6234. Molsidomine

Nomenclature

CAS number: 25717-80-0
N-(Ethoxycarbonyl)-3-(4-morpholinyl)sydnone imine; N-carboxy-3-morpholinosydnonimine ethyl ester; morsydomine; SIN-10; Corvaton (Aventis); Corvasal (Aventis); Molsidolat (Aventis); Morial (Takeda); Motazomin (Takeda).
C9H14N4O4; mol wt 242.23.
C 44.63%, H 5.83%, N 23.13%, O 26.42%.

Description and references

Coronary vasodilator; member of a class of non-benzene aromatic, heterocyclic and mesoionic type of compounds previously unknown in the pharmaceutical industry. Developmental work on sydnone imines: Brookes, Walker, J. Chem. Soc. 1957, 4409. Prepn: K. Masuda et al., JP 70 6265; eidem, US 3769283 (1970, 1973 both to Takeda); eidem, Chem. Pharm. Bull. 19, 72 (1971). Stability studies: Asahi et al., ibid. 19, 1079 (1971). Pharmacological studies: Kikuchi et al., Jpn. J. Pharmacol. 20, 102, 187, 253 (1970); Hashimoto et al., Arzneim.-Forsch. 21, 1329 (1971); T. Nakaguchi et al., Toho Igakkai Zasshi 17, 26 (1970). Metabolism: S. Tanayama et al., Xenobiotica 4, 175 (1974). Pharmacokinetics: R. Bergstrand et al., Eur. J. Clin. Pharmacol. 27, 203 (1984). Clinical trial in angina pectoris: P. A. Majid et al., N. Engl. J. Med. 302, 1 (1980); in hypertension: J. Melei et al., Eur. J. Clin. Pharmacol. 18, 231 (1980). Synergism with penbutolol in angina pectoris: A. E. Balestrini et al., ibid. 27, 1 (1984). Review of pharmacology: R.-E. Nitz, V. B. Fiedler, Pharmacotherapy 7, 28 (1987). Review: Jpn. Med. Gaz. 8(9), 10 (1971); E. Bassenge, W. R. Kukovetz in New Drugs Annual: Cardiovascular Drugs Vol. 2, A. Scriabine, Ed. (Raven Press, New York, 1984) pp 177-191.

Chemical structure

Properties

Colorless crystals or white cryst powder, practically tasteless and odorless, mp 140-141° (toluene). Freely sol in CHCl3. Sol in dil HCl, ethanol, ethyl acetate, methanol; sparingly sol in water, acetone, benzene. Very slightly sol in ether, petr ether. pK (100°) 3.0 ± 0.1. Most stable in aq solns pH 5-7; least stable in very alkaline solns. uv max (CHCl3): 326 nm. Sensitive to light of λ <320 mμ. LD50 in male, female mice, male, female rats (mg/kg): 780, 750, 1380, 1350 s.c.; 860, 800, 830, 760 i.v.; 700, 760, 1250, 1250 i.p.; 830, 840, 1050, 1200 orally (Nakaguchi).

Therapeutic Category

Antianginal.

Keywords

Antianginal