氯噻酮 | 77-36-1

• 物质功能分类: 原料药 - 泌尿系统用药 - 利尿药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 氯噻酮
• 中文别名: 氯塞酮；2-氯-5-(2,3-二氢-1-羟基-3-氧代-1H-异吲哚-1-基)苯磺酰胺
• 英文名称: chlorthalidon
• 英文别名: 2-chloro-5-(1-hydroxy-3-oxo-isoindolin-1-yl)-benzenesulfonic acid amide；chlorthalidone；2-chloro-5-(1-hydroxy-3-oxo-2H-isoindol-1-yl)benzenesulfonamide
• CAS: 77-36-1
• 化学式: C₁₄H₁₁ClN₂O₄S
• mdl: MFCD00036257
• 分子量: 338.771
• InChiKey: JIVPVXMEBJLZRO-UHFFFAOYSA-N

物化性质

• 熔点：
  265-267°C (dec.)
• 密度：
  1.3356 (rough estimate)
• 溶解度：
  DMSO：可溶5mg/mL，澄清（加热）
• 物理描述：
  Solid
• 颜色/状态：
  Crystals from 50% acetic acid
• 碰撞截面：
  166.7 Ų [M+H-H2O]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

肝脏

Liver

来源:DrugBank

毒理性

• 毒性总结

识别：氯噻酮是一种噻嗪类利尿剂。氯噻酮用于治疗高血压，可以作为单一治疗药物或与其他抗高血压药物联合使用。氯噻酮还用作心力衰竭、肝硬化和皮质类固醇及雌激素治疗相关水肿的辅助治疗。氯噻酮还发现对各种形式的肾功能不全所致的水肿有用，例如肾病综合征。如果存在液体潴留的证据，氯噻酮也用于治疗经前紧张。氯噻酮在尿崩症患者中具有矛盾的抗利尿作用。人体暴露：主要风险和靶器官：氯噻酮在治疗使用中通常耐受性良好。临床毒性相对罕见，可能由过量、不良反应或过敏反应引起。急性毒性：主要风险包括：低钾血症、低钠血症、低血压、心脏心律失常和中央神经系统效应。靶器官：肾脏、心脏、中枢神经系统。慢性毒性和不良反应包括：代谢紊乱、过敏反应、加重肾脏和/或肝脏功能不全、胃肠紊乱、血液病和中央神经系统效应。临床效应总结：急性毒性：症状可能包括：低钾血症、低钠血症、脱水、低血容量、心脏心律失常（由于低钾血症导致的室性期外收缩和尖端扭转型室速）、头晕、乏力、感觉异常。慢性毒性和不良反应：报告了多种紊乱：代谢：低钾血症、低钠血症、高血糖、高尿酸血症、代谢性碱中毒、加重肾功能不全。心血管：心脏心律失常、增强洋地黄对心肌的作用、直立性低血压。中枢神经系统：头晕、眩晕、感觉异常、头痛、黄视。胃肠道：厌食、胃部刺激、恶心、呕吐、痉挛、腹泻、便秘、由于肝内胆汁淤积引起的黄疸、胰腺炎、唾液腺炎、口干、肝功能不全、肠道溃疡。过敏反应：紫癜、血管内免疫性溶血、肺炎、皮肤皮疹、荨麻疹、湿疹、扁平苔藓样反应；光敏性，类似于亚急性皮肤红斑狼疮；血管炎；史蒂文斯-约翰逊综合症。血液学：血小板减少症、粒细胞减少症、白细胞减少症、再生障碍性贫血和溶血性贫血。呼吸道：急性非心源性肺水肿。其他：痛风发作、增加血浆胆固醇和甘油三酯浓度。用途：氯噻酮可能预防患有高钙尿症的患者的肾结石形成。氯噻酮可能改善与梅尼埃病相关的眩晕。禁忌症：无尿、对磺酰胺衍生物药物过敏、肝性脑病。注意事项：在以下情况下应谨慎使用氯噻酮：肝功能受损，因为它可能增加肝性脑病的风险。肾功能障碍可能会发生，因为它可能会进一步降低肾功能并诱发氮质血症。累积效应可能会在肾功能受损的患者中发展。接受奎尼丁样抗心律失常药、胺碘酮、索他洛尔治疗的患者。避免在痛风患者中使用，因为它可能诱发疾病的发作。应仔细观察患者是否有液体和电解质失衡的迹象。氯噻酮可能通过降低血清钾浓度增强洋地黄糖苷的毒性。有报道称可能会加剧或诱发系统性红斑狼疮。氯噻酮穿过胎盘，有报道称母亲治疗后出现了新生儿黄疸、血小板减少和电解质失衡。氯噻酮会排入母乳中。治疗可能会抑制泌乳。在存在以下医学问题时应谨慎使用氯噻酮：糖尿病、高钙血症、高尿酸血症、狼疮病史、胰腺炎、交感神经切除术。进入途径：口服途径是最常见的给药途径。可能会意外或故意摄入大剂量。动力学：吸收途径：氯噻酮从胃肠道不规则吸收。口服给药的生物利用度约为65%。约75%与血浆蛋白结合，血液与血浆的比例为72.5%。氯噻酮穿过胎盘。生物学半衰期：血浆半衰期约为44±10小时，并随年龄增长而增加。终末半衰期为35至54小时。这可能是由于氯噻酮与红细胞的强烈结合。代谢：氯噻酮可能发生代谢，但代谢物尚未被识别。消除途径：在长期给药期间，有报道称30至60%以原形从尿液中排出。氯噻酮排入母乳中。它的乳：血浆比例非常低。氯噻酮是一种具有长效和低毒性的口服利尿剂。大多数有毒效应是由于电解质失衡，包括低氯性碱中毒、低钠血症、低钾血症和低镁血症。高钙血症和低磷血症的机制尚不清楚。噻嗪类药物会增加血浆中的胆固醇和甘油三酯浓度。氯噻酮还可能引起过敏反应。药效学：药物的利尿作用在口服剂量后两小时内发生，并持续长达72小时。它产生大量的电解质丢失，因此也失去水分。作用部位是

IDENTIFICATION: Chlorthalidone is a thiazide diuretic. Chlorthalidone is indicated in the management of hypertension as sole therapeutic agent or in combination with other antihypertensive drugs. Chlorthalidone is used as adjunctive therapy in the treatment of edema associated with heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Chlorthalidone has also been found useful in the edema due to various forms of renal dysfunction such as nephrotic syndrome. Chlorthalidone has been used in the treatment of premenstrual tension if there is evidence of fluid retention. Chlorthalidone has a paradoxical antidiuretic effect in patients with diabetes insipidus. HUMAN EXPOSURE: Main risks and target organs: Chlorthalidone is generally well tolerated during therapeutic use. Clinical toxicity is relatively infrequent and may result from overdosage, adverse reactions or hypersensitivity. Acute toxicity: Main risks include: hypokalemia, hyponatremia, hypotension, cardiac arrhythmias and central nervous system effects. Target organs: kidney, heart, CNS. Chronic toxicity and adverse reactions include: Metabolic disturbances, hypersensitivity reactions, aggravation of renal and/or hepatic insufficiency, gastrointestinal disturbances, blood dyscrasias, and central nervous system effects. Summary of clinical effects: Acute toxicity: Symptoms may include: hypokalemia, hyponatremia, dehydration, hypovolemic, cardiac dysrhythmias (ventricular extrasystoles and torsade de pointes due to hypokalemia), dizziness, lethargy, paresthesias. Chronic toxicity and adverse reactions: Several disturbances have been reported: Metabolic: hypokalemia, hyponatremia, hyperglycemia, hyperuricemia, metabolic alkalosis, aggravation of renal insufficiency. Cardiovascular: cardiac arrhythmias, enhancing the effect of digitalis on cardiac muscle, orthostatic hypotension. Central Nervous System: dizziness, vertigo, paresthesias, headache, xanthopsia. Gastrointestinal: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice due to intrahepatic cholestasis, pancreatitis, sialoadenitis, dry mouth, hepatic insufficiency, intestinal ulceration. Hypersensitivity: purpura, intravascular immune hemolysis, pneumonitis, skin rashes, urticaria, eczema, lichen planus like reactions; photosensitivity, similar to subacute cutaneous lupus erythematosus; vasculitis; Stevens Johnson Syndrome. Hematological: thrombocytopenia, granulocytopenia, leucopenia, aplastic anemia, and hemolytic anemia. Respiratory tract: acute noncardiogenic pulmonary edema. Others: attacks of gout, increasing in plasma concentrations of cholesterol and triglycerides. Use: Chlorthalidone may prevent renal calculus formation in patients with hypercalciuria. Chlorthalidone may improve vertigo associated with Ménière disease. Contraindications: Anuria, hypersensitivity to sulfonamide-derived drugs, hepatic encephalopathy. Precautions: Chlorthalidone should be used with caution in: impaired hepatic function since it may increase the risk of hepatic encephalopathy. Renal impairment can occur since it can further reduce renal function, and precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function. Patients treated with quinidine-like anti-arrhythmics, amiodarone, sotalol. Avoid use in patients with gout since it can precipitate attacks of the disease. Patients should be carefully observed for signs of fluids and electrolyte imbalance. Chlorthalidone may enhance the toxicity of digitalis glycosides by depleting serum potassium concentrations. The possibility of exacerbation or precipitation of systemic lupus erythematosus has been reported. Chlorthalidone crosses the placenta and there have been reports of neonatal jaundice, thrombocytopenia, and electrolytes imbalances following maternal treatment. Chlorthalidone is excreted in breast milk. Treatment can inhibit lactation. Chlorthalidone should be used with caution when the following medical problems exist: diabetes mellitus, hypercalcemia, hyperuricemia, history of lupus erythematosus, pancreatitis, sympathectomy. Routes of entry: The oral route is the commonest route of administration. Accidental or deliberate ingestion of large doses may occur. Kinetics: Absorption by route of exposure: Chlorthalidone is erratically absorbed from the gastrointestinal tract. Bioavailability after oral administration is approximately 65%. About 75% is bound to plasma protein and the blood-to-plasma ratio is 72.5%. Chlorthalidone crosses the placenta. Biological half-life by route of exposure: The plasma half-life is about 44 +/- 10 hours and increases with age. The terminal half-life is 35 to 54 hours. This may be due to the strong binding of chlorthalidone to red blood cells. Metabolism: Chlorthalidone probably undergoes metabolism but the metabolites have not been identified. Elimination by route of exposure: During long-term administration, 30 to 60% has been reported to be excreted unchanged in the urine. Chlorthalidone is excreted in breast milk. It has a very low milk:plasma ratio. Chlorthalidone is an oral diuretic with prolonged action and low toxicity. Most of the toxic effects are due to electrolyte imbalance including hypochloremic alkalosis, hyponatremia, hypokalemia, and hypomagnesemia. The mechanism of hypercalcemia and hypophosphatemia are unknown. Thiazides increase the concentration of cholesterol and triglycerides in plasma. Chlorthalidone may also cause hypersensitivity reactions. Pharmacodynamics: The diuretic effect of the drug occurs within two hours after an oral dose and continues for up to 72 hours. It produces copious loss of electrolytes, and consequently, of water. The site of action is the distal renal tubule. The hypotensive effect is also due to a reduction in peripheral resistance observed mainly in chronic use. Teratogenicity: Chlorthalidone crosses the placental barrier. In general, diuretics are not associated with teratogenicity. A slight association with respiratory malformation has been suggested. Interactions: Chlorthalidone may increase the toxicity of digitalis glycosides by depleting serum potassium concentrations. Due to the potassium depletion, chlorthalidone may enhance the neuromuscular blocking action of competitive muscle relaxants such as tubocurarine or gallamine triethiodide. It may increase the effect of antihypertensive agents such as guanethidine sulfate, methyldopa or ganglionic blocking agents. The postural hypotension due to thiazide diuretic therapy may be increased by concomitant ingestion of alcohol, barbiturates, or opioids. The potassium-depleting effect of thiazides may be enhanced by corticosteroids, corticotrophin, carbenoxolone, and amphotericin B. Chlorthalidone may reduce the response to pressor amines such as norepinephrine, but the clinical significance of this effect is uncertain. Concomitant administration of thiazide diuretics and lithium salts is not recommended since the blood concentration of lithium is increased. By depleting the serum potassium concentration, chlorthalidone may increase the risk of cardiac dysryhthmias (torsades de pointes). The pharmacological effects of oral hypoglycaemic agents may be reduced. Non-steroidal anti-inflammatory drugs may antagonize the diuretic actions of thiazides. The hyperglycemic, hypotensive, and hyperuricaemic effects of diazoxide may be potentiated by thiazides. Probenecid enhances excretion of calcium, magnesium, and citrate during thiazide therapy, but does not affect excretion of sodium, potassium, ammonium chloride, bicarbonate, and phosphate. Thiazides increase urinary pH and may decrease urinary excretion of amphetamines and quinidine. The effects of oral anticoagulants may be decreased when used concurrently with chlorthalidone. Pre-anesthetic and anesthetic drugs used in surgery may be potentiated when used concurrently with chlorthalidone. The effectiveness of methenamine may be decreased when used with chlorthalidone due to alkalinization of the urine. A study in two healthy subjects evidenced that chlorthalidone and acetazolamide competed for the same binding sites on blood cells. Main adverse effects: It may induce hyperglycemia and glycosuria and may aggravate pre-existing diabetes mellitus. Other side-effects include anorexia, gastric irritation, nausea, vomiting, constipation, diarrhea, headache, dizziness, postural hypotension, paraesthesia, impotence, mood and mental changes and yellow vision. Blood dyscrasias include thrombocytopenia, more rarely, granulocytopenia, leucopenia and aplastic anemia. administration of tablets containing thiazides with an enteric-coated core of potassium chloride. Chlorthalidone may cause intense diuresis leading to insomnia in the elderly, because of its long half-life. ANIMAL/PLANT STUDIES: Reproduction studies conducted with rats and rabbits at doses up to 240 times greater than the therapeutic dose have shown no evidence of impaired fertility or harm to the fetus due to chlorthalidone.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

化合物：氯噻嗪酮

Compound:chlorthalidone

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI标注：模糊的DILI关注

DILI Annotation:Ambiguous DILI-concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：2

Severity Grade:2

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

不良反应部分

Label Section:Adverse reactions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 消除途径

大约50%的给药剂量通过肾脏以未代谢的形式排出，排泄特点是由快速相随后缓慢分泌相的双相消除。

Approximately 50% of the administered dose is excreted unmetabolized through the kidney, and excretion is characterized by biphasic elimination with a rapid phase followed by a slow secretory phase.

来源:DrugBank

吸收、分配和排泄

• 分布容积

氯噻嗪已经显示出能够迅速在红细胞内浓缩，随后通过缓慢扩散回到血清部分，导致分布体积增大。

Chlorthalidone has been shown to rapidly concentrate within erythrocytes and subsequently equilibrate via a slow diffusion back into the serum compartment, resulting in a large volume of distribution.

来源:DrugBank

吸收、分配和排泄

生物化学研究表明，药效持久的原因是由于缓慢的胃肠道吸收和肠肝循环。药物以原型通过肾脏排泄。

BIOCHEM STUDIES SUGGEST THAT PROLONGED DURATION OF ACTION IS DUE TO SLOW GI ABSORPTION & ENTEROHEPATIC RECIRCULATION. DRUG IS EXCRETED UNCHANGED BY KIDNEY.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大多数/噻嗪/类药物在3到6小时内迅速排泄。/噻嗪类药物/

MOST /THIAZIDE/ COMPD ARE RAPIDLY EXCRETED WITHIN 3 TO 6 HR. /THIAZIDE COMPD/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氯噻酮剂量依赖性尿排泄研究。

STUDY OF DOSE-DEPENDENT URINARY EXCRETION OF CHLORTHALIDONE.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S22,S24/25
• WGK Germany：
  2
• 海关编码：
  2935009090
• 储存条件：
  本品应当密封并存放在阴凉处。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Chlorthalidone
CAS-No. : 77-36-1
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Eye irritation (Category 2)
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H319 Causes serious eye irritation.
Precautionary statement(s)
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Formula : C14H11ClN2O4S
Molecular Weight : 338,77 g/mol

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Section 4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
Gastrointestinal disturbance, Dermatitis, Nausea, Dizziness, Headache
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx), Sulphur oxides, Hydrogen chloride gas
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Immersion protection
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: > 480 min
Material tested:Dermatril® ( Z677272, Size M)
Splash protection
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: > 30 min
Material tested:Dermatril® ( Z677272, Size M)
data source: KCL GmbH, D-36124 Eichenzell, phone [phone], test method: EN374
If used in solution, or mixed with other substances, and under conditions which differ from EN 374,
contact the supplier of the CE approved gloves. This recommendation is advisory only and must
be evaluated by an Industrial Hygienist familiar with the specific situation of anticipated use by our
customers. It should not be construed as offering an approval for any specific use scenario.
Body Protection
impervious clothing, The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- log Pow: 0,85
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - > 5.000 mg/kg
Skin corrosion/irritation
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
Reproductive toxicity - mouse - Oral
Effects on Fertility: Post-implantation mortality (e.g., dead and/or resorbed implants per total number of
implants).
Reproductive toxicity - Human - male - Oral
Paternal Effects: Impotence.
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion
May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes Causes eye irritation.
Signs and Symptoms of Exposure
Gastrointestinal disturbance, Dermatitis, Nausea, Dizziness, Headache
Additional Information
RTECS: DB1556000

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15 - REGULATORY INFORMATION
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Chlorthalidone (chlortalidone) 是一种利尿剂，用于治疗高血压。它通过抑制钠离子通过肾小管上皮细胞的转运，增加钠、氯和水排泄到肾内腔。主要作用位点是髓袢上升支的皮质稀释段。通过增加钠至远端肾小管的转运，Chlorthalidone 间接利用钠钾交换机制增加钾分泌（即顶端 ROMK/Na 通道耦合基底侧 NKATPases）。

体外研究

Chlorthalidone 是一种噻嗪类利尿剂。口服后，血浆浓度在2-6小时内达到峰值。Chlorthalidone 的半衰期约为42小时（范围29-55小时），长期给药时可延长至45-60小时。个体间的半衰期差异较大。未经改变的 Chlorthalidone 通过肾脏排出体外。Chlorthalidone 的利尿作用在18小时达到最大，并持续超过48小时。研究表明，25毫克每日剂量几乎与较高剂量一样有效，但风险更低，不易引起低钾血症。Chlorthalidone 减少草酸钙结石的复发率，而氢氧化镁则没有这种效果。一项双盲随机对照研究显示，在预防复发性草酸钙肾结石时，Chlorthalidone 或者氢氧化镁的效果得到了检验。实验中每天服用25毫克或50毫克 Chlorthalidone、650毫克或1300毫克氢氧化镁或安慰剂。所有组别与治疗前相比显著减少了结石事件。在安慰剂组，预测的结石事件数量减少了56.1%（P<0.01），而低剂量和高剂量氢氧化镁分别减少了73.9%和62.3%（P<0.001 和 P<0.01 分别）。Chlorthalidone 治疗导致预测结石事件减少 90.1%，不同剂量的效果相似。与安慰剂或无效疗法相比，当给予安慰剂或无效治疗时观察到的显著减少的结石事件数表明了历史对照带来的积极偏差，并强调了适当实验设计的重要性。

化学性质

白色结晶性粉末，熔点224-226℃（分解）。微溶于水、乙醇、氯仿，溶于热乙醇。无臭，无味。

用途

利尿药，用于治疗心源性、肾性和其他水肿症。

生产方法

由2-(3-氨基-4-氯苯甲酰)苯甲酸[118-04-7]经重氮化、置换、氯磺化、环合、胺化而得。

反应信息

• 作为反应物：
  描述：

  氯噻酮 在 sodium hydroxide 作用下， 生成 2-(4-氯-3-氨基磺酰基苯甲酰基)苯甲酸
  参考文献：
  名称：

  用于二苯甲酮-2-羧酸衍生物的构成†

  摘要：

  一些二苯甲酮-2-羧酸

  DOI：

  10.1002/hlca.19590420344
• 作为产物：
  描述：

  4-(4-chlorophenyl)-1H-2,3-benzoxazin-1-one 在 氯磺酸 、 ammonium hydroxide 、 双氧水 、 溶剂黄146 、 sodium hydroxide 、 锌 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 生成 氯噻酮
  参考文献：
  名称：

  [EN] IMPROVED PROCESS FOR THE PREPARATION OF CHLORTHALIDONE
  [FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE CHLORTHALIDONE

  摘要：

  本发明涉及制备氯噻酮的方法。具体来说，所披露的工艺在工业规模上是可行的，并且提供了基本纯净的氯噻酮。

  公开号：

  WO2018158777A1
• 作为试剂：
  描述：

  2,5-二甲基呋喃 、 甲醇 在 氯噻酮 作用下， 以12%的产率得到3-己烯-2,5-二酮
  参考文献：
  名称：

  Vargas, Franklin; Mendez, Pharmazie, 1999, vol. 54, # 12, p. 920 - 922

  摘要：

  DOI：

文献信息

• DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160221965A1

  公开（公告）日：2016-08-04

  The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.

  本申请涉及新颖的2,5-二取代6-(三氟甲基)嘧啶-4(3H)-酮衍生物，其制备方法，其单独或与其他药物联合用于治疗和/或预防疾病，以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管、肾脏、炎症和纤维化疾病。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• [EN] HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF STRESS-RELATED CONDITIONS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES POUR LE TRAITEMENT D'ÉTATS LIÉS AU STRESS
  申请人：OTSUKA PHARMA CO LTD

  公开号：WO2010137738A1

  公开（公告）日：2010-12-02

  The present invention provides a novel heterocyclic compound. A heterocyclic compound represented by general formula (1) wherein, R1 and R2, each independently represent hydrogen; a phenyl lower alkyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group and the like on a benzene ring and/or a lower alkyl group; or a cyclo C3-C8 alkyl lower alkyl group; or the like; R3 represents a lower alkynyl group or the like; R4 represents a phenyl group that may have a substituent(s) selected from the group consisting of a 1,3,4-oxadiazolyl group that may have e.g., halogen or a heterocyclic group selected from pyridyl group and the like; the heterocyclic group may have at least one substituent(s) selected from a lower alkoxy group and the like or a salt thereof.

  本发明提供了一种新颖的杂环化合物。一种由通式（1）表示的杂环化合物，其中，R1和R2分别独立表示氢；苯基较低烷基基团，可能在苯环和/或较低烷基基团上具有从较低烷基基团等组成的取代基；或环C3-C8烷基较低烷基基团；或类似物；R3表示较低炔基基团或类似物；R4表示可能具有从1,3,4-噁二唑基团（例如，卤素）或从吡啶基团等组成的取代基的苯基团；所述杂环基可能具有至少一个从较低烷氧基等选择的取代基或其盐。
• PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
  申请人：Rewcastle Gordon William

  公开号：US20110009405A1

  公开（公告）日：2011-01-13

  Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.

  本文提供了式I的嘧啶基和1,3,5-三嗪基苯并咪唑化合物，以及它们的药物组合物、制备方法，以及作为抗癌治疗药物或药剂的用途，可以单独使用，也可以与放疗和/或其他抗癌药物联合使用。
• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。