the generation of reactive oxygen species in HeLa cells. A variety of novel symmetrical and unsymmetrical thiodiketopiperazines have been prepared by methyl dichlorophosphite assisted dimerization of free amino acids and by thiolation of the resulting cyclic dipeptides with elemental sulfur and NaHMDS. Some of the sulfur compounds showed interesting activity in the generation of reactive oxygen species in HeLa cells.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Process for the preparation of perindopril and salts thereof

The present invention relates to a process for the preparation of the ACE inhibitor (2S,3aS,7aS)-1-((2S)-2-(((1S)-1-(ethoxycarbonyl)butyl)amino)-1-oxopropyl)octahydro-1H-indol-2-carboxylic acid and of pharmaceutically acceptable salts thereof as well as to processes for preparing a N-((S)-1-carbethoxybutyl)-(S)-alanine intermediate and a (2S,3aS,7aS)-octahydroindole-2-carboxylic acid intermediate in a purified form.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Compounds for inhibiting beta-amyloid peptide release and/or its synthesis

Disclosed are compounds which inhibit beta-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer’s disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits beta-amyloid peptide release and/or its synthesis.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI