5186. Isoniazid

Nomenclature

CAS number: 54-85-3
4-Pyridinecarboxylic acid hydrazide; isonicotinic acid hydrazide; isonicotinoylhydrazine; isonicotinylhydrazine; INH; rimitsid; tubazid; RP-5015; FSR-3; Isonex (Pfizer); Isotamine (Valeant); Isozid (Fatol); Neoteben (Bayer); Nicizina (Pharmacia); Nicozid (Piam); Nydrazid (BMS); Rimifon (Pharmion); tebesium (Pharma Wernigerode); Tibinide (Recip); Valifol (Valdecasas).
C6H7N3O; mol wt 137.14.
C 52.55%, H 5.14%, N 30.64%, O 11.67%.

Description and references

Prepn: Meyer, Mally, Monatsh. Chem. 33, 400 (1912); Lock, Pharm. Ind. 14, 366 (1952); Urbanski et al., Rocz. Chem. 27, 161 (1953); Gasson, US 2830994 (1958 to Distillers). Compositions for combating tuberculosis: H. H. Fox, US 2596069 (1952 to Hoffmann-La Roche). Pharmacokinetics: W. W. Weber, D. W. Hein, Clin. Pharmacokinet. 4, 401 (1979). Mechanism of action study: K. Johnsson et al., J. Am. Chem. Soc. 117, 5009 (1995). Toxicity data: E. H. Jenney, C. C. Pfeiffer, J. Pharmacol. Exp. Ther. 122, 110 (1958). Evaluation of carcinogenic risk: IARC Monographs 4, 159 (1974). Comprehensive description: G. A. Brewer, Anal. Profiles Drug Subs. 6, 183-258 (1977). Clinical trial in HIV-positive patients: J. W. Pape et al., Lancet 342, 268 (1993). Review of use in prevention and treatment of TB: American Thoracic Society, Am. Rev. Respir. Dis. 134, 355-363 (1986); T. J. Jordan et al., ibid. 144, 1357-1360 (1991).

Chemical structure

Properties

Crystals from alc, mp 171.4°. uv max (water): 266 nm (E1%1cm 378); (0.01N HCl): 265 nm (E1%1cm ≈420). Soly in water at 25°: about 14%; at 40°: about 26%; in alc at 25°: about 2%, in boiling alc: about 10%; in chloroform: about 0.1%. Practically insol in ether, benzene. pH of a 1% aq soln 5.5 to 6.5. Aqueous solns may be sterilized at 120° for 30 min. LD50 in mice (mg/kg): 151 i.p., 149 i.v. (Jenney, Pfeiffer).

Derivative

4-Aminosalicylate.

Nomenclature

CAS number: 2066-89-9
Pasiniazide; GEWO-399.
C13H14N4O4; mol wt 290.27.
C 53.79%, H 4.86%, N 19.30%, O 22.05%.

Description and references

An equimolecular salt produced by dissolving the components in hot dil alc, followed by cooling and evapn: Charonnat, Boime, Compt. Rend. 236, 2140 (1953). Prepn: CH 303085 (1955 to Hoffmann-La Roche).

Properties

Yellow crystals from methanol or ethanol, mp 142-144°. Sparingly sol in water. uv max 272, 303 nm (E1%1cm 550, 445).

Derivative

Methanesulfonate.

Nomenclature

CAS number: 13447-95-5
4-Pyridinecarboxylic acid 2-(sulfomethyl)hydrazide; methaniazide.
C7H9N3O4S; mol wt 231.23.
C 36.36%, H 3.92%, N 18.17%, O 27.68%, S 13.87%.

Description and references

Prepn: Logemann, US 2759944 (1956 to Carlo Erba).

Properties

Crystals, dec 187-189°.

Derivative

Methanesulfonate sodium.

Nomenclature

CAS number: 3804-89-5
Sodium isonicotinylhydrazide methanesulfonate.
C7H8N3NaO4S; mol wt 253.21.
C 33.20%, H 3.18%, N 16.59%, Na 9.08%, O 25.27%, S 12.66%.

Properties

Yellow crystals from water, dec 164-167°.

Therapeutic Category

Antibacterial (tuberculostatic).

Therapeutic Category (Veterinary)

Antibacterial (tuberculostatic); anti-actinomycotic agent.

Keywords

Antibacterial (Tuberculostatic)