Antiradiation agents. Substituted 2-pyridyloxy and 2-quinolyloxy derivatives of S-2-(alkyamino)ethyl hydrogen thiosulfates and 3-alkylthiazolidines and substituted 2-pyridyloxy derivatives of 2-(alkylamino)ethyanethiols and corresponding disulfides

Journal Article · Sun Apr 01 04:00:00 EST 1973 · J. Med. Chem., v. 16, no. 4, pp. 319-327

OSTI ID:4365399

Westland, R D; Cooley, Jr, R A; Holmes, J L; Hong, J S; Lin, M H; Zwiesler, M L; Grenan, M M

Substituted 2-pyridyloxy and 2-quinolyloxy derivatives of S- 2(alkylannino)ethyl hydrogen thiosulfates, 3-alkylthiazolidines, and substituted 2-pyridyloxy derivatives of 2- (alkylamino)ethanethiols and corresponding disulfides were synthesized as antiradiation agents by the appropriate aziridine ring-opening reactions of substituted 2-{STA(1-aziridinyl)alkyl!oxy}pyridines and -quinolines. 5Substituted 2-chloropyridines and substituted 2-chloroquinolines were prepared for heterocyclic ether-forming reactions by treatment with the Na salts of 1-aziridinealkanols to give the aziridinylalkyloxy derivatives. 5-Halo- 2-pyridyl ethers resulted in the highest antiradiation activity regardless of route of administration or type of sulfur-coveringg group. S-2- ({5-STA(5-Chloro- 2-pyridyl)oxy!-pentyl}amino)ethyl hydrogen thiosulfate and S-2- ({5-STA (3,5dichloro-2-pyridyl)oxy! pentyl}amino)ethyl hydrogen thiosulfate afforded 87% survival of mice in the 30-day test at 19 (1/12 of LD/sub 50/ dose) and 12.5 mg/ kg ip (1/14 of LD/sub 50/ dose), respectively. In view of the dearth of agents effective perorally, remarkably good radioprotection was found on oral administration of thiazolidines substituted in the 3 position with 5-halo-2- {pyridyloxypentyl or -hexyl groups; 5-chloro- and 5-iodo-2-{STA6-(3- thiazolidinyl)hexyl! oxy}pyridine hydrochlorides resulted in survival rates of 73% at 150 mg/kg po (0.25 of LD/sub 50/ dose) and 93% at 300 mg/kg po (0.5 of LD/ sub 50/ dose), respectively. (auth)

• Research Organization: Parke, Davis and Co., Ann Arbor, MI
• NSA Number: NSA-29-008010
• OSTI ID: 4365399
• Journal Information: J. Med. Chem., v. 16, no. 4, pp. 319-327, Journal Name: J. Med. Chem., v. 16, no. 4, pp. 319-327; ISSN JMCMA
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

*DISULFIDES-- RADIOSENSITIVITY EFFECTS
*THIOLS-- RADIOSENSITIVITY EFFECTS
*THIOSULFATES-- RADIOSENSITIVITY EFFECTS
CHEMICAL PREPARATION
CHEMICAL REACTIONS
HETEROCYCLIC COMPOUNDS
MICE
N40210 --Chemistry--Inorganic
Organic
& Physical Chemistry--Chemical & Physiochemical Properties
N48510 --Life Sciences--Radiation Effects on Animals--Man
N48520* --Life Sciences--Radiation Effects on Animals-- Vertebrates
ORGANIC CHLORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIATION PROTECTION
RADIOPROTECTIVE SUBSTANCES RADIOSENSITIVITY EFFECTS