[2-Amino-oxazoles as potential H-bonding agents in virostatic research. 4. Pharmacokinetics and pharmacologic-toxicologic profile of 2-guanidino-4,5-dipropyloxazole hydrochloride].
Out of the group of 2-amino-oxazoles 1 was found to be the most potent antiviral compound. Following p.o. or s.c. administration to rats, the 14C-labeled 1 was quickly and completely absorbed. The TRA was eliminated mainly via the kidneys and the liver with half-lives between 32 and 42 h. The acute pharmacodynamic effects of 1 were decrease of blood pressure, bradycardia, and inhibition of both gastric emptying and acid secretion. On smooth muscles spasmolytic and alpha-anti-adrenergic actions were predominant. After single administration the following MTD's were determined: 30 (mouse), 20 (rat), 10 mg/kg i.v. (pig), and 500 (mouse, rat), greater than 100 mg/kg p.o. (pig), respectively. In a subchronic toxicity study in rats, oral doses of 1 between 15 and 240 mg/kg given daily for 4 weeks were tolerated without any severe alterations related to the drug.
Hoffmann
H
H
Institut für Mikrobiologie und experimentelle Therapie Jena.
Hillesheim
H G
HG
Amlacher
R
R
Kirchner
E
E
Härtl
A
A
Horn
U
U
Güttner
J
J
Knappe
H
H
Ulbricht
H
H
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010080:Oxazoles / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
C027021:2-guanidino-4,5-di(n-propyl)oxazole; D000998:Antiviral Agents; D010080:Oxazoles
2-Amino-oxazole als potentielle H-Brückenbildner in der Virostatika-Forschung. 4. Mitteilung: Pharmakokinetik und pharmakologisch-toxikologisches Wirkprofil von 2-Guanidino-4,5-dipropyloxazol-hydrochlorid.