化工社化工社 化学情報印刷レポート · 研究参考用
4-アミノサリチル酸
4-アミノサリチル酸 · pアミノサリチル酸 · 4-アミノ-2-ヒドロキシ安息香酸 · P-アミノサリチル酸 · 4‐アミノサリチル酸 · シッフ試薬 · アミノサリチル酸 · 1-アミノ-4-(4-スルファモイルアニリノ)-9,10-ジオキソ-9,10-ジヒドロアントラセン-2-スルホン酸
識別子と物理属性
| CAS No. | 65-49-6 |
|---|---|
| 分子式 | C7H7NO3 |
| 平均分子量 | 153.14 g/mol |
| 単同位体質量 | 153.04259308 g/mol |
| SMILES | Nc1ccc(C(=O)O)c(O)c1 |
| InChIKey | WUBBRNOQWQTFEX-UHFFFAOYSA-N |
| PubChem CID | 4649 |
| ChEMBL | CHEMBL1169 |
| ChEBI | CHEBI:27565 |
| EC No. | 200-613-5 |
| DTXSID | DTXSID2022591 |
| 現地名 | 4-アミノサリチル酸 |
化学・物理的性質
| XLogP | 1.3 |
|---|---|
| 極性表面積 | 83.6 |
| 水素結合供与体数 | 3 |
| 水素結合受容体数 | 4 |
| 回転可能結合数 | 1 |
| 重原子数 | 11 |
| 形式電荷 | 0 |
| 複雑度 | 160 |
| 物質分類 | Nitrogen Compounds -> Aminobenzoic Acids |
| 医薬品 | Pharmaceuticals -> AntibioticsPharmaceuticals -> Listed in ZINC15 |
| pH | PH (SATURATED AQ SOLN): BETWEEN 3 & 3.73.5 (1g/l, H2O, 20℃) |
| SpringerMaterials Properties | Diamagnetic susceptibility |
| LogP（分配係数） | LogP= 1.321.6 |
| 臭い | ODORLESS, OR HAS SLIGHT ACETOUS ODOR |
| Color/Form | MINUTE CRYSTALS FROM ALCWHITE, OR NEARLY WHITE, BULKY POWDERNEEDLES, PLATES FROM ALC-ETHERA reddish-brown crystalline powder is obtained on recrystallization from ethanol-ether. |
| 溶解度 | 1 G SOL IN ABOUT 7 ML WATERSLIGHTLY SOL IN ALC /CALCIUM SALT/PH OF 1% SOLN: ABOUT 7FREELY SOL IN WATER /POTASSIUM SALT/For more Solubility (Complete) data for P-AMINOSALICYLIC ACID (7 total), please visit the HSDB record page.SOL IN DILUTE NITRIC ACID & DILUTE SODIUM HYDROXIDEVirtually insoluble in benzene, choroform, or carbon tetrachloride1.69g/リットル2g/L（20℃） |
| Human Drugs | Breast FeedingLactationMilk, HumanAnti-infective AgentsAntitubercular AgentsFDA approved drugs -> Active ingredient |
| 融点 | 150-151 °C, with effervescenceNEEDLES FROM ALCMP: 115 °C /ETHYL ESTER/150.5 °C135-145 °C (lit.) |
| 蒸気圧 | 0.000004 [mmHg] |
| Physical Description | White or nearly white solidAffected by light and air[Hawley] Beige powder[MSDSonline] |
| 沸点 | 276.03°C (rough estimate) |
| 密度 | 1.3585 (rough estimate) |
| 屈折率 | 1.5500 (estimate) |
| 貯蔵条件 | Keep in dark place,Inert atmosphere,Room temperature |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 3.25(at 25℃) |
| 色 | 無色 |
| Merck | 14,477 |
| BRN | 473071 |
| Specific Activity | 17.6-26.4nmol/min·mg |
| BCS Class | 4/2 |
| 安定性 | 吸湿性 |
| 主な用途 | ペプチド合成 |
| InChI | 1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11) |
| InChIKey | WUBBRNOQWQTFEX-UHFFFAOYSA-N |
| SMILES | Nc1ccc(C(O)=O)c(O)c1 |
| CAS データベース | 65-49-6(CAS DataBase Reference) |
| NISTの化学物質情報 | Aminosalicylic acid(65-49-6) |
| EPAの化学物質情報 | 4-Aminosalicylic acid (65-49-6) |
化学的特性
beige powder
安全性と法規制
| GHS 分類 | WarningH315 (43.5%): Causes skin irritation [Warning Skin corrosion/irritation]P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 69 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 規制情報 | Status: Active Update: 23-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/25234Benzoic acid, 4-amino-2-hydroxy-: 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 - Benzoic acid, 4-amino-2-hydroxy-: Environment tier I assessment |
| 有害性の概要 | Not expected to increase congenital malformations based on animal studies[REPROTOX] Oral LD50 (mouse) = 4000 mg/kg[RTECS] An eye irritantTargets the GI system and liver[MSDSonline] See p-Aminosalicylic acid sodium salt dihydrate. |
| FDA 要件 | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392). |
| Special Reports | A review of the literature on the clinical experience, tolerance and toxicity of mesalamine (5-aminosalicylic acid), aminosalicylic acid (4-aminosalicylic acid) and newer mesalamine based drugs for the treatment of chronic inflammatory bowel disease is presented.[Jarnerot GDrugs 37 (Jan): 73-86 (1989)]The initial therapy and retreatment of pulmonary tuberculosis as well as various complicating factors that may affect treatment decisions are presented. Chemotherapeutic agents used in the treatment of tuberculosis and their dosage regiments are mentioned including isoniazid, ethambutol, rifampin, pyrazinamide, ethionamide, cycloserine, streptomycin, kanamycin, aminosalicylate (aminosalicylic acid), and capreomycin.[Spagnolo SVDrug Therapy 15 (Nov): 91-92, 97-100 (1985)] |
| Hazard Classes and Categories | Skin Irrit. 2 (43.5%) |
| 保管条件 | Store below 90 °C (104 °F), unless otherwise specified by manufacturer. Store in tight, light resistant containers. |
| 処分方法 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| 相互作用 | ...PARA-AMINOSALICYLIC ACID.../INHIBITS METABOLISM OF CHLORAMPHENICOL/PENTOBARBITAL /SRP: CNS DEPRESSION/ IN MICE WAS ENHANCED AFTER PRE-TREATMENT WITH... P-AMINOSALICYLIC ACID. INCR /SRP: CNS DEPRESSION/ APPEARED TO BE DUE TO RELEASE OF PENTOBARBITAL FROM SERUM-PROTEIN BINDING, RESULTING IN HIGHER CEREBRAL CONCN...ADDITIVE & SYNERGISTIC WITH STREPTOMYCINS & ISONIAZID.Probenecid decreases the renal excretion of this agent.For more Interactions (Complete) data for P-AMINOSALICYLIC ACID (19 total), please visit the HSDB record page. |
| 有害作用 | Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation. |
| Human Toxicity Excerpts | SEVERE THERAPEUTIC MISADVENTURES, ALTHOUGH RARE, HAVE INCL...HEPATITIS...METHEMOGLOBINEMIA...Adequate and well-controlled studies in humans have not been done. In one study, an increased malformation rate for ears and limbs, and hypospadias were reported in infants of patients taking aminosalicylates with other antitubercular medications. However, other studies have not found aminosalicylates to be teratogenic. /Aminosalicylates/The literature has been reviewed for contact dermatitis occurring to antituberculosis agents. Of the 12 known drugs, 6 (isoniazid, rifampicin, ethambutol, p-aminosalicylic acid, streptomycin and kanamycin) have been documented by patch test to cause this type of dermatitis in certain individuals. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Aminosalicylic acidvMOST-DILI-concern5Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
| Non-Human Toxicity Excerpts | An N-acetylation polymorphism is described that is expressed toward arylamine carcinogens in tumor target organs of an inbred rat model. High levels ... of arylamine carcinogen N-acetyltransferase activity were observed in kidney, colon, prostate and urinary bladder cytosols derived from Fischer (F-344) inbred rats ... Significantly lower ... levels of arylamine carcinogen N-acetyltransferase activity were observed for corresponding tissue cytosols derived from Wistar-Kyoto inbred rats. Intermediate levels of arylamine carcinogen N-acetyltransferase activity significantly different from both the parental strains were observed in F1 hybrids of the parental strains, consistent with codominant expression of two alleles at a single gene locus. The arylamine substrates exhibiting the acetylator phenotype-dependent N-acetyltransferase activities included ... p-aminosalicylic acid ... Highest levels of arylamine carcinogen N-acetyltransferase were expressed consistently in colon cytosol, but expression of the N-acetylation polymorphism toward arylamine carcinogens was observed in each (kidney, colon, prostate and urinary bladder) of the tumor target organs. The expression of the N-acetylation polymorphism in tumor target organs suggests that the inbred rat model will be useful in assessing the role of acetylator phenotype in arylamine-induced cancers of the colon and prostate.An overview is presented of a selected number of mono-aromatic derivatives and their short-term effects on hepatic fatty acid biosynthesis. The cmpd discussed in this paper are o-hydroxybenzoate ... m-hydroxybenzoate, p-hydroxybenzoate, benzoate, p-t-butylbenzoate, p-aminosalicylate, clofibrate, halofenate, alpha-cyano-4-hydroxycinnamate and benfluorex. All of these drugs inhibit fatty acid biosynthesis by isolated rat liver cells, albeit with different effectiveness. In contrast, the cmpd have differential effects on fatty acid esterification and oxidation by isolated hepatocytes. An attempt is made to describe in molecular terms the underlying mechanisms of the acute inhibitory effects of the mono-aromatic derivatives on hepatic lipogenesis. It is proposed that all of the drugs exert an inhibitory action at the level of acetyl-CoA carboxylase, the enzyme generally considered to catalyze the rate-limiting step in hepatic fatty acid synthesis. This inhibitory effect may be either direct, i.e. by an alteration of the enzyme's structure as a results of interaction between drug and enzyme, or indirect, i.e. through a drug-induced change in the cellular levels of allosteric effectors of acetyl-CoA carboxylase. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| 水環境危害等級（WGK） | 2 |
| TSCA 収載状態 | TSCA listed |
| RTECS 番号 | VO1225000 |
| 輸送番号（UN） | UN 1789 8/PG 3 |
| 毒性 | LD50 orally in mice: 4 g/kg (Bavin) |
| 税関コード | 29225000 |
| 危険文句（R） | 22-36-36/37/38-45-35-61 |
| 化審法 | (3)-3039 |
| 危険表示 | Xn,Xi,T |
| 安全措置（S） | 26-37/39-45-53-36-36/37/39 |
| 貯蔵分類 | 11 - Combustible Solids |
| 有害物質データ | 65-49-6(Hazardous Substances Data) |
用途
解説
フクシンアルデヒド試薬(fuchsin-aldehyde reagent)ともいう．ドイツの有機化学者H. Schiffによって創案された．アルデヒドの検出試薬として有名であり，アルデヒドとケトンを判別する目的で用いられることが多い．フクシン0.2 g を水200 mL に溶解，これに亜硫酸15 mL を加えて一夜放置すると，脱色されて無色になる．この試薬1滴をアルデヒドの検液に加えて振ると，室温で反応して赤紫色を呈する．しかし，ケトンはこの反応がみられない．この反応はアルデヒドに対しては鋭敏な呈色反応である．森北出版「化学辞典（第2版）
用途
4-アミノサリチル酸（4-アミノサリチルさん）は、結核の治療に使われた抗生物質である。潰瘍性大腸炎やクローン病に強い効果があることが認められ、1940年代から炎症性腸疾患の治療に用いられている。 医薬品としてはカルシウム塩が用いられる。
用途
医薬原料。
使用
antimycobacterial antitubercular;NF-kB inhibitor.4-Aminosalicylic acid (p-aminosalicylic acid, PAS), an antituberculosis drug, is a model active pharmaceutical ingredient to study salt and cocrystal formation in a multiple hydrogen-bonding functionality molecule with carboxylic acid, amine, and phenol groups.It has also been used as a second line agent to sulfasalazine in people with inflammatory bowel disease such as ulcerative colitis and Crohn's disease.It is typically taken by mouth.
一般的な説明
4-Aminosalicylic acid occurs as a white to yellowish white crystalline solid that darkens on exposure to light or air. It is slightly soluble in water but more soluble in alcohol. Alkali metal salts and the nitric acid salt are soluble in water, but the salts of hydrochloric acid and sulfuric acid are not. The acid undergoes decarboxylation when heated. An aqueous solution has a pH of approximately 3.2. PAS is administered orally in the form of the sodium salt, usually in tablet or capsule form. Symptoms of gastrointestinal irritation are common with both the acid and the sodium salt. Various enteric-coated dosage forms have been used in an attempt to overcome this disadvantage. Other forms that are claimed to improve gastrointestinal tolerance include the calcium salt, the phenyl ester, and a combination with an anion exchange resin (Rezi-PAS). An antacid such as aluminum hydroxide is frequently prescribed. The oral absorption of PAS is rapid and nearly complete, and it is widely distributed into most of the body fluids and tissues, with the exception of the CSF, in which levels are significantly lower.It is excreted primarily in the urine as both unchanged drug and metabolites.
製法・合成法
純化方法
Crystallise the acid from EtOH. [Beilstein 14 IV 1967.]