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Compounds having the formula are useful for treating conditions which arise from or are exacerbated by angiogenesis. Also disclosed are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting angiogenesis, and methods of treating cancer.

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The asymmetric synthesis of LY309887, a cytotoxic dideazatetrahydrofolate analog related to lometrexol, has been accomplished via an application of diastereoselective amidomethylation of a chiral titanium (IV) acyloxazolidinone enolate.

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Compounds that modulate gamma secretase (e.g., alter the cleavage pattern of gamma secretase) are described herein. Also disclosed are pharmaceutical compositions, methods of modulating the activity of gamma secretase, and methods of treating Alzheimer¿s Disease using the compounds described herein.

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Four novel analogues of antimycin A3, 1a-d, were synthesized in good overall yields.

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Diels-Alder reactions of 1,4-naphthoquinones bearing a chiral auxiliary at C-2, with cyclopentadiene under Lewis acid conditions afforded the corresponding Diels-Alder adducts. High levels of diastereomeric excess were obtained using (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide and trans- 2-phenylcyclohexanol as auxiliaries. Moderate asymmetric induction was achieved using Oppolzer’s camphorsultam and (R)-(+)-4-benzyl-2-oxazolidinone as auxiliaries. X-Ray crystallographic analysis of the pantolactone adduct enabled determination of the stereochemistry of all adducts obtained.

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The synthesis of the chiral core structure of the lissoclimide class of anti-tumour agents containing three rings, including a chiral succinimide subunit and an exocyclic double bond, has been investigated. The compound 7 was obtained, without the use of any protecting groups for the alcohol at C-12, via an asymmetric boron-mediated aldol addition as the key step to install the chiral centres of the rare succinimido methanol moiety. This was followed by a sequence of lactonisation, microwave-assisted amidation and imidation reactions.

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Tripeptide analogs of the form Cbz-GlyPsi[(Z/-CF=CH]LeuXaa (1, Xaa = Gly, Ala, Leu, Phe, and NH2) were synthesized to assess the ability of the fluoroalkene moiety to mimic a peptide linkage. These compounds are modest inhibitors of the zinc endopeptidase thermolysin (0.19 mM < K(i) < 1.8 mM); the K(i) values correlate strongly with the K(m) values, but not K(m)/k(cat), for hydrolysis of the corresponding peptides. The correlation indicates that these inhibitors bind as ground state analogs and represent the first direct assessment of the fluoroalkene unit as a peptide surrogate. The reactant in an enzyme-catalyzed reaction is called a substrate. Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction.I hope my blog about 102029-44-7 is helpful to your research. Computed Properties of C10H11NO2.

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A highly stereoselective total synthesis of amphidinolide T1 is achieved using Sharpless asymmetric epoxidation, base-induced epoxide opening, radical cyclization, diastereoselective reduction followed by allylation, Evans methylation, base-induced reductive elimination, umpolung reaction, chemoselective oxidation, and regioselective macrolactonization.

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A stereoselective total synthesis of 13-membered macrocycle PF1163A, an antifungal agent, has been accomplished for the first time starting from d-xylose. This approach involves a diastereoselective allylation of lactal ether,3a reductive ring opening of tetrahydrofuran ring,3b asymmetric methylation reaction, Yamaguchi esterification, and ring closing metathesis as key steps.

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Previous reports from our laboratories described potent tripeptide thrombin inhibitors which incorporate heterocycle-substituted chlorophenyl groups in the P1 position. Using these as lead compounds for further optimization, we identified sites of metabolism and designed analogs with 4-fluoroproline in P2 and cyclopropane-containing side chains in P3 as an approach to reducing metabolism and improving their oral pharmacokinetic performance. The large (300-fold) difference in potency between analogs containing (4R)- and (4S)-4-fluoroproline was rationalized by analyzing inhibitor-enzyme interactions in crystal structures of related compounds and by molecular modeling which indicated that the more potent (4R)-4-fluoroproline isomer stabilizes a proline ring conformation that is preferred for binding to the enzyme. An optimal compound from this work, 41, exhibits high potency in a coagulation assay in human plasma (2×APTT = 190 nM), excellent selectivity versus the digestive enzyme trypsin (Ki = 3300 nM), and excellent oral bioavailability in dogs with moderate clearance (F = 100%, CL = 12 mL/min/kg).

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