Isoniazid

Base Information

• Chemical Name: Isoniazid
• CAS No.: 54-85-3
• Deprecated CAS: 37271-10-6,41466-07-3,62229-51-0,7640-37-1,62229-51-0,7640-37-1
• Molecular Formula: C6H7N3O
• Molecular Weight: 137.141
• Hs Code.: 29333999
• European Community (EC) Number: 200-214-6
• ICSC Number: 1258
• NSC Number: 757078,9659
• UNII: V83O1VOZ8L
• DSSTox Substance ID: DTXSID8020755
• Nikkaji Number: J1.371D
• Wikipedia: Isoniazid
• Wikidata: Q423169
• NCI Thesaurus Code: C600
• RXCUI: 6038
• Metabolomics Workbench ID: 43209
• ChEMBL ID: CHEMBL64
• Mol file: 54-85-3.mol

Synonyms:Acid Vanillylidenehydrazide, Isonicotinic;Ftivazide;Hydrazide, Isonicotinic Acid;Isonex;Isoniazid;Isonicotinic Acid Hydrazide;Isonicotinic Acid Vanillylidenehydrazide;phthivazid;Phthivazide;Tubazide;Vanillylidenehydrazide, Isonicotinic Acid

Chemical Property of Isoniazid

Chemical Property:

• Appearance/Colour: white crystalline powder
• Melting Point: 171-173 °C(lit.)
• Refractive Index: 1.577
• Boiling Point: 251.97°C (rough estimate)
• PKA: pKa 2.00/3.60/10.8(H2O) (Uncertain)
• Flash Point: >250°C
• PSA: 68.01000
• Density: 1.244 g/cm³
• LogP: 0.77630
• Storage Temp.: Refrigerator
• Sensitive.: Air Sensitive
• Solubility.: 125g/l
• Water Solubility.: 14 g/100 mL (25 ºC)
• XLogP3: -0.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 137.058911855
• Heavy Atom Count: 10
• Complexity: 120

Purity/Quality:

99% ^*data from raw suppliers

Isoniazid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-38-40-36/37/38
• Safety Statements: 37-36/37/39-26

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Other Uses -> Pharmaceuticals
• Drug Classes: Antituberculosis Agents
• Canonical SMILES: C1=CN=CC=C1C(=O)NN
• Recent ClinicalTrials: Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation
• Recent EU Clinical Trials: Impact of LTBI treatment on glucose tolerance and chronic inflammation
• Inhalation Risk: Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly when dispersed, especially if powdered.
• Effects of Short Term Exposure: The substance may cause effects on the nervous system, eyes and kidneys. Exposure at high levels could cause death. Exposure could cause convulsions. The substance is irritating to the eyes, skin and respiratory tract.
• Effects of Long Term Exposure: The substance may have effects on the central nervous system and liver. This may result in tissue lesions and impaired functions. Repeated or prolonged contact with skin may cause dermatitis.
• Description: Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycolic acid, an important component of the cell membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the cause of the selective toxicity of the drug with respect to these microorganisms. Mutants that are resistant to isoniazid are rarely seen in nature, and in a spontaneously growing population of tuberculous bacillus there is approximately one mutant in every 105 –106 organisms. Large populations of microorganisms of the order 109 –1010 bacilli in the pulmonary cavities contain a significant number of resistant mutants. If only isoniazid is taken during treatment, an increased number of mutants will be observed and they will eventually become the dominant phenotype. The transformation from sensitive to nonsensitive microorganisms during treatment is called secondary or acquired resistance, which can originate over the course of a few weeks. Isoniazid is the most important drug for treating pulmonary and nonpulmonary forms of tuberculosis. It is active against both intracellular and extracellular organisms. In order to prevent secondary resistance, isoniazid should be used with other effective drugs (usually rifampin). Synonyms of this drug are tubazid, andrazide, niazid, piridizin, and many others. Isoniazid is an antibiotic that acts as a prodrug, being converted by bacterial catalase-peroxidases to form isonicotinic acyl-NADH complex, which inhibits mycolic acid biosynthesis. It is effective against several species of Mycobacterium, including M. tuberculosis.
• Uses: Isoniazid is an antimicrobial used for the prevention of tuberculosis infection or used concurrently with another agent for the treatment of tuberculosis infection. Rifampin, pyrazinamide, or both of these agents are commonly used with isoniazid. Isoniazid is the only Food and Drug Administration approved drug to treat latent tuberculosis in order to prevent it from becoming active. antibacterial, tuberculostatic Antibiotic for treatment of Mycobacterium tuberculosis, inhibits mycolic acid biosynthesis. Metabolized by hepatic N-acetyltransferase (NAT) and cytochrome P450 2E1 (CYP2E1) to form hepatotoxins. Sele ctively induces expression of CYP2E1. Reversibly inhibits CYP2C19 and CYP3A4 activities, and mechanistically inactivates CYP1A2, CYP2A6, CYP2C19 and CYP3A4 at clinically relevant concentrations. Antib acterial (tuberculostatic). For the treatment of all forms of tuberculosis in which organisms are susceptible.
• Indications: Isoniazid (isonicotinic acid hydrazide, or INH) is the most active drug for the treatment of tuberculosis caused by susceptible strains. It is a synthetic agent with a structural similarity to that of pyridoxine.
• Therapeutic Function: Antitubercular
• Biological Functions: Its action is bactericidal against replicating organisms, but it appears to be only bacteriostatic at best against semidormant and dormant populations. After treatment with INH, M . tuberculosis loses its acid fastness, which may be interpreted as indicating that the drug interferes with cell wall development.
• Clinical Use: Isonicotinic acid hydrazide, isonicotinyl hydrazide, or INH(Nydrazid) occurs as a nearly colorless crystalline solid thatis very soluble in water. It is prepared by reacting the methylester of isonicotinic acid with hydrazine.Isoniazid is a remarkably effective agent and continuesto be one of the primary drugs (along with rifampin, pyrazinamide,and ethambutol) for the treatment of tuberculosis.It is not, however, uniformly effective against all formsof the disease. The frequent emergence of strains of the tuberclebacillus resistant to isoniazid during therapy wasseen as the major shortcoming of the drug. This problemhas been largely, but not entirely, overcome with the use ofcombinations.The activity of isoniazid is manifested on the growing tuberclebacilli and not on resting forms. Its action, which isconsidered bactericidal, is to cause the bacilli to lose lipidcontent by a mechanism that has not been fully elucidated.The most generally accepted theory suggests that the principaleffect of isoniazid is to inhibit the synthesis of mycolicacids, high–molecular-weight, branched β-hydroxyfatty acids that constitute important components of the cellwalls of mycobacteria. Isoniazid is among the safest and most active mycobactericidal agents. It is considered the primary drug for use in all therapeutic and prophylactic regimens for susceptible tuberculosis infections. It is also included in the first-line drug combinations for use in all types of tuberculous infections. Isoniazid is preferred as a single agent in the treatment of latent tuberculosis infections in high-risk persons having a positive tuberculin skin reaction with no radiological or other clinical evidence of tuberculosis. Mycobacterium kansasii is usually susceptible to isoniazid, and it is included in the standard multidrug treatment regimen. Tuberculosis (intensive and continuation phases) Prevention of primary tuberculosis in close contacts and reactivation disease in infected but healthy persons (monotherapy)
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: increased risk of hepatotoxicity with rifampicin. Antiepileptics: metabolism of carbamazepine, ethosuximide and phenytoin inhibited (enhanced effect); also with carbamazepine, isoniazid hepatotoxicity possibly increased.

Technology Process of Isoniazid

There total 32 articles about Isoniazid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.1%

butyl isonicotinate (13841-66-2) → isoniazid (54-85-3,7640-37-1)

Guidance literature:

With hydrazine hydrate; at 60 ℃; for 4h;

DOI:10.1007/BF00777388

Reference yield: 97.34%

isonicotinamide (1453-82-3) → isoniazid (54-85-3,7640-37-1)

Guidance literature:

With hydrazine; at 115 ℃; for 4h;

Reference yield: 97.3%

isonicotinic acid ethylester (1570-45-2) → isoniazid (54-85-3,7640-37-1)

Guidance literature:

With hydrazine hydrate; In methanol; for 0.0333333h; Microwave irradiation;

upstream raw materials:

pyridine-4-carbonitrile

pyridine-4-carboxylic acid

isonicotinic acid ethylester

isonicotinamide

Downstream raw materials:

isonicotinic acid-[2-(tetra-O-acetyl-β-D-glucopyranosyloxy)-benzylidenehydrazide]

3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine

2-pyridylcarboxaldehyde isonicotinoyl hydrazone

(E)-N′-(pyridin-4-ylmethylene) isonicotinohydrazide

Refernces

Synthesis and spectroscopic properties of Ni(II) complexes of some aroyl hydrazone ligands with 2,6-diacetyl pyridine monooxime: X-ray crystal structure of the salicyloylhydrazone Ni(II) complex

10.1016/j.ica.2010.05.009

The study focuses on the synthesis and characterization of five new Ni(II) complexes with aroyl hydrazone ligands derived from 2,6-diacetyl pyridine monooxime. The complexes were found to have a distorted octahedral N4O2 coordination environment around the Ni(II) ion, with the ligands coordinating through the pyridine nitrogen, imino-hydrazone nitrogen, and the deprotonated oxygen of the hydrazone moiety. The uncoordinated iminooxime groups and the orthogonal orientation of the CH3–C@N–OH groups relative to the adjacent pyridine rings were observed. The ligands and their corresponding Ni(II) complexes exhibited luminescence, with the complexes showing a lower quantum yield compared to the free ligands. The study also includes the X-ray crystal structure of the Ni(II) salicyloylhydrazone complex, which revealed details about the molecular structure and hydrogen bonding interactions in the crystal lattice. The research provides insights into the coordination chemistry of aroyl hydrazone ligands and their potential applications in areas such as pharmaceuticals and materials science.

Antimycobacterial activity of novel 1,2,4-oxadiazole-pyranopyridine/ chromene hybrids generated by chemoselective 1,3-dipolar cycloadditions of nitrile oxides

10.1016/j.bmc.2011.04.033

This study investigates the synthesis and antimycobacterial activity of novel hybrid compounds against Mycobacterium tuberculosis (MTB). The study employs a chemoselective 1,3-dipolar cycloaddition reaction to generate 1,2,4-oxadiazole-pyranopyridine and 1,2,4-oxadiazole-chromene hybrids from 2-aminopyranopyridine-3-carbonitriles and 2-aminochromene-3-carbonitriles, respectively. The synthesized compounds were evaluated for their in vitro antimycobacterial activity against MTB H37Rv strain. The results revealed that the 1,2,4-oxadiazole-pyranopyridine hybrids exhibited enhanced activity compared to the 1,2,4-oxadiazole-chromene hybrids. Notably, compound 5h demonstrated superior potency, being 1.2, 15.2, and 24.6 times more active than the standard drugs isoniazid, ciprofloxacin, and ethambutol, respectively.