Monoaryl- and bisaryldihydroxytropolones as potent inhibitors of inositol monophosphatase.

The first successful preparation of mono- and disubstituted 3,7-dihydroxytropolone involves a four-step synthetic scheme. Thus, bromination of 3,7-dihydroxytropolone (8) followed by permethylation of the resultant products furnished gram quantities of intermediates 13-18. Single or double Suzuki coupling reactions between these permethylated monobromo- and dibromodihydroxytropolone derivatives and a variety of boronic acids delivered the expected products whose deprotection yielded the desired compounds 1a-u and 26a-n, usually in fair to good yields.

Synthesis of 5- and 6-fluoro derivatives of 5,8,14-eicosatrienoic and 5,8,11,14-eicosatetraenoic acids. Effects of fluorinated arachidonic acids on leukotriene C4 production by macrophages.

The total syntheses of the 5- and 6-fluoro derivatives of 5,8,14-eicosatrienoic (ETA) and arachidonic (AA) acids are described. The fluorinated double bond was introduced using (E)-1,4-dihydroxy-2-fluoro-2-butene obtained through diisobutylaluminium hydride reduction of dimethylfluoromaleate. Recently, 5-fluoro and 6-fluoro arachidonic acids (5-F-AA and 6-F-AA) were found to be effective inhibitors of 5-lipoxygenase in vitro (Nave, J.

Evaluation of 5- and 6-fluoro derivatives of arachidonic acid and 5,8,14-eicosatrienoic acid as substrates and inhibitors of 5-lipoxygenase.

The 5- and 6-fluoro derivatives of arachidonic acid (5F-ETE and 6F-ETE) were evaluated as substrates of rat basophilic leukaemia cell (RBL-1) 5-lipoxygenase. 5F-ETE was found to be a poor substrate and was converted into a single product, 5-oxoeicosa-6,8,11,14-tetraenoic acid (5-oxo-ETE). 6F-ETE was a good substrate and was mainly converted into 5-hydroperoxy-6-fluoroeicosa-6,8,11,14-tetraenoic acid (5-OOH-6F-ETE) with concomitant formation of a small amount of 5-oxo-6-fluoroeicosa-6,8,11,14-tetraenoic acid (5-oxo-6F-ETE).

New potent alpha-glucohydrolase inhibitor MDL 73945 with long duration of action in rats.

Inhibition of intestinal alpha-glucohydrolase activity is one approach for reducing the glycemic response from dietary carbohydrate and may prove useful for the treatment of diabetes mellitus. In this article, we describe the pharmacological properties of a time-dependent intestinal alpha-glucohydrolase inhibitor, MDL 73945. When preincubated 2 h with a rat intestinal mucosa preparation before substrate addition, MDL 73945 was a potent inhibitor of sucrase, maltase, glucoamylase, and isomaltase activities (MDL 73945 concentrations required to cause a 50% decrease in enzyme activity, 2 x 10(-7), 1 x 10(-6), 5 x 10(-6), and 8 x 10(-6) M, respectively); without preincubation, it was 10- to 500-fold less potent.

2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid. A potent irreversible inhibitor of diaminopimelic acid epimerase. Spontaneous formation from alpha-(halomethyl)diaminopimelic acids.

2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid (3) (aziridino-DAP) was identified as the product of spontaneous hydrolysis of alpha-(halomethyl)diaminopimelic acids (alpha-halomethyl-DAPs) 2a-c. Under physiological conditions, 3 is an extremely potent irreversible inhibitor of the bacterial enzyme diaminopimelic acid epimerase (DAP-epimerase; EC 5.1.