David L. Hageman

Convenient Preparations of t-Butyl Esters and Ethers from t-Butanol

Abstract A one-pot preparation of t-butyl esters and ethers is described that proceeds from the carboxylic acid or alcohol and t-butanol using only anhydrous magnesium sulfate and catalytic sulfuric acid as additional reagents. The method affords t-butyl esters and ethers in good yields and is applicable to a variety of substrates.

3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site.

3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.

Allosteric inhibition of fructose-1,6-bisphosphatase by anilinoquinazolines

Anilinoquinazolines currently of interest as inhibitors of tyrosine kinases have been found to be allosteric inhibitors of the enzyme fructose 1,6-bisphosphatase. These represent a new approach to inhibition of F16BPase and serve as leads for further drug design. Enzyme inhibition is achieved by binding at an unidentified allosteric site.

A convenient modification of the Gassman oxindole synthesis

Abstract A modification of the Gassman oxindole synthesis is described that proceeds from anilines and ethyl (methylsulfinyl)acetate, using oxalyl chloride to activate the sulfoxide to facilitate the formation of the key N - S bonded intermediate. This procedure is particularly convenient for reactions carried out on smaller scales and for anilines that are susceptible to electrophilic halogenation.

CP-70,030 and CP-75,998: The first non-peptide antagonists of bombesin and gastrin releasing peptide

Abstract CP-70,030 and CP-75,998 were identified in a screening program as compounds able to displace [125I]-gastrin releasing peptide (GRP) from its rat brain receptor. We describe here the syntheses of these compounds and their characterization as bonafide GRP antagonists.

A synthesis of functionalized indoline 2,2-biscarboxylates

Abstract A synthetic approach to a structurally novel series of indoline 2,2-biscarboxylates is described that employs a tandem bis-alkylation strategy to cyclize the indoline heteroring from the bromide 7 and diethyl bromomalonate. The indolines thus prepared may be N-deprotected and further functionalized on the indoline nitrogen.