Synthesis of Potential Prophylactic Agents Against Cyanide Intoxication
Abstract
The goal of the propose research is to provide prophylaxis against cyanide through its sequestration by covalent bond formation. Three strategies were pursued: (1) sulfur-rich compounds which could serve as sulfane sulfur donors to rhodanese and other sulfur transferases; (2) compounds containing multiple carbonyl moieties, including analogs of pyruvate and alpha- ketoglutarate, which can bind cyanide through cyanohydrin formation; and (3) additional classes of compounds that can directly react with cyanide, such as (i) N-alkoxy and N-alkylthio heterocycles, and (ii) phthalocyanines and porphyrins. During this report period we prepared examples of all compound types just described. The 148 new compounds submitted this period were distributed among these compound classes as follows: sulfur-rich species, 55; polycarbonyl compounds, 39; nitrogenous heterocycles, 40; and metal complexes, 9. Some of these compounds contained multiple functionality that could react with cyanide. One of the sulfur compounds was prepared at the request of the CO and was a re-submission of an additional quantity of a previously submitted sample which had displayed positive biological results during screening (SoRI 7638; WR 268831). We have received biological testing data for 96 compounds during this same period, and now have demonstrated activity in three of our four primary target classes (no phthalocyanines have been tested for efficacy at this point). Of the screened compounds, five were found to have potential as an improved pretreatment for NaCN poisoning, with many additional possibilities as yet unscreened. Anticyanide agents, Polysulfides, Sulfurtransferases(Rhodanese), Cyanohydrin formation, Compounds reactive toward cyanide, Cyanide removal through covalent bonding.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 06, 1993
- Accession Number
- ADB176400
Entities
People
- James R. Piper
Organizations
- Southern Research