Design and synthesis of thrombin inhibitors: analogues of MD-805 with reduced stereogenicity and improved potency.

Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibitors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.

2,4,6-tris{2'[4'-(p-sulfophenyl)pyridyl]}-s-triazine: a new analytical reagent for the spectrophotometric determination of iron.

The sulfonated analog (TPPTZ-S) of 2,4,6-tris[2'-(4'-phenylpyridyl)]-s-triazine has been synthesized and its analytical utility investigated. The characteristics of the iron(II) complex of this ligand, including optimum conditions of formation, adherence to Beer's law and relative stability are described. Procedures for the quantitative determination of trace amounts of iron with TPPTZ-S are given.

A high-precision titration of 4-aminopyridine A value for the faraday.

A specimen of 4-aminopyridine purified by repeated sublimation in an atmosphere of nitrogen has been titrated coulometrically in two ways: (1) directly, using the hydrazine-platinum anode, and (2) with perchloric acid, the titration being completed coulometrically and the perchloric acid being standardized coulometrically. The values for the faraday calculated from these titrations are 96,486.40 (1.

An electrode for the coulometric generation of hydrogen ion.

The anodic generation of hydrogen ion on bright platinum in 1.0M sodium perchlorate is not quantitative owing to the formation of a chemical species With oxidizińg properties, presumably a peroxydiperchlorate, but 100% current efficiency can be obtained in the anodic generation of hydrogen in 0.25M sodium hydrazinium sulphate, Na(N(2)H(5))SO(4).