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Hydroflumethiazide

HCID 3647
노트반응
기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
부분 구조 검색유사 구조 찾기

기본 정보

CAS
135-09-1
표준 SMILES
NS(=O)(=O)c1cc2c(cc1C(F)(F)F)NCNS2(=O)=O
InChIKey
DMDGGSIALPNSEE-UHFFFAOYSA-N
분자식
C8H8F3N3O4S2
평균 분자량
331.3 g/mol
단동위원소 질량
330.99083258

개요

Hydroflumethiazide is a benzothiadiazine consisting of a 3,4-dihydro-HH-1,2,4-benzothiadiazine bicyclic system dioxygenated on sulfur and carrying trifluoromethyl and aminosulfonyl groups at positions 6 and 7 respectively. A diuretic with actions and uses similar to those of hydrochlorothiazide. It has a role as a diuretic and an antihypertensive agent. It is a thiazide and a benzothiadiazine.

이름 및 식별자

우선 이름
Hydroflumethiazide
IUPAC
1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1λ6,2,4-benzothiadiazine-7-sulfonamide
영어명
Hydroflumethiazide
분자식
C8H8F3N3O4S2
분자량
331.29

이름 및 동의어

hydroflumethiazide135-09-1DiuredeminaDiucardinGlomerulinSaluronHidroflumetiazidHydroflumethizideDiurometonFlutizideHidroalogenSpandiuril
이름 더 보기
hydolRivernaclexAdemilrontylelodrinsisuril
BristabBristurinElodrineFinuretHydrenoxLeodrineOlmagranRodiuran

데이터베이스 식별자

CAS
135-09-1
PubChem CID
3647
DTXSID
DTXSID3023132
ChEMBL
CHEMBL1763
ChEBI
CHEBI:5784
UNII
501CFL162R
EC Number
205-173-8

물성

구조 계산 물성

XLogP
0.4
극성 표면적
135 Ų
수소 결합 공여자 수
3
수소 결합 수용자 수
10
회전 가능 결합 수
1
무거운 원자 수
20
형식 전하
0
복잡도
578

실험 및 물리화학적 성질

Drugs · 2건

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Cardiovascular system -> Diuretics

pH1 IN 100 DISPERSION IN WATER: BETWEEN 4.5-7.5
LogP · 3건

log Kow = 0.36

-0.2

0.36

OdorODORLESS
Color/Form · 2건

CRYSTALS

White to cream colored, finely divided, crystalline powder

Solubility · 5건

Solubility (mg/ml) at 25 °C: acetone >100; methanol 58; acetonitrile 43; water 0.3; ether 0.2; benzene <0.1.

INSOL IN ACID

Soluble in dilute alkali but unstable in alkaline solutions.

SOL IN ALC; FREELY SOL IN ACETONE

8.58e-01 g/L

Human Drugs · 4건

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Thiazide Diuretics

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

Melting Point · 3건

272-273

272-273 °C

272 - 273 °C

안전 및 규제

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

GHS 분류

GHS Classification · 4건

Danger

H317 (97.6%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

유해성 정보

Regulatory Information2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-(trifluoromethyl)-, 1,1-dioxide: Does not have an individual approval but may be used under an appropriate group standard
Other Safety InformationIMAP assessments - 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-(trifluoromethyl)-, 1,1-dioxide: Human health tier I assessment
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).

Hazard Classes and CategoriesSkin Sens. 1 (97.6%)

안전 및 보호

Storage ConditionsCommercially available hydroflumethiazide tablets should be stored at room temperature (approximately 25 °C) ... .
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.

화학 및 산업

약리 정보

ATC Code · 2건

C - Cardiovascular system

QC - Cardiovascular system

Protein Binding74%
Pharmacodynamics · 1건

Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Mechanism of Action · 6건

Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

...BENZOTHIADIAZIDES HAVE DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE...INDEPENDENT OF ANY EFFECT ON CARBONIC ANHYDRASE. /THIAZIDE DIURETICS/

관련 반응

0건
반응 기록 만들기

현재 필터 조건에 해당하는 반응 기록이 없습니다.

화합물 노트

불러오는 중…

이 페이지에서기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
Physical Description
Solid
Stability/Shelf LifeUNSTABLE IN ALKALINE SOLN
Dissociation Constants · 2건

8.9

PK1 8.9; PK2 10.7

Other Experimental PropertiesFORMS WATER-SOL SALTS WITH BASES

물리화학적 성질

녹는점
272 · 272-273
끓는 점
531.6 · 531.6±60.0 °C(Predicted)
밀도
1.5955 · 1.5955 (estimate)
저장 조건
2 · Keep in dark place,Sealed in dry,2-8°C
용해도
DMSO(약간 용해됨), 메탄올(약간 용해됨)
물리적 상태
고체
산도 계수 (pKa)
8.9 · 8.9, 8.2(at 25℃)
색상
하얀색
수용성
329.9 mg/L · 329.9mg/L(상온)
주요 응용
제약소분자 약용
InChI
1S/C8H8F3N3O4S2/c9-8(10,11)4-1-5-7(2-6(4)19(12,15)16)20(17,18)14-3-13-5/h1-2,13-14H,3H2,(H2,12,15,16)
InChIKey
DMDGGSIALPNSEE-UHFFFAOYSA-N
SMILES
O=S1(C2=CC(S(=O)(N)=O)=C(C(F)(F)F)C=C2NCN1)=O
EPA
2 H-1,2,4-Benzothiadiazine-7-sulfonamide, · 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-6-(trifluoromethyl)-, 1,1-dioxide (135-09-1)

화학적 성질

White Solid

독성 정보

Interactions · 5건

...DISRUPTION OF URICOSURIC THERAPY BY ADMIN OF DIURETIC WHICH INCR PLASMA URIC ACID LEVELS (THIAZIDES)... /THIAZIDE DIURETICS/

CONCURRENT ADMIN OF THIAZIDE DIURETICS & MONOAMINE OXIDASE INHIBITORS MAY INCR HYPOTENSION. /THIAZIDE DIURETICS/

ELECTROLYTE DISTURBANCES PRODUCED BY /HYDROFLUMETHIAZIDE/ PREDISPOSE PATIENT TO...TOXICITY /OF DIGITALIS GLYCOSIDES/. SEVERE POTASSIUM DEPLETION MAY OCCUR /WITH CONCOMITANT CORTICOSTEROIDS, CORTICOTROPIN & AMPHOTERICIN B/. MAY ANTAGONIZE EFFECTS OF ORAL ANTICOAGULANTS.

/HYDROFLUMETHIAZIDE MAY PROLONG/ NEUROMUSCULAR BLOCKADE /OF/ NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS...TUBOCURARINE CHLORIDE OR GALLAMINE TRIETHIODIDE...RENAL CLEARANCE OF LITHIUM...DECREASED...SERUM LITHIUM /MAY INCREASE IN PATIENTS RECEIVING LITHIUM CARBONATE & LONG-TERM DIURETIC/.

For more Interactions (Complete) data for HYDROFLUMETHIAZIDE (22 total), please visit the HSDB record page.

Human Toxicity Excerpts · 2건

In addition to diuresis and resultant dehydration, overdosage of thiazides may produce lethargy, nausea, weakness, and electrolyte imbalance; lethargy may progress to coma within a few hours with minimal depression of respiratory and cardiovascular function and without evidence of dehydration or serum electryolye change. The mechanism of thiazide-induced CNS depression is unknown. GI irritation and hypermotility may occur, and temporary elevation of the BUN has been reported. Serum electrolyte changes (e.g., hypokalemia, hypochloremia, hyponatremia) may occur, especially in patients with impaired renal function. /Thiazides/

May suppress lactation, but compatible /SRP: with breast feeding/. /Thiazide diuretics, from table/

Drug Induced Liver Injury · 6건

Drug Induced Liver Injury Rank (DILIrank 2.0)

Hydroflumethiazide

Ambiguous-DILI-concern

2

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Antidote and Emergency TreatmentThiazide diuretic overdose should be treated by immediate evacuation of the stomach followed by supportive symptomatic treatment and monitoring of serum electrolyte concentrations and renal function. /Thiazide diuretic/
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

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
rtecs
DK9625000
독성
LD50 in mice (mg/kg): >8000 orally, 750 i.v., 6280 i.p. (Piala)
HS 번호
2935904000
risk_code
42/43
hazard_code
Xn,Xi
safety_code
36
위험 참고 사항
Irritant
Hazard Classifications
Resp. Sens. 1Skin Sens. 1
스토리지 클래스
11 - Combustible Solids
유해 물질 데이터
135-09-1(Hazardous Substances Data)

NATURE OF CHEM INTERACTION BETWEEN THIAZIDES & SPECIFIC RENAL RECEPTORS RESPONSIBLE FOR CHLORURETIC EFFECT IS NOT KNOWN; NO CRITICAL ENZYMATIC REACTIONS HAVE BEEN IDENTIFIED. /THIAZIDES/

THIAZIDES INHIBIT REABSORPTION OF SODIUM &...CHLORIDE IN DISTAL SEGMENT. ... AS CLASS...HAVE IMPORTANT ACTION ON EXCRETION OF POTASSIUM THAT RESULTS FROM INCR SECRETION OF CATION BY DISTAL TUBULE. ... GLOMERULAR FILTRATION RATE MAY BE REDUCED BY THIAZIDES, PARTICULARLY WITH IV ADMIN FOR EXPTL PURPOSES. /THIAZIDES/

THIAZIDES MAY DECR EXCRETION OF URIC ACID IN MAN, THUS INCR ITS CONCN IN PLASMA. HYPERURICEMIC EFFECT RESULTS PRIMARILY FROM INHIBITION OF TUBULAR SECRETION OF URATE. ... UNLIKE MOST OTHER NATRIURETIC AGENTS...DECR RENAL EXCRETION OF CALCIUM RELATIVE TO THAT OF SODIUM... /ENHANCE/ EXCRETION OF MAGNESIUM... /THIAZIDES/

For more Mechanism of Action (Complete) data for HYDROFLUMETHIAZIDE (11 total), please visit the HSDB record page.

Biological Half-Life · 3건

It appears to have a biphasic biological half-life with an estimated alpha-phase of about 2 hours and an estimated beta-phase of about 17 hours

Half-life is 12-27 hr. /From table/

/Hydroflumethiazide has a/ estimated distribution half-life of approximately 2 hours and an estimated terminal elimination half-life of approximately 17 hours ... .

Metabolism/Metabolites · 2건

Essentially unchanged

AFTER REPEATED ORAL ADMIN OF 100 MG EVERY 24 HR FOR 7 DAYS TO HEALTHY MALES, METABOLITE 2,4-DISULFAMYL-5-TRIFLUOROMETHYLANILINE DETERMINED.

FDA Pharmacological Classification · 6건

501CFL162R

HYDROFLUMETHIAZIDE

Physiologic Effects [PE] - Increased Diuresis

Established Pharmacologic Class [EPC] - Thiazide Diuretic

Chemical Structure [CS] - Thiazides

Hydroflumethiazide is a Thiazide Diuretic. The physiologic effect of hydroflumethiazide is by means of Increased Diuresis.

MeSH Pharmacological Classification · 3건

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Agents that promote the excretion of urine through their effects on kidney function.

Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.

Absorption, Distribution and Excretion · 6건

Hydroflumethiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract

THIAZIDES ARE ABSORBED FROM GI TRACT & OWE THEIR USEFULNESS LARGELY TO THEIR EFFECTIVENESS BY ORAL ROUTE. ABSORPTION IS RELATIVELY RAPID. MOST AGENTS SHOW DEMONSTRABLE DIURETIC EFFECT WITHIN HR AFTER ORAL ADMIN. /THIAZIDE DIURETICS/

IN GENERAL, THIAZIDES WITH RELATIVELY LONG DURATIONS OF ACTION SHOW PROPORTIONATELY HIGH DEGREE OF BINDING TO PLASMA PROTEINS & ARE REABSORBED BY RENAL TUBULES. ... DRUG PASSES READILY THROUGH PLACENTAL BARRIER TO FETUS. ALL THIAZIDES PROBABLY UNDERGO ACTIVE SECRETION IN PROXIMAL TUBULE. /THIAZIDE DIURETICS/

AFTER IV INFUSION OF HYDROFLUMETHIAZIDE, 2 DISTRIBUTION PHASES, T/2 OF 0.26 & 0.85 HR. AFTER SINGLE ORAL DOSE OF 2 UMOL/KG, T/2 BETA SHORTER THAN AFTER DOSE OF 6 UMOL/KG, WITH MEAN T/2 BETA OF 8.7 & 17.9 HR.

AFTER ORAL ADMIN OF HYDROFLUMETHIAZIDE EVERY 24 HR FOR 7 DAYS, MEAN BIOL T/2 OF 6.85 HR; MEAN T/2 OF METABOLITE WAS 17.7 HR. 0.652 OF DOSE EXCRETED UNCHANGED IN URINE, 0.049 AS METABOLITE. MEAN RENAL PLASMA CLEARANCE OF DRUG WAS 0.356 L/HR/KG.

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

Cellular LocationsCytoplasm
Metabolite PathwaysHydroflumethiazide Action Pathway

용도 및 제조

UsesTHERAP CAT: Antihypertensive; diuretic.
Methods of Manufacturing · 2건

HOLDREDGE ET AL, J AM CHEM SOC 81, 4807 (1959); CLOSE ET AL, J AM CHEM SOC 82, 1132 (1960); YALE ET AL J AM CHEM SOC 2042; NOVELLO ET AL, J ORG CHEM 25, 970 (1960). NUMEROUS PATENTS, EG, LUND ET AL, US PATENT 3,254,076 (1966 TO LOVENS).

m-Aminobenzotrifluoride + chlorosulfonic acid + ammonia + formaldehyde (chlorosulfonation/sulfonamide formation/carbonyl condensation).

Formulations/Preparations · 2건

MARKET PREPN (TABLETS) 50 MG.

Grade: National Formulary grade of chemical.

Use ClassificationPharmaceuticals
General Manufacturing InformationSOLUBILITY VALUES OF HYDROFLUMETHIAZIDE INCR BY RAISING TEMP IN PRESENCE OF VARIOUS TWEENS.

응용 분야

용도Labelled Hydroflumethiazide. Antihypertensive; diuretic.

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