Novel, orally effective cyanide antidotes.
A series of prodrugs of 3-mercaptopyruvate (3-MP), the substrate for the enzyme 3-mercaptopyruvate/cyanide sulfurtransferase (3-MPST) that converts cyanide to the nontoxic thiocyanate, which are highly effective cyanide antidotes, have been developed. These prodrugs of 3-MP are unique in being not only orally bioavailable, but may be administered up to an hour prior to cyanide as a prophylactic agent and are both rapid- or slow-acting when given parenterally.
Nagasawa
Herbert T
HT
Center for Drug Design, University of Minnesota, Minneapolis 55455, USA. nagas001@umn.edu
Goon
David J W
DJ
Crankshaw
Daune L
DL
Vince
Robert
R
Patterson
Steven E
SE
D000284:Administration, Oral; D000818:Animals; D000931:Antidotes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003486:Cyanides / Q000506:poisoning*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000931:Antidotes; D003486:Cyanides; D011355:Prodrugs; C008366:3-mercaptopyruvic acid; D003545:Cysteine