References of (1E)-1-ethoxy-N-(3-morpholin-4-yloxadiazol-3-ium-5-yl)methanimidate
Title: Molsidomine
CAS Registry Number: 25717-80-0
CAS Name: N-(Ethoxycarbonyl)-3-(4-morpholinyl)sydnone imine
Synonyms: N-carboxy-3-morpholinosydnonimine ethyl ester; morsydomine
Manufacturers' Codes: SIN-10
Trademarks: Corvaton (Aventis); Corvasal (Aventis); Molsidolat (Aventis); Morial (Takeda); Motazomin (Takeda)
Molecular Formula: C9H14N4O4
Molecular Weight: 242.23
Percent Composition: C 44.63%, H 5.83%, N 23.13%, O 26.42%
Literature 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.
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 l <320 mm. 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).
Melting point: mp 140-141° (toluene)
pKa: pK (100°) 3.0 ± 0.1
Absorption maximum: uv max (CHCl3): 326 nm
Toxicity data: 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)
Therap-Cat: Antianginal.
Keywords: Antianginal.
