406. Amiloride

Nomenclature

CAS number: 2609-46-3
3,5-Diamino-N-(aminoiminomethyl)-6-chloro-2-pyrazinecarboxamide; N-amidino-3,5-diamino-6-chloropyrazinecarboxamide; N-amidino-3,5-diamino-6-chloropyrazinamide; 1-(3,5-diamino-6-chloropyrazinecarboxyl)guanidine; 1-(3,5-diamino-6-chloropyrazinoyl)guanidine; guanamprazine; amipramidin; amipramizide.
C6H8ClN7O; mol wt 229.63.
C 31.38%, H 3.51%, Cl 15.44%, N 42.70%, O 6.97%.

Description and references

Sodium channel blocker. Prepn: E. J. Cragoe, Jr., BE 639386; idem, US 3313813 (1964, 1967 both to Merck & Co.). NMR study on tautomerism and conformation: R. L. Smith et al., J. Am. Chem. Soc. 101, 191 (1979). Determn by isopotential fluorimetry: J. A. Murillo Pulgarín et al., Analyst 122, 247 (1997). Pharmacology: Baer et al., J. Pharmacol. Exp. Ther. 157, 472 (1967); Baba et al., Clin. Pharmacol. Ther. 9, 318 (1968); Lant et al., ibid. 10, 50 (1969). Metabolism: Weiss et al., ibid. 401. Clinical evaluation in cystic fibrosis: M. R. Knowles et al., N. Engl. J. Med. 322, 1189 (1990); in combination with uridine 5′-triphosphate, q.v.: W. D. Bennett et al., Am. J. Respir. Crit. Care Med. 153, 1796 (1996). Reviews: H. L. Macfie et al., Drug Intell. Clin. Pharm. 15, 94-98 (1981); D. E. Hyams, Int. Congr. Symp. Ser. - R. Soc. Med. 44, 65-73 (1981). Comprehensive description of hydrochloride: D. J. Mazzo, Anal. Profiles Drug Subs. 15, 1-34 (1986). Review of mechanism of action: T. R. Kleyman, et al., Semin. Nephrol. 19, 524-532 (1999).

Chemical structure

Properties

Solid, mp 240.5-241.5°. pKa 8.7.

Derivative

Hydrochloride.

Nomenclature

CAS number: 2016-88-8
C6H8ClN7O.HCl; mol wt 266.09.
C 27.08%, H 3.41%, Cl 26.65%, N 36.85%, O 6.01%.

Properties

mp 293.5°.

Derivative

Hydrochloride dihydrate.

Nomenclature

CAS number: 17440-83-4
MK-870; Amikal (GEA); Midamor (Merck & Co.); Modamide (Merck & Co.).
C6H8ClN7O.HCl.2H2O; mol wt 302.12.
C 23.85%, H 4.34%, Cl 23.47%, N 32.45%, O 15.89%.

Properties

Crystalline solid, dec 285-288°. uv max (water): 212, 285, 362 nm (E1%1cm 642, 555, 617). Freely sol in DMSO, slightly sol in water, isopropanol, ethanol. Practically insol in acetone, chloroform, diethyl ether, ethyl acetate.

Derivative

Hydrochloride dihydrate mixture with hydrochlorothiazide.

Nomenclature

Co-amilozide; Amilco (Norton); Aquaretic (Azupharma); Ecodurex (Sandoz); Hexarese (Durascan); Moduretic (Merck & Co.); Moduretik (Merck & Co.); Normetic (Abbott); Normorix (Nycomed).

Therapeutic Category

Diuretic.

Keywords

Diuretic