Synthesis and Preliminary Evaluation of a New Quinuclidine Derivative as a Radioprotective Agent

• Published in: Journal of pharmaceutical sciences 1968-10, Vol.57 (10), p.1725-1728
• Main Authors: Shapiro, Warren, Tansy, Martin F., Elkin, Samuel
• Format: Article
• Language: English
• Subjects: 10-Ethano-1-thia-4; 7,10-Ethano-1-thia-4,7-diazaspiro[4.5]decane dihydrochloride—synthesis; 7-diazaspiro[4.5]decane dihydrochloride-synthesis; Animals; Antiradiation activity-quinuclidine derivative; Infrared Rays; IR spectrophotometry-structure; Mice; Quinuclidines - chemical synthesis; Quinuclidines - pharmacology; Quinuclidines - toxicity; Radiation Injuries, Experimental - mortality; Radiation Injuries, Experimental - prevention & control; Radiation-Protective Agents - chemical synthesis; Radiation-Protective Agents - pharmacology; Radiation-Protective Agents - toxicity; Radioprotective agent-quinuclidine derivative; Spectrum Analysis
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600571020

7,10-Ethano-1-thia-4,7-diazaspiro [4.5] decane dihydrochloride was prepared by the condensation of 3-quinuclidone hydrochloride with 2-aminoethanethiol hydrochloride. The compound was shown to have potential radioprotective properties against a lethal dose of X-radiation in mice. Optimum protection was obtained in a group of mice pretreated intraperitoneally with 0.20mg./g. of 7,10-ethano-1-thia-4,7-diazaspiro [4.5] decane dihydrochloride 15min. prior to exposure, where 58.3 percent survived. A toxicity study showed the i.p. LD50 of the compound to be 295mg./kg. with a dose range of 257–339mg./kg. (p < 0.05).