# Phosphorus-Derived Isatin Hydrazones: Synthesis, Structure, Thromboelastography, Antiplatelet, and Anticoagulation Activity Evaluation

## TL;DR

This paper reports the synthesis and evaluation of new phosphorus-based isatin hydrazones with promising antiplatelet and anticoagulant properties.

## Contribution

The study introduces novel phosphorus-containing isatin hydrazones with superior anti-aggregant activity compared to acetylsalicylic acid.

## Key findings

- Phosphorus-derived isatin hydrazones were synthesized with high yield and purity.
- The Z,syn isomer was confirmed as the predominant form both in solution and in crystals.
- Some derivatives showed better anti-aggregant activity than acetylsalicylic acid in ex vivo models.

## Abstract

A series of new isatin hydrazones bearing phosphorus-containing moiety was synthesized through a simple, high-yield and easy work-up reaction of phosphine oxide (Phosenazide) or phosphinate (2-chloroethyl (4-(dimethylamino)phenyl)(2-hydrazinyl-2-oxoethyl)phosphinate, CAPAH) hydrazides with aryl-substituted isatins. The 31P NMR technique showed that, in most cases, out of 12 examples in solution, the ratio of the two spatial isomers varied from 1:1 to 1:3. Quantum chemical calculations confirmed the predominance of Z,syn form both in the gas phase and in solution. According to X-ray analysis data in crystals, they exist only in Z,syn form too. Most of the phosphine oxide derivatives and 5-methoxy- and 5-bromoaryl phosphinate analogs exhibit anti-aggregant activity at the level of acetylsalicylic acid but inhibit platelet activation processes more effectively. The 5-chloro type phosphinate derivative exhibits anti-aggregant properties more effectively than acetylsalicylic acid under the conditions of the tissue factor (TF)-activated thromboelastography (TEG) model, the ex vivo thrombosis model. Thus, all the obtained results can become the basis for future pharmaceutical developments to create effective anti-aggregation drugs with broad antithrombotic potential.