Amino acids and peptides. XIII. Synthetic studies on N-terminal tripeptide amide analogs of fibrin alpha-chain

N-Terminal tripeptide analogs of fibrin alpha-chain were synthesized and their inhibitory effect on fibrinogen/thrombin clotting was examined. A new water-soluble active ester, 3-pyridinium ester, was used for the synthesis. Among the synthetic peptides, H-Gly-Pro-Arg-hexamethyleneimine exhibited the highest inhibitory effect on fibrinogen-thrombin clotting.     

Rhodium-catalyzed 1,4-addition of alkenylzirconocene chlorides to electron deficient alkenes

The 1,4-conjugated addition of alkenylzirconocene chloride complexes to α,β-enones, α,β-enoic acid esters, and α,β-enoic acid amides can be efficiently achieved by the use of [RhCl(cod)]₂ catalyst. A high diastereoselectivity (95% yield, 90% de) was obtained through the reaction of α,β-enoic acid amide derived from Oppolzer's sultam and 2-butenoyl chloride, while the use of Evans' chiral oxazolidinone as a chiral auxiliary in place of Oppolzer's sultam gave a poor diastereoselectivity (98% yield, 26% de).     

Stochastic optimization of forward recursive functions

This note solves a finite-horizon stochastic optimization problem with forward recursive criterion through dynamic programming. The forward recursive criterion is wide; it includes additive (discounted), multiplicative (discounted risk-sensitive), minimum and terminal criteria. The basic idea is to apply invariant imbedding method for the stochastic optimization. The method incorporates recursive accumulation process into dynamics by expanding the original state space.     

Vascular dilatory action of the Chinese crude drug. II. Effects of scoparone on calcium mobilization

Further experiments were conducted to examine the effect of scoparone (6,7-dimethoxycoumarin), a coumarin derivative found in the Chinese crude drug "Capillaris Flos," on calcium mobilization. Scoparone does not affect Ca2+ influx through the voltage-dependent channel due to membrane depolarization. Its inhibitory action may be dependent not only on the inhibition of Ca2+ release from sarcoplasmic reticulum but also on the inhibition of extracellular Ca2+ influx through the receptor-operated channel.     

Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6-cycloalkylalkyl derivatives.

A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2- a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-ones 1b--o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b--o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)- [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer.     

Visualization of complexes of Hoechst 33258 and DNA duplexes in solution by atomic force microscopy

Tertiary structure changes in DNA duplexes, induced by Hoechst 33258 binding, have been examined by the use of atomic force microscopy. Besides minor groove binding, which is an established mode of binding for this drug, Hoechst 33258 has now been found to show another binding mode, which causes an unwinding of the duplex. When the drug concentration is as high as 0.5 microg/ml, the Hoechst 33258 molecule seems to function as a clamp for two DNA chains and forms a condensate. The condensate was found to have a toroidal shape. By surveying more than 100 microscopic images of such condensates formed in I microg/ml drug solution, a mechanism of toroidal condensate formation has been proposed.     

High-performance liquid chromatographic procedure for the simultaneous determination of norfloxacin, fenbufen and felbinac in rat plasma

A high-performance liquid chromatographic method for the simultaneous determination of norfloxacin, fenbufen and felbinac extracted from 50 microliters of rat plasma is described. Chromatography was performed on a reversed-phase column with ultraviolet detection. By the present method, quantitative and reproducible determinations were possible for norfloxacin, fenbufen and felbinac over the concentration ranges of 0.2-20, 0.2-120 and 0.4-40 micrograms/ml, respectively. The recoveries of norfloxacin, fenbufen and felbinac added to plasma were nearly 100% with a coefficient of variation of less than 8.0%. This method was found to be applicable to pharmacokinetic studies of each drug after the concomitant administration of norfloxacin and fenbufen.