6660. Nizatidine

Nomenclature

CAS number: 76963-41-2
N-[2-[[[2-[(Dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N′-methyl-2-nitro-1,1-ethenediamine; N-[4-(6-methylamino-7-nitro-2-thia-5-aza-6-heptene-1-yl)-2-thiazolylmethyl]-N,N-dimethylamine; LY-139037; ZE-101; ZL-101; Axid (Lilly); Calmaxid (Lilly); Cronizat (Caber); Distaxid (Norgine); Gastrax (Asche); Nizax (Lilly); Nizaxid (Norgine).
C12H21N5O2S2; mol wt 331.46.
C 43.48%, H 6.39%, N 21.13%, O 9.65%, S 19.35%.

Description and references

Histamine H2-receptor antagonist related to ranitidine, q.v. Prepn: R. P. Pioch, EP 49618; idem, US 4375547 (1982, 1983 both to Eli Lilly). Crystal structure: G. A. Stephenson et al., J. Mol. Struct. 380, 93 (1996). General pharmacology in animals: K. Bemis et al., Arzneim.-Forsch. 39, 240 (1989). Pharmacokinetics and gastric acid suppression in humans: J. T. Callaghan et al., Clin. Pharmacol. Ther. 37, 162 (1985). Voltammetric determn in biological fluids: A. A. Al-Majed et al., J. Pharm. Biomed. Anal. 21, 319 (1999). Determn in pharmaceutical prepns: F. A. El-Yazbi et al. ibid., 31, 1027 (2003). Symposium on pharmacology and clinical studies: Scand. J. Gastroenterol. 22, Suppl. 136, 1-88 (1987). Comprehensive description: T. J. Wozniak, Anal. Profiles Drug Subs. 19, 397-427 (1990). Review of prokinetic activity and clinical use in gastroesophageal reflux disease: E. J. Zarling, Clin. Ther. 21, 2038-2046 (1999).

Chemical structure

Properties

Crystals from ethanol-ethyl acetate, mp 130-132°. Bitter taste; mild sulfur-like odor. Crystal density: 1.324 g/cm3. uv max (methanol): 240, 325 nm (ε 8400, 19600); (water): 260, 314 nm (ε 11820, 15790). pKa1 2.1; pKa2 6.8. Partition coefficient (octanol/water): 0.3 (pH 7.4). Soly (mg/ml): chloroform >100; methanol 50.0-100.0; water 10.0-33.3; isopropanol 3.33-5.0; ethyl acetate 1.0-2.0; benzene, diethyl ether, octanol <0.5. LD50 in mice, rats (mg/kg): 265, >300 i.v.; 1685, 1680 orally (Pioch).

Therapeutic Category

Antiulcerative; gastroprokinetic.

Therapeutic Category (Veterinary)

Gastroprokinetic.

Keywords

Antiulcerative; Histamine H2-Receptor Antagonist; Gastroprokinetic