Synthesis and Myorelaxant Activity of 1,3-Bis(5-ammoniopentyl)-6-methyluracil Dihalides.

Zobov, V.; Petrov, K.; Aslyamova, A.; Berezinsky, L.; Reznik, V.; Akamsin, V.; Galyametdinova, I.; Giniyatullin, R.

A series of 1,3-bis(5-ammoniopentyl)-6-methyluracil dihalides with the anticholinesterase type of activity have been synthesized and characterized with respect to toxicity and myorelaxant activity. The obtained compounds exhibit high toxicity with respect to mice and belong to the class of low/practically zero toxicity with respect to daphnia. Under conditions of functional loading (treadmill running test) in mice, the compounds with small-volume electron-acceptor substitutes (F, NO2, CN, CH2 OCH3, C(O)OCH3 etc.) at the quaternary nitrogen atoms in the benzyl radical are more effective (upon intraperitoneal injection) and safer than the reference drugs (proserine and BW284c51) and induce the development of a clearly pronounced myorelaxant effect with a duration of no less than 1 day with ED50 = 0.04 – 0.09 µ-M/kg and LD50/ED50 up to 56.25.

HALIDES; URACIL; HETEROCYCLIC compounds; PYRIMIDINES; TOXICOLOGY

Pharmaceutical Chemistry Journal, 2005, Vol 39, Issue 4, p179

0091-150X

Academic Journal

10.1007/s11094-005-0112-1