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4-아미노살리실 산

4-Aminosalicylic Acid

HCID 4649
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기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
부분 구조 검색유사 구조 찾기

기본 정보

CAS
65-49-6
표준 SMILES
Nc1ccc(C(=O)O)c(O)c1
InChIKey
WUBBRNOQWQTFEX-UHFFFAOYSA-N
분자식
C7H7NO3
평균 분자량
153.14 g/mol
단동위원소 질량
153.04259309

개요

4-aminosalicylic acid is an aminobenzoic acid that is salicylic acid substituted by an amino group at position 4. It has a role as an antitubercular agent. It is an aminobenzoic acid and a member of phenols. It is functionally related to a salicylic acid. It is a conjugate acid of a 4-aminosalicylate(1-).

이름 및 식별자

우선 이름
4-Aminosalicylic Acid
IUPAC
4-amino-2-hydroxybenzoic acid
현지명
4-아미노살리실 산
영어명
4-Aminosalicylic acid
분자식
C7H7NO3
분자량
153.14

이름 및 동의어

4-Aminosalicylic acid4-Amino-2-hydroxybenzoic acid65-49-6Aminosalicylic acidP-AMINOSALICYLIC ACIDParamycinParasalPaserParasalindonDeapasilApacilGabbropas
이름 더 보기
4-아미노살리실산4-아미노살리실산4-아미노살리실릭애씨드4-아미노살리실릭애씨드및그염류PASPasa4-AsaSCHIFF REAGENTSCHIFF'S REAGENTApas
ParasalicilAminoparEntepasPamacylPasalonPasnodiaPasolacPropasa

데이터베이스 식별자

CAS
65-49-6
PubChem CID
4649
DTXSID
DTXSID2022591
ChEMBL
CHEMBL1169
ChEBI
CHEBI:27565
UNII
5B2658E0N2
EC Number
200-613-5
Nikkaji
J4.838K

물성

구조 계산 물성보충 중

XLogP
1.3
극성 표면적
83.6 Ų
수소 결합 공여자 수
3
수소 결합 수용자 수
4
회전 가능 결합 수
1
무거운 원자 수
11
형식 전하
0
복잡도
160

실험 및 물리화학적 성질

Chemical ClassesNitrogen Compounds -> Aminobenzoic Acids
Drugs · 2건

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics

pHPH (SATURATED AQ SOLN): BETWEEN 3 & 3.7
SpringerMaterials PropertiesDiamagnetic susceptibility
LogP · 3건

LogP= 1.32

1.6

0.87

OdorODORLESS, OR HAS SLIGHT ACETOUS ODOR
Color/Form · 4건

MINUTE CRYSTALS FROM ALC

WHITE, OR NEARLY WHITE, BULKY POWDER

NEEDLES, PLATES FROM ALC-ETHER

A reddish-brown crystalline powder is obtained on recrystallization from ethanol-ether.

Solubility · 5건

1 G SOL IN ABOUT 7 ML WATER; SLIGHTLY SOL IN ALC /CALCIUM SALT/

PH OF 1% SOLN: ABOUT 7; FREELY 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 HYDROXIDE

Virtually insoluble in benzene, choroform, or carbon tetrachloride

안전 및 규제

안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.

GHS 분류

GHS Classification · 4건

Warning

H315 (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.

유해성 정보

Regulatory Information · 2건

REACH registered substance: 4-aminosalicylic acid (EC: 200-613-5)

Benzoic acid, 4-amino-2-hydroxy-: Does not have an individual approval but may be used under an appropriate group standard

Other Safety InformationIMAP assessments - Benzoic acid, 4-amino-2-hydroxy-: Environment tier I assessment
Hazards SummaryNot expected to increase congenital malformations based on animal studies; [REPROTOX] Oral LD50 (mouse) = 4000 mg/kg; [RTECS] An eye irritant; Targets the GI system and liver; [MSDSonline] See p-Aminosalicylic acid sodium salt dihydrate.
FDA Requirements · 1건

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 amended; 21 U.S.C. 321-392).

Special Reports · 2건

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 G; Drugs 37 (Jan): 73-86 (1989)]

화학 및 산업

약리 정보

ATC Code · 2건

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Protein Binding50-60%
Pharmacodynamics · 1건

Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against <i>Mycobacterium tuberculosis</i> (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.

Mechanism of Action · 3건

There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against <i>Mycobacterium tuberculosis</i>. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by <i>M. tuberculosis</i>.

The antimicrobial activity of aminosalicylic acid is highly specific, and microorganisms other than Mycobacterium tuberculosis are unaffected. Most nontuberculous mycobacteria are not inhibited by the drug.

Aminosalicyclic acid is a structural analog of paraaminobenzoic acid, and its mechanism of action appears to be very similar to that of the sulfonamides. Since the sulfonamides are ineffective against Mycobacterium tuberculosis, and aminosalicyclic is inactive against sulfonamide susceptible bacteria, it is probable that the enzymes responsible for folate biosynthesis in various microorganisms may be quite exacting in their capacity to distinguish various analogs from the true metabolite.

관련 반응

96건
반응 기록 만들기
HRID 18440 반응식
HRID 18440반응물로uspto-grants-2010_06
HRID 71535 반응식
HRID 71535반응물로uspto-grants-2014_09
HRID 76646 반응식
HRID 76646반응물로uspto-grants-2014_09
HRID 98090 반응식
HRID 98090반응물로Training data from https://doi.org/10.1039/C8SC04228D (2/10)
HRID 101517 반응식
HRID 101517반응물로Training data from https://doi.org/10.1039/C8SC04228D (2/10)
HRID 107654 반응식
HRID 107654반응물로Training data from https://doi.org/10.1039/C8SC04228D (2/10)
HRID 136213 반응식
HRID 136213생성물로Training data from https://doi.org/10.1039/C8SC04228D (9/10)
HRID 162068 반응식
HRID 162068반응물로Training data from https://doi.org/10.1039/C8SC04228D (9/10)
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화합물 노트

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Human Drugs · 3건

Breast Feeding; Lactation; Milk, Human; Anti-infective Agents; Antitubercular Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Melting Point · 3건

150-151 °C, with effervescence

NEEDLES FROM ALC; MP: 115 °C /ETHYL ESTER/

150.5 °C

Vapor Pressure0.000004 [mmHg]
Physical Description · 2건

White or nearly white solid; Affected by light and air; [Hawley] Beige powder; [MSDSonline]

Solid

물리화학적 성질

녹는점
135 · 135-145 °C (lit.)
끓는 점
276.03 °C · 276.03°C (rough estimate)
밀도
1.3585 · 1.3585 (rough estimate)
굴절률
1.55 · 1.5500 (estimate)
저장 조건
Keep in dark place,Inert atmosphere,Room temperature
용해도
1.69 g/L · 1.69g/L
물리적 상태
가루
산도 계수 (pKa)
3.25 · 3.25(at 25℃)
색상
무색의
수소이온지수(pH)
3.5 · 3.5 (1g/l, H2O, 20℃)
수용성
2 g/L · 2g/L(20℃)
Merck
14 · 14,477
BRN
473071 · 473071
Specific Activity
17.6 · 17.6-26.4nmol/min·mg
BCS Class
4 · 4/2
안정성
흡습성
주요 응용
펩타이드 합성
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
NIST
Aminosalicylic acid(65-49-6)
EPA
4 · 4-Aminosalicylic acid (65-49-6)

화학적 성질

beige powder

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 SV; Drug Therapy 15 (Nov): 91-92, 97-100 (1985)]

Hazard Classes and CategoriesSkin Irrit. 2 (43.5%)

안전 및 보호

Storage ConditionsStore below 90 °C (104 °F), unless otherwise specified by manufacturer. Store in tight, light resistant containers.
Disposal Methods · 1건

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.

독성 정보

Interactions · 5건

...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.

Adverse EffectsOccupational 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 · 3건

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 · 6건

Drug Induced Liver Injury Rank (DILIrank 2.0)

Aminosalicylic acid

vMOST-DILI-concern

5

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

Non-Human Toxicity Excerpts · 2건

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
EPA Human Health Benchmarks for Pharmaceuticals · 6건

Aminosalicylic acid

279.7

1183.4

The adult dosage of four grams (one packet) three times per day should be given by sprinkling on apple sauce or yogurt or by swirling in the glass to suspend the granules in an acidic drink such as tomato or orange juice.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 12000 mg/day, Lowest Therapeutic Dose (LTD): 150.0 mg/kg-day, and Screening Dose: 0.1 mg/kg-day.

1-Jun-10

규제 정보

FDA Requirements · 1건

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 amended; 21 U.S.C. 321-392).

안전 데이터

wgk
2
tsca
TSCA listed
rtecs
VO1225000
ridadr
UN 1789 8/PG 3
독성
LD50 orally in mice: 4 g/kg (Bavin)
HS 번호
29225000
risk_code
22-36-36/37/38-45-35-61
hazard_code
Xn,Xi,T
safety_code
26-37/39-45-53-36-36/37/39
기존화학 물질
KE-01389
스토리지 클래스
11 - Combustible Solids
유해 물질 데이터
65-49-6(Hazardous Substances Data)
Biological Half-Life
The drug has a half life of about 1 hour, and concentrations in plasma are negligible within 4 to 5 hours after a single conventional dose.
Metabolism/Metabolites · 6건

Hepatic.

ACETYLATION IS MAJOR ROUTE FOR INACTIVATION OF MANY DRUGS SUCH AS ... P-AMINOSALICYLIC ACID... ENZYMES WHICH CATALYSE THESE REACTIONS, ACETYL COENZYME A:N-ACETYLTRANSFERASES (EC2.3.1.5), ARE LOCATED IN LIVER CYTOSOL.

WHEN ADMIN ORALLY TO MAN IT IS RAPIDLY ABSORBED, & IS EXCRETED IN URINE AS UNCHANGED P-AMINOSALICYLIC ACID & AS ACETYL GLUCURONYL, GLYCYL & GLUTAMINYL CONJUGATES.

YIELDS 5-AMINO-2-CARBOXYPHENYL-BETA-D-GLUCURONIDE IN MAN. 4-AMINOCATECHOL IN PSEUDOMONAS. 4-AMINOSALICYLOYLGLUTAMINE & 4-AMINOSALICYLOYLGLYCINE IN MAN. /TABLE/

Blood from tuberculosis patients was cultured before, during, and after withdrawal of therapy involving five different drug combinations if isoniazid, thiacetazone, p-aminosalicyclic acid, and streptomycin. The approaches used to detect DNA damage were chromosome aberrations and sister chromatid exchanges (SCEs). A total of 179 subjects were analyzed. In combo these drugs showed synergistic, additive, and antagonistic effects, though they were found to be nonclastogenic individually. Four of the drug combinations, isoniazid plus thiacetazone, isoniazid plus p-aminosalicyclic acid, isoniazid plus thiacetazone plus streptomycin, and isoniazid plus p-aminosalicyclic acid plus streptomycin, induced a significant incr in the frequency of aberrations, whereas isoniazid plus streptomycin did not induce aberrations. In fact, streptomycin appeared to reduce the frequency of aberrations. SCEs were incr in only two patients: one treated with isoniazid plus thiacetazone and the other with isoniazid plus p-aminosalicyclic acid. The frequency of aberrations after withdrawal of therapy was decr; it was slightly higher than the controls, though it was insignificant. The return to normalcy could be due to elimination of damaged cells or the repair of DNA in lymphocytes. Though the drug-induced aberrations do not persist after withdrawal of therapy, the chromosome damaging combo of drugs should be used with caution, because the possibility of meiotic chromosome damage in germ cells (during therapy), which might be passed on to the next generation, cannot be ruled out.

For more Metabolism/Metabolites (Complete) data for P-AMINOSALICYLIC ACID (9 total), please visit the HSDB record page.

MeSH Pharmacological Classification · 1건

Drugs used in the treatment of tuberculosis. They are divided into two main classes: first-line agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and second-line drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.

Absorption, Distribution and Excretion · 5건

BIOAVAILABILITY STUDIES ON P-AMINOSALICYLIC ACID & ITS SALTS IN 12 SUBJECTS. COLORIMETRIC ASSAY INDICATED THAT PEAK BLOOD LEVELS OCCURRED @ 0.5, 0.75, 1.5, & 3 HR FOR SODIUM, POTASSIUM, & CALCIUM SALTS & P-AMINOSALICYLIC ACID, RESPECTIVELY.

URINE EXCRETION DATA SHOWED ABSORPTION TO BE ESSENTIALLY COMPLETE ALTHOUGH RATES OF ABSORPTION DIFFERED.

Aminosalicyclic acid is readily absorbed from the gastrointestinal tract. A single oral dose of 4 g of the free acid produces maximal concentrations in plasma of about 75 ug/ml within 1.5 to 2 hours. The sodium salt is absorbed even more rapidly. The drug appears to be distributed throughout the total body water and reaches high concentrations in pleural fluid and caseous tissue. However, values in CSF are low, perhaps because of active outward transport.

Over 80% of the drug is excreted in the urine; more than 50% is in the form of the acetylated compound. The largest portion of the remainder is made up of the free acid.

For more Absorption, Distribution and Excretion (Complete) data for P-AMINOSALICYLIC ACID (8 total), please visit the HSDB record page.

Cellular LocationsCytoplasm

용도 및 제조

Uses · 5건

Used as an industrial preservative, a chemical intermediate, and an antitubercular drug; [HSDB]

Industrial preservative.

Used as a chemical intermediate for the synthesis of bromopride; metoclopramide; xipamide

MEDICATION (VET)

MEDICATION

Methods of Manufacturing · 2건

PREPD BY HEATING M-AMINOPHENOL WITH AMMONIUM CARBONATE OR POTASSIUM BISCARBONATE IN SOLN UNDER PRESSURE. PREPN FROM SODIUM P-AMINOSALICYLATE.

Derivation: From m-aminophenol and potassium bicarbonate, soluble under pressure.

Formulations/Preparations · 2건

USP

Available commercially as the free acid and as the sodium dihydrate salt.

General Manufacturing InformationBenzoic acid, 4-amino-2-hydroxy-: ACTIVE
응용 분야 · 2건

용도antimycobacterial 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.

일반 설명4-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.

상·하류 제품 정보

상류 원료

2,4-디니트로페닐아세틱 산1-Butyl nitrite황화나트륨아황산나트륨2-히드록시-4-니트로벤조산이산화탄소Potassium hydroxide solution메틸산 나트륨메틸2,4-디니트로페닐아세테이트질산Esterified product3-아미노페놀2-히드록시벤조니트릴페닐초산암모늄 카보네이트P-아미노살리실산나트륨염

하류 제품

4-Chlorosalicylic acidMethyl 4-acetamido-2-methoxybenzoateoptical plastics based on coplymer of diene macromolecule메틸4-아세트아미도-2-메톡시벤조에이트2-hydroxy-4-(4-pyridyl)benzoic acid페닐-4-아미노살리실레이트

추가 설명

정의ChEBI: An aminobenzoic acid that is salicylic acid substituted by an amino group at position 4.