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• 762-62-9 4,4-dimethylpent-1-ene 

Relevant academic research and scientific papers

Formation of both primary and secondary N-alkylhemins during hemin-catalyzed epoxidation of terminal alkenes

The N-alkylhemin formation during iron(III) porphyrin-catalyzed epoxidation of alkenes is studied in a homogeneous system using pentafluoroiodosobenzene (PFIB) as the oxidant. The system is a model for the enzyme cytochrome P-450. A second N-alkyl species

Substrate Enantioselection in the Microsomal Epoxide Hydrolase Catalyzed Hydrolysis of Monosubstituted Oxiranes. Effects of Branching of Alkyl Chains

The hydrolysis of racemic 1,2-epoxyhexane (1a), 1,2-epoxydecane (1b), 4,4-dimethyl-1,2-epoxypentane (1c), and 3,3-dimethyl-1,2-epoxybutane (1d) catalyzed by rabbit liver microsomal epoxide hydrolase (MEH) has been investigated in order to further clarify the enantioselecting ability of this enzyme.Both enantiomers of all four epoxides were good substrates.The alkyl chain showed, however, a remarkable effect on the enantiomeric excess of the diols 2 produced during the course of the hydrolysis under enzyme saturation conditions.Linear-chain epoxides gave diols with very low enantiomeric excesses even at very low conversions, whereas branched-chain epoxides gave enantiomerically enriched diols.Furthermore, the ee obtained with the latter epoxides increased with increasing ratio of substrate to microsomal protein.R configurations were demonstrated for the excess enantiomers of diols 2c and 2d by CD and NMR measurements of their dibenzoate esters.In the case of 1c nucleophilic attack by water was proved using 18OH2 followed by MS analysis of the produced diol to occur 95percent at the unsubstituted oxirane carbon.A markedly biphasic profile was found for the time course of the hydrolysis of (+/-)-1d.A mechanistic explanation for the observed substrate enantioselection is proposed.

Regioselectivity and diasteroselectivity in Pt(II)-mediated "green" catalytic epoxidation of terminal alkenes with hydrogen peroxide: Mechanistic insight into a peculiar substrate selectivity

Recently developed electron-poor Pt(II) catalyst 1 with the "green" oxidant 35% hydrogen peroxide displays high activity and complete substrate selectivity in the epoxidation of terminal alkenes because of stringent steric and electronic requirements. In the presence of isolated dienes bearing terminal and internal double bonds, epoxidation is completely regioselective toward the production of terminal epoxides. Insight into the mechanism is gained by means of a reaction progress kinetic analysis approach that underlines the peculiar role of 1 in activating both the alkene and H 2O2 in the rate-determining step providing a rare example of nucleophilic oxidation of alkenes by H2O2.

INHIBITORS OF CATHEPSIN S

The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: Synthesis, x-ray crystallographic analysis, and biological activities

High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC50 values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase α (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.