Christopher A. Teleha

MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.

In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 microM for MEK 1 and 0.06 microM for MEK 2. U0126 can undergo isomerization and cyclization reactions to form a variety of products, both chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1 activity than parent, U0126.

Resolution of α-aminoboronic esters by diastereoselective crystallization with pinanediols. Confirmation by X-ray analysis

Abstract A resolution method for α-aminoboronic esters 4a,b using chiral pinanediol is described.

Acetylcholine release enhancers related to linopirdine: A structure—activity relationship study. II*

Summary Several series of α,α-disubstituted polycyclic compounds were found to enhance the stimulus-induced release of neurotransmitters, especially acetylcholine, in brain slices. This work resulted in the identification of linopirdine [3,3-bis (4-pyridinylmethyl)-1, 3-dihydro-1-phenyl-2 H -indol-2-one] 1a which was tested clinically for the treatment of Alzheimers disease. The structure-activity relationship (SAR) results suggest that the potency of the series was dependent on the nature of the pendent groups (R), the distance geometry produced by the pendant groups, and the hydrogen-bonding property of the core group.

A CONVENIENT SYNTHESIS OF N-Boc-4-FORMYLPIPERINE

The title compound, N-Boc-4-formylpiperidine (3), has been reported several times in recent years as a useful synthetic intermediate, particularly in the pharmaceutical industry. In the various methods that have been used for its preparation, at least one significant shortcoming exists which makes the reported syntheses unattractive for larger scale preparations. The drawbacks include the need for extremely expensive reagents,-* toxic/environmentally unfriendly reagents, extremely low temperatures, chromatographic purifications,s and/or malodorous by-products?-* In addition, some of these reported syntheses proceeded in only moderate overall yields. We report here a convenient, high yielding, cost-effective procedure which does not have the drawbacks of the previously reported procedures.