Quinidine
Title: Quinidine
CAS Registry Number: 56-54-2
CAS Name: (9S)-6¢-Methoxycinchonan-9-ol
Additional Names: a-(6-methoxy-4-quinolyl)-5-vinyl-2-quinuclidinemethanol; conquinine; pitayine; b-quinine
Molecular Formula: C20H24N2O2
Molecular Weight: 324.42
Percent Composition: C 74.04%, H 7.46%, N 8.63%, O 9.86%
Literature References: A dextrorotatory stereoisomer of quinine, q.v. Present in cinchona barks to the extent of 0.25-3.0%. Found in quinine sulfate mother liquors. Review of structural elucidation and early synthetic studies: R. B. Turner, R. B. Woodward, in The Alkaloids vol. 3, 1-63 (1953). Configuration: Prelog, Zalán, Helv. Chim. Acta 27, 535 (1944); Prelog, Häfliger, ibid. 33, 2021 (1950); Roth, Pharmazie 16, 257 (1961). Crystal and molecular structure: R. Doherty et al., J. Pharm. Sci. 67, 1698 (1978). Rotatory dispersion studies: Lyle, Gaffield, Tetrahedron Lett. 1963, 1371. Prepn by isomerization of quinine: W. E. Doering et al., J. Am. Chem. Soc. 69, 1700 (1949). Total synthesis: J. Gutzwiller, M. Uskokovic, ibid. 92, 204 (1970); eidem, Helv. Chim. Acta 56, 1494 (1973); eidem, J. Am. Chem. Soc. 100, 576 (1978). Toxicity data: C. Turba et al., Arzneim.-Forsch. 18, 1127 (1968); K. Dietmann et al., ibid. 27, 589 (1977). Comprehensive description of the sulfate: M. A. Loutfy et al., Anal. Profiles Drug Subs. 12, 483-546 (1983). Clinical evaluation in severe malaria: R. E. Phillips et al., N. Engl. J. Med. 312, 1273 (1985). Review of pharmacology and clinical efficacy in cardiac arrhythmias: J. W. Mason, L. M. Hondeghem, Ann. N.Y. Acad. Sci. 432, 162-176 (1984); A. R. Leon, J. D. Merlino, Heart Dis. Stroke, 2, 407-413 (1993).
Properties: Triboluminescent. mp 174-175° after drying of solvated crystals. [a]D15 +230° (c = 1.8 in chloroform), [a]D17 +258° (alc), [a]D17 +322° (c = 1.6 in 2M HCl). pK1 (20°) 5.4; pK2 10.0. Blue fluorescence in dil H2SO4. The uv absorption spectrum is identical with that of quinine. One gram dissolves in about 2000 ml cold, 800 ml boiling water, 36 ml alcohol, 56 ml ether, 1.6 ml chloroform; very sol in methanol. Practically insol in petr ether. LD50 in rats (mg/kg): 30 i.v., 263 orally (Dietmann).
Melting point: mp 174-175° after drying of solvated crystals
pKa: pK1 (20°) 5.4; pK2 10.0
Optical Rotation: [a]D15 +230° (c = 1.8 in chloroform); [a]D17 +258° (alc); [a]D17 +322° (c = 1.6 in 2M HCl)
Toxicity data: LD50 in rats (mg/kg): 30 i.v., 263 orally (Dietmann)
 
Derivative Type: Hemipentahydrate
Properties: Prisms from dil alcohol, loses ½ H2O in air, mp ~168°.
Melting point: mp ~168°
 
Derivative Type: Hydrogen sulfate tetrahydrate
CAS Registry Number: 6151-39-9
Additional Names: Quinidine bisulfate
Trademarks: Chinidin-Duriles (Astra); Kiditard (Belga); Kinichron (Biochimica); Kinidin Durules (Astra); Quiniduran (Teva)
Molecular Formula: C20H24N2O2.H2SO4.4H2O
Molecular Weight: 494.56
Percent Composition: C 48.57%, H 6.93%, N 5.66%, O 32.35%, S 6.48%
Properties: Rods, sol in 8 parts water with blue fluorescence.
 
Derivative Type: Sulfate dihydrate
CAS Registry Number: 6591-63-5; 50-54-4 (anhydrous)
Trademarks: Cin-Quin (Rowell); Quinidex Extentabs (Robins); Quinicardine (Procter & Gamble); Quinora (Key)
Molecular Formula: (C20H24N2O2)2.H2SO4.2H2O
Molecular Weight: 782.94
Percent Composition: C 61.36%, H 6.95%, N 7.16%, O 20.44%, S 4.10%
Properties: White, very bitter, odorless, fine crystals, frequently cohering in masses. Darkens on exposure to light. Does not lose all of its water below 120°. [a]D25 ~+212° (95% alcohol); ~+260° (dil HCl). pKa 4.2, 8.8. pH (1% aq soln): 6.0-6.8. One gram dissolves in about 90 ml water, 15 ml boiling water, 10 ml alcohol, 3 ml methanol, 12 ml chloroform. Insol in ether, benzene. Protect from light. LD50 in mice, rats (mg/kg): 700, 455.8 orally; 83, 56 i.v. (Turba).
pKa: pKa 4.2, 8.8
Optical Rotation: [a]D25 ~+212° (95% alcohol); ~+260° (dil HCl)
Toxicity data: LD50 in mice, rats (mg/kg): 700, 455.8 orally; 83, 56 i.v. (Turba)
 
Derivative Type: Gluconate
CAS Registry Number: 7054-25-3
Additional Names: Gluconic acid quinidine salt
Trademarks: Duraquin (Warner-Chilcott); Quinaglute (Berlex)
Molecular Formula: C26H36N2O9
Molecular Weight: 520.57
Percent Composition: C 59.99%, H 6.97%, N 5.38%, O 27.66%
Properties: Crystals, mp 175-176.5°. Sol in 9 parts water, 60 parts alcohol.
Melting point: mp 175-176.5°
 
Derivative Type: Polygalacturonate
CAS Registry Number: 7681-28-9
Trademarks: Cardioquin (Purdue Frederick); Galactoquin (Mundipharma); Naticardina (Viatris)
Literature References: (C20H24N2O2.C6H10O7.H2O)x. Prepn: A. Halpern et al., Am. J. Pharm. 130, 190 (1958). Pharmacology: A. Halpern et al., Antibiot. Chemother. 9, 97 (1959).
Properties: Amorphous powder, mp 180° (dec). Anhydr product is insol in methanol, ethanol, chloroform, ether, acetone, dioxane. Soly in hot 40% methanol or ethanol: 12%; in water at 25°: ~2%. LD50 in rats, mice (mg/kg): 3200 ± 350, 2680 ± 210 orally (Halpern, 1959).
Melting point: mp 180° (dec)
Toxicity data: LD50 in rats, mice (mg/kg): 3200 ± 350, 2680 ± 210 orally (Halpern, 1959)
 
Therap-Cat: Antiarrhythmic (class IA); antimalarial.
Therap-Cat-Vet: Antiarrhythmic.
Keywords: Antiarrhythmic; Antimalarial.

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