イソニコチン酸ヒドラジド

イソニコチン酸ヒドラジド · アルマジド · イソニドリン · ネオキシン · 4-ピリジンカルボン酸ヒドラジド · ヒドラジド · ニドラジド · ペラジド

識別子と物理属性

CAS No.	54-85-3
分子式	C6H7N3O
平均分子量	137.14 g/mol
単同位体質量	137.05891184 g/mol
SMILES	NNC(=O)c1ccncc1
InChIKey	QRXWMOHMRWLFEY-UHFFFAOYSA-N
PubChem CID	3767
ChEMBL	CHEMBL64
ChEBI	CHEBI:6030
EC No.	200-214-6
DTXSID	DTXSID8020755
現地名	イソニコチン酸ヒドラジド

化学・物理的性質

XLogP	-0.7
極性表面積	68
水素結合供与体数	2
水素結合受容体数	3
回転可能結合数	1
重原子数	10
形式電荷	0
複雑度	120
物質分類	Other Uses -> Pharmaceuticals
医薬品	PharmaceuticalsPharmaceuticals -> Listed in ZINC15
pH	pH of a 1% aqueous solution 5.5 to 6.56-8 (50g/l, H2O, 20℃)
SpringerMaterials Properties	Crystal structure
LogP（分配係数）	log Kow = -0.70-0.8-0.5
Color/Form	COLORLESS OR WHITE CRYSTALS, OR A WHITE, CRYSTALLINE POWDERCrystals from alcohol
溶解度	greater than or equal to 100 mg/mL at 77 °F (NTP, 1992)Solubility in alcohol at 25 °C: about 2, in boiling alcohol: about 10%in chloroform: about 0.1%. Practically insoluble in ether, benzene.Sol in methyl ethyl ketone, acetoneIn water, 1.4X10+5 mg/L at 25 °C3.49e+01 g/L125g/リットル14g/100mL(25℃)
引火点	374 °F (NTP, 1992)> 250 °C>250°C
Human Drugs	Breast FeedingLactationMilk, HumanAnti-Infective AgentsAntitubercular AgentsFDA approved drugs -> Active ingredientAntituberculosis medicines
Animal Drugs	EMA approved medicines: Veterinary medicine
Endocrine Disruptors	Potential endocrine disrupting compound
Decomposition	When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
融点	171-173 °C (lit.)
沸点	251.97°C (rough estimate)
密度	1.2620 (rough estimate)
屈折率	1.6910 (estimate)
貯蔵条件	2-8°C
外観・状態	結晶または結晶性粉末
pKa（酸解離定数）	pKa 2.00/3.60/10.8(H2O) (Uncertain)
色	白または無色
臭い	無臭
Merck	14,5186
BRN	119374
BCS Class	1,3
安定性	安定していますが、空気や光に敏感な場合があります。可燃性。強力な酸化剤、クロラール、アルデヒド、ヨウ素、鉄塩、次亜塩素酸塩とは相容れない。
主な用途	法医学と毒物学医薬品（低分子化合物）
InChI	1S/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10)
InChIKey	QRXWMOHMRWLFEY-UHFFFAOYSA-N
SMILES	NNC(=O)c1ccncc1
CAS データベース	54-85-3(CAS DataBase Reference)
NISTの化学物質情報	Isoniazid(54-85-3)
EPAの化学物質情報	Isoniazid (54-85-3)

化学的特性

white crystalline powder

安全性と法規制

GHS 分類	WarningH302 (98.5%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P280, P301+P317, P302+P352, P321, P330, P332+P317, P362+P364, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 400 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.DangerH302: Harmful if swallowed [Warning Acute toxicity, oral]
規制情報	4-Pyridinecarboxylic acid hydrazide: Does not have an individual approval but may be used under an appropriate group standard
その他の安全情報	IMAP assessments - 4-Pyridinecarboxylic acid, hydrazide: Environment tier I assessment
火災危険	This chemical is combustible. (NTP, 1992)Combustible. Gives off irritating or toxic fumes (or gases) in a fire.
健康有害性	SYMPTOMS: Symptoms of exposure to this compound include irritation of the skin, peripheral nerve sensory changes, somnolence, anorexia, sweating, respiratory depression, urine changes and toxic psychosis. Other symptoms include dizziness, paresthesias, fatal hepatitis, metabolic acidosis, convulsions and coma. It can cause headache, muscle twitching, deafness, polyneuritis, paralysis and pyridoxine deficiency. It can also cause nausea, vomiting, atropinic signs such as mydriasis, brightly colored lights and other visual hallucinations, tachycardia, peripheral neuropathy, other central nervous system reactions, stupor, exhaustion, urinary retention, liver damage, bone marrow damage and death. Exposure may cause fatigue, weakness, malaise, toxic encephalopathy, optic neuritis, optic atrophy, memory impairment, epigastric distress, elevated serum transaminases (SGOT, SGPT), bilirubinemia, bilirubinuria, jaundice, agranulocytosis hemolytic anemia, sideroblastic anemia, aplastic anemia, thrombocytopenia, eosinophilia, fever, skin eruptions (morbilliform, maculopapular, purpuric or exfoliative), lymphadenopathy, vasculitis, pellagra, hyperglycemia, gynecomastia, rheumatic syndrome, systemic lupus erythematosus-like syndrome, blurred vision, respiratory distress, central nervous system depression, severe and intractable seizures and acetonuria. Exposure may also cause gastrointestinal effects, liver necrosis, slight euphoria, irritability, nervousness, insomnia, excessive dreaming and giddiness. Other symptoms include peripheral neuritis, burning of the feet, reduction of central vision and papilledema. Hyperreflexia, vertigo, ataxia, tinnitus, hepatic reactions, hypersensitivity reactions and lethargy may occur. Constipation, difficulty in starting urination, dryness of the mouth, mood-elevating effect and mental disturbances, ranging from minor personality changes to major mental derangements. This compound may also cause skin rash, urticaria, arthritic symptoms such as back pain, bilateral proximal interphalangeal joint involvement, arthralgia of the knees, elbows and wrists and "shoulder-hand" syndrome

用途

解説

イソニアジド，イソニコチン酸ヒドラジド isonicotic acid hydorazid(INAH)ともいう。ストレプトマイシンや PASとともに第1次抗結核剤であるが，これらよりも抗結核菌作用が強く，これらと交差耐性も示さない。作用機序は明らかでないが，結核菌の代謝拮抗物質として作用すると考えられている。消化管からの吸収はよく，髄液を含めてすべての臓器に分布する。毒性は低く，副作用も少い。大量投与すれば，中枢神経興奮症状 (不穏，不眠，けいれん，反射亢進，異常感覚など) ，末梢神経炎，口渇，排尿困難などの副作用がみられる。1898年に化学物質として合成され、1952年に結核菌に対して有効なことが発表された。抗結核剤のうち作用のもっとも強力なものの一つで、パス（パラアミノサリチル酸）、ストレプトマイシンとの三者併用が結核の代表的治療法であった。この三者のうちイソニアジドに耐性菌ができにくかったが、現在では耐性菌が発現し、使用量は徐々に減ってきている。粉末、錠剤があり、おもに内服で用いられるが、水に溶けやすいため注射薬もある。常用量は1日0.2～0.5グラム。

説明

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.

使用

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.

一般的な説明

Odorless colorless or white crystals or white crystalline powder. Taste is slightly sweet at first and then bitter. pH (1% aqueous solution) 5.5-6.5. pH (5% aqueous solution) 6-8.

製法・合成法

純化方法

Crystallise isoniazide from 95% EtOH and dry it in a vacuum. [Beilstein 22 III/IV 545, 22/2 V 219.]