水杨酸 | 69-72-7

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 消毒防腐药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 水杨酸
• 中文别名: 2-羟基苯甲酸；柳酸；美沙拉嗪杂质F；柳酸,沙利西酸；邻羟基苯甲酸；升华水杨酸；邻-羟基苯甲酸
• 英文名称: salicylic acid
• 英文别名: 2-hydroxy-1-benzoic acid；o-hydroxybenzoic acid；2-hydroxybenzoic acid；salicyclic acid；2‑hydroxybenzoic acid；hydroxy benzoic acid；2-HBA；2-Carboxyphenolate;hydron；2-carboxyphenolate;hydron
• CAS: 69-72-7
• 化学式: C₇H₆O₃
• mdl: MFCD00002439
• 分子量: 138.123
• InChiKey: YGSDEFSMJLZEOE-UHFFFAOYSA-N

物化性质

• 熔点：
  158-161 °C(lit.)
• 沸点：
  211 °C(lit.)
• 密度：
  1.44
• 蒸气密度：
  4.8 (vs air)
• 闪点：
  157 °C
• 溶解度：
  乙醇：1 Mat 20 °C，透明，无色
• 最大波长(λmax)：
  210nm, 234nm, 303nm
• LogP：
  2.01
• 物理描述：
  Solid
• 颜色/状态：
  White crystals, fine needles, or fluffy white crystalline powder
• 气味：
  SYNTHETIC ACID IS ODORLESS
• 味道：
  Acrid taste
• 蒸汽密度：
  4.8 (Air= 1)
• 蒸汽压力：
  8.2X10-5 mm Hg at 25 °C
• 水溶性：
  -1.82
• 亨利常数：
  Henry's Law constant = 7.3X10-9 atm-cu m/mole at 25 °C (est)
• 稳定性/保质期：
  1. 在空气中稳定，见光会渐渐变色，并且有毒。 2. 常压下急剧加热分解为苯酚和二氧化碳。1克水杨酸可分别溶于460毫升水、15毫升沸水、2.7毫升乙醇、3毫升丙酮、3毫升乙醚、42毫升氯仿、135毫升苯、52毫升松节油、约60毫升甘油和80毫升石油醚中。加入磷酸钠或硼砂等能增加其在水中的溶解度。其水溶液的pH值为2.4。水杨酸与三氯化铁水溶液反应会生成特殊的紫色。 3. 本品刺激皮肤和黏膜，因其能与组织中的蛋白质发生反应而具有腐蚀作用，可导致角膜增殖后剥离。虽然毒性比苯酚弱，但大量服用会引起呕吐、腹泻、头痛、出汗、皮疹、呼吸急促、酸中毒症和兴奋等不适症状；严重时可能会出现呼吸困难、虚脱，最终因心脏麻痹而导致死亡。水杨酸通过肾脏排出，常引起急性肾炎。操作人员应穿戴适当的劳动保护装备。 4. 水杨酸存在于烤烟烟叶、白肋烟烟叶、香料烟烟叶以及烟气中。 5. 在水杨树中有微量存在。
• 自燃温度：
  1004 °F (540 °C)
• 分解：
  When heated to decomp it emits acrid smoke and irritating fumes.
• 腐蚀性：
  Non-corrosive
• 燃烧热：
  3.026 millijoules/mole
• 折光率：
  Index of refraction: 1.565 at 25 °C/D
• Caco2细胞的药物渗透性：
  -4.79
• 解离常数：
  pKa1 = 2.98 at 20 °C (carboxylic acid); pKa2 = 13.6 (phenol)
• 碰撞截面：
  123.36 Ų [M-H]- [CCS Type: DT, Method: stepped-field]
• 保留指数：
  1308 ;1308 ;1330 ;1266 ;1277 ;1296 ;1305 ;1291 ;1263 ;1308 ;1330 ;1330

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

水杨酸被广泛代谢。

Salicylic acid is extensively metabolized.

来源:DrugBank

代谢

在低剂量时，大约80%的水杨酸在肝脏中被代谢。与甘氨酸结合形成水杨尿酸，与葡萄糖醛酸结合则形成酰基和酚醛葡萄糖苷酸。少量的水杨酸也会被羟基化成龙胆酸。在大剂量时，动力学从一级反应转变为零级反应。

At low dosage, approximately 80% of salicylic acid is metabolized in the liver. Conjugation with glycine, forms salicyluric acid and when conjugated with glucuronic acid, acyl and phenolic glucuronide are formed. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large doses, the kinetics switch from first order to zero order.

来源:Hazardous Substances Data Bank (HSDB)

代谢

狗通过静脉注射了含有1克(14)C水杨酸（含10微居里）的碳酸氢钠溶液。收集尿液30至36小时。从一只代表性动物中回收的尿液中代谢物为：50%未变化的水杨酸，25%葡萄糖苷酸，10%水杨尿酸，以及4%至5%的龙胆酸。总回收量超过剂量的90%。

Dogs were dosed intravenously with 1 g (14)C-salicylic acid (containing 10 uCi) in sodium bicarbonate solution. Urine was collected for 30 to 36 hours. Urinary metabolite recovery from one animal, which was representative of all the dosed animals, was 50% unchanged salicylic acid, 25% glucuronates, 10% salicyluric acid, and 4% to 5% gentisic acid. Total recovery was > 90% of the dose.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在局部给药后识别出的主要尿液代谢物与口服水杨酸盐给药后的不同；那些来自经皮吸收的含有更多的水杨酸葡萄糖苷酸（42%）和较少的水杨尿酸（52%）和水杨酸（6%）。

The major urinary metabolites identified after topical administeration differ from those after oral salicylate adminisration; those derived from percutaneous absorption contain more salicylate glucuronides (42%) and less salicyluric (52%) and salicylic acid (6%).

来源:Hazardous Substances Data Bank (HSDB)

代谢

在人体中产生O-羧基苯基-B-D-葡萄糖苷酸；在兔中；在大鼠中产生O-羧基苯基硫酸盐。/来自表格/

YIELDS O-CARBOXYPHENYL-B-D-GLUCURONIDE IN MAN; IN RABBIT; YIELDS O-CARBOXYPHENYL SULFATE IN RAT. /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别:水杨酸是一种止痛药和退热药。水杨酸以酯的形式存在于多种植物中，尤其是在冬青叶和甜桦树皮中。它是通过加热钠酚酸盐和二氧化碳，以及微生物氧化萘制得的。水杨酸是无色或白色的晶体。无色针状晶体或白色结晶粉末。合成形式为白色，但如果由天然甲基水杨酸制备，可能略带黄色或粉红色。水杨酸是带有甜味的刺激性白色结晶粉末。如果用天然甲基水杨酸制备，它可能带有淡薄荷味。它有药膏、乳膏、凝胶、贴剂、液体和石膏等形式。水杨酸易溶于水、沸水、酒精、醚和氯仿。水杨酸具有角质溶解性质，用于治疗过度角化和鳞屑性皮肤病，如头皮屑、鱼鳞病和银屑病。最初使用2%的浓度，如有必要，可增至约6%。它常与其他许多药物联合使用，如苯甲酸、煤焦油、间苯二酚和硫。水杨酸还以涂料和火棉胶基(10至17%)或作为贴剂(20至50%)的形式用于破坏疣和鸡眼。它还具有杀菌作用，用于治疗真菌性皮肤病，如癣。人类暴露:主要风险和靶器官:水杨酸和柳酸盐的毒性作用复杂。口服治疗剂量主要的危险是胃肠道刺激。肝性脑病(赖氏综合症)在服用阿司匹林治疗病毒感染(如流感)的儿童中有报道。水杨酸盐的毒性剂量刺激呼吸中枢，导致呼吸性碱中毒。在严重中毒时，代谢性酸中毒、水和电解质丢失是主要的次要后果。中枢神经系统毒性包括耳鸣、听力损失，在非常严重的情况下，尤其是在儿童中，可能会出现抽搐和昏迷。靶器官是中枢神经系统、肺、肾和肝。临床效果总结:口服水杨酸和其他水杨酸盐后，常见的症状包括恶心、呕吐、上腹痛、耳鸣、听力损失、出汗、潮红(血管扩张)、呼吸急促和过度换气。水杨酸的局部胃肠道刺激比阿司匹林更明显。在严重中毒时，可能出现易怒、震颤、视力模糊、精神混乱、谵妄、昏迷、发热、脑水肿和心肺骤停。中枢神经系统毒性和胃肠道出血在慢性(治疗性)中毒后更常见。从呼吸性碱中毒到代谢性酸中毒的酸碱平衡明显改变可能会出现。在成人严重水杨酸盐中毒时，可能出现非心源性肺水肿、非局部性神经系统异常、无法解释的酮症酸中毒和凝血酶原时间延长。皮肤疹和结膜下出血可能出现，但严重的血小板减少症很少见。甲基水杨酸中毒的气味可以在呼吸、尿液和呕吐物中检测到。中枢神经系统刺激、剧烈过度换气和发热是突出的特征。诊断:水杨酸过量的症状和体征通常以恶心、呕吐和上腹痛开始。然而，在轻度水杨酸盐中毒，尤其是治疗性中毒时，耳鸣、听力损失、头晕、出汗和潮红更常见。严重水杨酸盐中毒与明显的呼吸和神经系统毒性有关。成人更常见的是呼吸急促和呼吸性碱中毒，而儿童更常见的是呼吸不足和代谢性酸中毒。尿液中水杨酸盐的快速筛查试验可能表明使用了该药物。血浆/血清中水杨酸盐浓度的测定可以确认诊断并揭示中毒的严重程度。由于水杨酸对胃的严重刺激，它不再口服使用。然而，当局部使用时，它可能会引起一些人的过敏性接触性皮炎。如果涂在大面积皮肤上，它可能会被吸收到血液中并引起水杨酸盐中毒。进入途径:口服:水杨酸会引起胃刺激，因此没有口服药物。然而，含有67%甲基水杨酸的中医药油口服。皮肤:水杨酸容易从皮肤吸收并可能引起毒性(水杨酸盐中毒)。动力学:按暴露途径的吸收:水杨酸容易从皮肤吸收，在儿童和新生儿中可能引起毒性。含有甲基水杨酸的草药产品，如中医药油，也可以通过口服后吸收到胃肠道粘膜。按暴露途径的分布:血液中大约50%到80%的水杨酸盐与血浆蛋白结合，其余的保持活性离子态；蛋白结合取决于浓度。结合位点的饱和导致更多的自由水杨酸盐和增加的毒性。表观分布容积为0.1至0.2 L/kg。酸中毒增加水杨酸的分布容积，因为组织渗透性增加。按暴露途径的生物半衰期:治疗剂量后，血浆水杨酸盐的半衰期为2至4.5小时，但在过量服用时，可增至18至36小时。当代谢途径饱和(与甘氨酸结合)时，应用零级动力学，因此不能正确

IDENTIFICATION: Salicylic acid is an analgesic and antipyretic medication. Salicylic acid in the form of esters was found in several plants, notably in wintergreen leaves and the bark of sweet birch. It was made synthetically by heating sodium phenolyate with carbon dioxide under pressure and microbial oxidation of naphthalene. Salicylic acid is colorless or white crystals. Colourless acicular crystals or a white crystalline powder. The synthetic form is white but if prepared from natural methyl salicylate, it may have a slightly yellow or pink tint. Salicylic acid is a white crystalline powder with a sweetish acrid taste. If prepared from natural methyl salicylate, it may have a faint mint like odor. It is available in forms of ointments, cream, gel, transdermal patches, liquids and plaster. Salicylic acid is soluble in water, boiling water, alcohol, ether and chloroform. Salicylic acid has keratinolytic properties and is applied topically in the treatment of hyperkeratotic and scaling conditions such as dandruff, ichthyosis and psoriasis. Initially a concentration of 2% is used increasing to about 6% if necessary. It is often used in conjunction with many other agents, such as benzoic acid, coal tar, resorcinol and sulfur. Salicylic acid is also used in the form of paint and in the form of collodion basis (10 to 17%) or as a plaster (20 to 50%) to destroy warts and corns. It also possesses fungicidal properties and is used topically in the treatment of fungal skin infections such as tinea. HUMAN EXPOSURE: Main risks and target organs: The toxic effects of salicylic acid and salicylates are complex. Main risks with oral therapeutic doses are mostly gastrointestinal irritation. Hepatic encephalopathy (Reye's Syndrome) has been reported in children who had taken aspirin for treatment of viral infections such as influenza. Toxic doses of salicylate stimulate the respiratory centre leading to respiratory alkalosis. In severe intoxication, metabolic acidosis, water and electrolyte loss occur as the principle secondary consequences. Central nervous system toxicity includes, tinnitus, hearing loss and in very severe cases particularly in children convulsions and coma. Target organs are central nervous system, lungs, kidneys and liver. Summary of clinical effects: Following oral ingestion of salicylic acid and or any other salicylate, nausea, vomiting, epigastric discomfort, tinnitus, loss of hearing, sweating, flushing (vasodilatation) tachypnea and hyperpnea are commonly observed. Local gastrointestinal (GI) irritation of SA is more marked than ASA (acetylsalicylic acid). In severe intoxication irritability, tremor, blurred vision, mental confusion, delirium, stupor, coma, fever, cerebral edema and cardiorespiratory arrest may occur. Central nervous system toxicity and gastrointestinal haemorrhage are more common after chronic (therapeutic) intoxication. A marked alteration of acid base balance from respiratory alkalosis to metabolic acidosis may be observed. In severe salicylate intoxication in adults, non cardiogenic pulmonary edema, nonfocal neurological abnormalities, unexplained ketosis and a prolonged prothrombin time can occur. Skin eruption and subconjunctival hemorrhage may be seen but marked thrombocytopenia is rare. Methyl salicylate poisoning has the odor of the drug which can be detected on the breath and in the urine and vomit. Central nervous system stimulation, intense hyperpnea and hyperpyrexia are prominent features. Diagnosis: Symptoms and signs of oral ingestion of salicylic acid overdose usually commence by nausea, vomiting and epigastric discomfort. However, in mild salicylism particularly with therapeutic intoxication, tinnitus, loss of hearing, dizziness, sweating, and flushing are more common. Severe salicylate poisoning is associated with marked respiratory and nervous system toxicity. Hyperventilation and respiratory alkalosis are more common in adults, whereas hypoventilation and metabolic acidosis are more commonly observed in children. A rapid screening test for the presence of salicylate in the urine may indicate the use of the drug. Estimation of salicylate concentration in plasma/serum can confirm the diagnosis and reveals the severity of intoxication. Due to the severe gastric irritation which salicylic acid causes, it is no longer used orally. However, when used topically it may cause an allergic contact rash in some people. If applied to large areas of skin, it may be absorbed into the blood stream and induce salicylism. Routes of entry: Oral: Salicylic acid causes gastric irritation and thus, there is no oral pharmaceutical available. However, Chinese medicated oil which contains 67% methyl salicylate has been taken orally. Dermal: Salicylic acid is readily absorbed from the skin and may induce toxicity (salicylism). Kinetics: Absorption by route of exposure: Salicylic acid is readily absorbed from the skin and may cause toxicity, particularly in children and the newborn. Herbal products such as the chinese medicated oil which contains methyl salicylate is also absorbed through gastrointestinal mucosa following ingestion. Distribution by route of exposure: About 50 to 80% of salicylate in the blood is bound to plasma proteins, while the rest remains in the active ionized state; protein binding is concentration dependent. Saturation of binding sites lead to more free salicylate and increased toxicity. The apparent volume of distribution is 0.1 to 0.2 L/kg. Acidosis increases the volume of distribution because of the enhancement of tissue penetration of salicylate. Biological half-life by route of exposure: The plasma salicylate half-life following therapeutic doses is 2 to 4.5 hours, but in over-dosage, increases to 18 to 36 hours. When the metabolic pathway is saturated (conjugation with glycin), zero order kinetics apply and thus the elimination half-life cannot be derived correctly. Metabolism: At low dosage, approximately 80% of salicylic acid is metabolized in the liver. Conjugation with glycine, forms salicyluric acid and when conjugated with glucuronic acid, acyl and phenolic glucuronide are formed. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large doses, the kinetics switch from first order to zero order (Michaelis-Menten) kinetics. Elimination and excretion: Salicylates are excreted mainly by the kidney as salicylic acid, salicyluric acid, salicylic glucuronides and gentisic acid. The proportion excreted of each metabolite, depends upon urinary pH. With urinary alkalinisation, salicylic acid excretion is enhanced. Mode of action: Toxicodynamics: Marked hyperventilation occurs as a result of direct stimulation of the respiratory centre. Indirect stimulation of respiration is caused by an increased production of CO2 as a result of salicylate-induced uncoupling of oxidative phosphorylation. Respiratory alkalosis develops as a result of the direct and indirect stimulation of the respiratory centre. In an attempt to compensate, bicarbonate accompanied by sodium, potassium and water, is excreted in the urine. Dehydration and hypokalemia result, but more importantly, the loss of bicarbonate diminishes the buffering capacity of the body and allows the development of a metabolic acidosis. The pyretic effect of toxic doses of salicylate is a direct result of the uncoupling of oxidative phosphorylation. High doses of salicylate have additional toxic effects on the central nervous system consisting of stimulation(including convulsions) followed by depression, confusion, dizziness, asterixis, delirium, psychosis, stupor and coma. Very high doses have depressive effect on the medulla and may cause central respiratory paralysis as well as sudden circulatory collapse secondary to vasomotor depression. The loss of buffering capacity and the effects of salicylate on carbohydrate, lipid and protein metabolism lead to the development of a metabolic acidosis or, more commonly in practice, a mixed acid base disturbance. Both hypo-and hyperglycemia may occur in salicylate poisoning. The former most probably due to an increased tissue demand for glucose oxidation due to the uncoupling of oxidative phosphorylation. Neuroglycopenia can occur in the presence of normal blood glucose concentrations. If hepatic glycogen stores are adequate, catecholamines production stimulates glycogenolysis leading to hyperglycemia which can persist for several days. Salicylate intoxication is often accompanied by hypothrombinemia due to a warfarin like action of salicylate on the vitamin K1 epoxide cycle, which rarely causes clinical problems. Pharmacodynamics: Salicylic acid alleviates pain, lowers an elevated body temperature and inflammation by inhibiting the synthesis of prostaglandins that occur in inflamed tissues. Salicylate inhibits the conversion of arachidonic acid to the unstable endoperoxide intermediate PG G2, which is catalyzed by the enzyme cyclo oxygenase. Platelets are especially susceptible to this action as they are incapable of regenerating the enzyme, presumably they have little or no capacity for protein biosynthesis. Cyclooxygenase(COX) is present in two main isoforms. COX-1 is the isoform of the enzyme and is present under normal physiological conditions. COX-2 is the inducible isoform of the enzyme and is induced in settings of inflammation (production of eicosanoids and kinins). Inhibition of COX-1 results in unwanted side effects, particularly those leading to gastric ulcer. Adults: Since salicylic acid is available only in topical preparations, human data on toxicity have not been reported. However, the chinese medicated oil, which contains 67% methyl salicylate induced severe salicylate poisoning. Salicylic acid concentrations above 800 mg/L after 6 hours post exposure is severely toxic and may be lethal. Children: Salicylate intoxication is often more serious in small children (1-4 years) than in older children, due to an early development of a metabolic acidosis rather than a respiratory alkalosis. Teratogenicity: There is no evidence that moderate therapeutic doses of salicylates cause fetal damage in human beings; however, babies born to women who ingest salicylates for long periods may have a significantly reduced mass at birth. In addition, there is an increase in prenatal mortality, anemia, antepartum and postpartum haemorrhage, prolonged gestation and complicated deliveries. These effects occur when salicylates are administered during the third trimester, and thus its use during this period of pregnancy should be avoided. Interactions: Salicylic acid is highly protein-bound and may increase the unbound or free drug concentrations of other drugs such as hypoglycemics, anticoagulants and methotrexate(an antimetabolite chemotherapeutic drug), reaching toxic levels of these agents. The uricosuric activity of phenylbutazone, probenecid and sulphinpyrazone is strongly antagonized by salicylate and maybe completely diminished by small doses due to decreased tubular reabsorption of uric acid. In a report of two cases of severe salicylate poisoning, asystole occurred shortly after the intravenous administration of diazepam. Main adverse effects: Salicylic acid is a gastric irritant and because of the serious damage it may cause to the stomach lining, it has not been used orally. Topical use of salicylic acid may induce allergic contact dermatitis. Salicylic acid may cause excessive drying and irritation in some people. Some individuals, especially asthmatics exhibit sensitivity to salicylates. Urticaria, angioneurotic oedema, rhinitis, severe and even fatal paroxysmal, bronchospasm and dyspnea may occur. Acute poisoning: Ingestion: Initial symptoms of salicylate poisoning may be nausea and vomiting, epigastric pain and occasionally haematemesis. Hyperventilation, sweating, flushing, fever, irritability, tinnitus and loss of hearing are the common clinical features of mild to moderate salicylate intoxication. In severe intoxication, hypoventilation, stupor, hallucination, convulsions, papilledema and coma particularly in children may occur. Metabolic acidosis, non-cardiogenic pulmonary edema, hepatotoxicity and cardiac dysrhythmias may also occur. Skin exposure: Severe poisoning has been reported as a result of the use of salicylic acid ointment for dermatological problems and in the treatment of skin burns. Chronic poisoning: Ingestion: Chronic salicylate poisoning occurred as a result of excessive therapeutic administration over a period of 12 hours or more were reported. Metabolic pathways of salicylic acid become saturated and thus plasma concentration increases, producing toxicity. Small children are at particular risk of overdose especially when fever, sweating and tachycardia of salicylate intoxication are attributed to the underlying illness and are used as indications for increasing the dose. Children may become intoxicated through breast milk. The presenting signs of chronic salicylate poisoning can include metabolic acidosis, hypoglycemia, lethargy, coma and fits. Skin exposure: Chronic usage of salicylic acid and or methyl salicylate in skin and rheumatic diseases may cause intoxication through percutaneous absorption. Life threatening salicylate poisoning caused by percutaneous absorption of salicylic acid (10% ointment) in a 7-year old boy with ichthyosis vulgaris was reported. Application of teething gels containing salicylic acid induced intoxication. Course, prognosis, cause of death: If a large quantity of a salicylate has been taken, nausea, vomiting, tinnitus, deafness, sweating, vasodilatation and hyperventilation may develop. Acid-base disturbances, electrolyte imbalance, non cardiogenic pulmonary edema, hypoventilation and hallucination, stupor, irritability, coma and convulsions particularly in children and older patients can proceed death. Loss of consciousness in adults is very rare and when occurs indicates poor prognosis. A review of 51 fatal cases of acute salicylate poisoning in Ontario during 1983 and 1984, discovered that salicylate was the most common cause of death, due to the ingestion of single drugs. Autopsy results showed that 50% of the patients had pulmonary abnormalities, 28% had lesions of the gastrointestinal tract, 18% had nervous system abnormalities and 25.6% had no pathological changes. Mortality from chronic salicylate intoxication is considerably higher (25%) than from acute overdose (1 to 2%). Death is often due to sudden cardiac arrest or occasionally due to multiple complications following severe brain damage. Systemic description of clinical effects: Cardiovascular: Sudden cardiovascular collapse is a recognized complication of salicylate poisoning. Two patients with severe salicylate intoxication developed asystole shortly after intravenous diazepam administration. Transient myocardial dysfunction (global left ventricular shortening fraction of 23%) with pulmonary edema was found in a 13-month-old boy with salicylate poisoning. Respiratory: Non-cardiogenic pulmonary edema may occur in salicylate intoxicated patients who are over 30 years of age. Cigarette smoking, chronic salicylate ingestion, metabolic acidosis and the presence of neurological symptoms and signs on admission are strong risk factors for the subsequent development of pulmonary edema. The exact mechanism is unknown. Three possible explanations are: (1) A direct toxic effect on pulmonary microvasculature; (2) Interaction with endogenous mediators such as prostaglandins; and (3) A central nervous system mediated effect. Neurological: Central Nervous System (CNS): In moderate to severe salicylate intoxication, CNS stimulation (irritability and convulsions) followed by depression, confusion, dizziness, delirium, psychosis, asterixis, stupor and coma occur usually when metabolic acidosis is the dominant acid-base abnormality. These features are thought to be due to reduced ionisation of salicylic acid and a shift of salicylate from the plasma into the brain. Very high doses of salicylate have a depressive effect on the medulla and may cause central respiratory paralysis as well as sudden circulatory collapse, secondary to vasomotor depression. Gastrointestinal: Ingestion of salicylate may result in epigastric discomfort, nausea and vomiting. Salicylic acid has more irritant effects on gastric mucosa than acetylsalicylic acid and thus has been withdrawn from oral administration for many years. Acetylsalicylic acid may also cause gastric irritation. Perforated peptic ulcer also occurs extremely rarely. Hepatic: Hepatotoxicity may occur both after the therapeutic use of salicylate or following its over-dosage. Liver biopsy revealed acute hepatocellular necrosis with periportal inflammation and fatty changes in hepatocytes. Hepatic encephalopathy (Reye's Syndrome) has been reported in children taking aspirin for treatment of viral infections such as influenza. Urinary: Renal: Oliguria sometimes occurs, which is mostly due to dehydration. Renal failure may rarely occur in individuals without volume depletion, pre-existing renal and or systemic diseases. Endocrine and reproductive systems: High doses of salicylate cause release of adrenaline from the adrenal medulla; this is thought to be partly responsible for the observed hypoglycaemia due to glycogenolysis that sometimes occurs. Large doses of salicylate stimulate corticosteroids secretion by the adrenal cortex. Dermatological: Toxic epidermal necrosis in 13 patients associated with the use of salicylate have been reported. Eye, ear, nose, throat: local effects: Eye: Transient myopia occurred in a patient following ingestion of acetylsalicylic acid. Bilateral subconjunctival hemorrhage has been reported. Ear: Tinnitus and hearing loss caused by salicylate in overdose are due to increased labyrinthine pressure. It may also be due to an effect on the hair cells of the cochlea. There is a relationship between the hearing loss and the plasma salicylate concentration. Hematological: Salicylates prolong the bleeding time due to inhibition of collagen glucosyltransferase present in membranes of platelets. As a result, the adherence of platelets to connective tissue or collagen fibres is diminished. Salicylate overdose reduces the concentration of vitamin K-dependent coagulation factors, particularly prothrombin. Immunological: Salicylates have the capacity to supress a variety of antigen-antibody reactions such as: the inhibition of antibody production, of antigen-antibody aggregation and of antigen induced release of histamine. Salicylates also induce a non specific stabilization of capillary permeability during immunological insults. The concentration of salicylate causing this effect is high, and their relationship to the antirheumatic efficacy of salicylates is yet to be determined. Metabolic: Acid-base disturbances: Respiratory alkalosis is more often observed in adults than in children. Metabolic acidosis develops sooner in children than in adults. However, in severe salicylate poisoning in adults, metabolic acidosis may also occur. The acidosis is not therefore due to the presence of salicylic acid itself. The principle cause is competitive inhibition of NAD+-dependent dehydrogenases including lactate and oxoglutarate dehydrogenase and the other oxidative enzymes such as succinate dehydrogenase. Salicylate enhances entry and oxidation of fatty acids in liver cells,leading to increased ketogenesis. Competitive inhibition of amino acyl-tRNA synthetases in pairs and amino acid incorporation results in amino-acidemia. Dehydration and vasomotor depression results in poor renal perfusion and accumulation of sulfuric and phosphoric acids. Fluid and electrolyte disturbances: Increased renal secretion of sodium, potassium and water accompanies loss of bicarbonate in the urine. Fluid loss also results from vomiting, sweating and hyperventilation. Dehydration is commonly associated with hypernatremia. (1) Oxidative Phosphorylation: The uncoupling of oxidative phosphorylation by salicylate results in the inhibition of a number of ATP-dependent reactions and an increase in O2 uptake and CO2 production. (2) Nitrogen compound metabolism: Toxic doses of salicylate cause a significant nitrogen imbalance, characterized by amino aciduria, though this is due in part to stimulation of active tubular absorption because of reduced ATP formation. Fat metabolism: Salicylates enhance oxidation of fatty acids in muscle, liver and other tissues together with a decrease of concentrations of plasma, free fatty acids, phospholipids and cholesterol. Allergic reactions: Some people particularly asthmatics, exhibit marked sensitivity to salicylate, resulting in various reactions including urticaria and other skin eruptions, angioneuritis, oedema, rhinitis and severe and even fatal paroxysmal bronchospasm and dyspnea, hypotension, shock and syncope. Despite the fact that the symptoms (such as the ones mentioned above) resemble anaphylaxis, this reaction does not appear to be immunological in nature. It may be a shunt towards the lipoxygenase pathway leading to an increased production of leukotrienes and other inflammatory mediators. Although, this hypothesis is unproved and it does not explain why only a minority of patients with asthma or other predisposing conditions display the reaction. Even so, results in a small number of patients suggest that blockade of 5-lipoxygenase with the drug zileuton may prevent symptoms and signs of aspirin intolerance. Other clinical effects: The relationship between the use of salicylate and Reye's syndrome in children and adolescents (mostly 5 to 15 years) has been demonstrated by epidemiological studies. Special risks: Salicylate intoxication may occur through placental transfer and breast milk.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

水杨酸直接且不可逆地抑制两种环氧合酶（COX-1和COX-2）的活性，以减少由花生四烯酸形成的前列腺素和血栓素前体的生成。水杨酸盐可能通过竞争性抑制前列腺素的生成。水杨酸盐的抗风湿（非甾体抗炎）作用是其镇痛和抗炎机制的产物。水杨酸是许多护肤产品中的关键成分，用于治疗痤疮、银屑病、老茧、鸡眼、毛发角化病和疣。它通过使表皮细胞更容易脱落，防止毛孔堵塞，为新细胞生长提供空间而起作用。由于其对皮肤细胞的影响，水杨酸也用于治疗头皮屑的几种洗发水中。水杨酸还用作去除寻常疣（足底疣）的凝胶中的活性成分。水杨酸与烟酰胺腺嘌呤二核苷酸（NAD）竞争性地抑制尿苷-5-二磷酸葡萄糖（UDPG）的氧化，与非竞争性地与UDPG抑制。它还竞争性地抑制尿苷-5-磷酸葡萄糖醛酸（UDPGA）的葡萄糖醛酸基团转移到酚类受体上。水杨酸盐的伤口愈合延缓作用可能主要由于其抑制粘多糖合成的抑制作用。

Salicylic acid directly and irreversibly inhibits the activity of both types of cyclo-oxygenases (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. Salicylate may competitively inhibit prostaglandin formation. Salicylate's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms. Salicylic acid is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts. It works by causing the cells of the epidermis to slough off more readily, preventing pores from clogging up, and allowing room for new cell growth. Because of its effect on skin cells, salicylic acid is used in several shampoos used to treat dandruff. Salicylic acid is also used as an active ingredient in gels which remove verrucas (plantar warts). Salicylic acid inhibits the oxidation of uridine-5-diphosphoglucose (UDPG) competitively with nicotinamide adenosine dinucleotide (NAD) and noncompetitively with UDPG. It also competitively inhibits the transferring of glucuronyl group of uridine-5-phosphoglucuronic acid (UDPGA) to the phenolic acceptor. The wound-healing retardation action of salicylates is probably due mainly to its inhibitory action on mucopolysaccharide synthesis.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

作为诱变剂和生殖效应物进行了调查。

Investigated as a mutagen and reproductive effector.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：目前没有关于在母乳喂养期间在皮肤上使用水杨酸的临床信息。由于它不太可能被显著吸收或出现在母乳中，因此被认为在母乳喂养期间使用是安全的。避免将其涂抹在可能与婴儿皮肤直接接触的身体部位，或婴儿可能通过舔舐而摄入药物的地方。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:No information is available on the clinical use of salicylic acid on the skin during breastfeeding. Because it is unlikely to be appreciably absorbed or appear in breastmilk, it is considered safe to use during breastfeeding. Avoid application to areas of the body that might come in direct contact with the infant's skin or where the drug might be ingested by the infant via licking. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

• 消除途径

大约10%以原形从尿液中排出。

About 10% is excreted unchanged in the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

分布容积大约为170毫升/千克体重。

The volume of distribution is about 170 mL/kg of body weight.

来源:DrugBank

吸收、分配和排泄

进行了一项单中心、单序列、两周期交叉研究，以比较九名健康男性和女性受试者面部涂抹30%水杨酸化妆品皮肤剥离配方5分钟和口服650毫克阿司匹林后水杨酸的系统性暴露。水杨酸平均（SD）最大浓度（C(max)）分别为0.81（0.32）ug/mL和56.4（14.2）ug/mL。基于AUC的安全性裕度比率为50:1。在涂抹皮肤剥离溶液的过程中观察到了储库效应，因为水杨酸的吸收在5分钟的应用期后仍在继续。涂抹后1.4至3.5小时达到血浆水杨酸C(max)值，口服阿司匹林后0.5至1.5小时达到。本研究中的血浆浓度（30%；5分钟）与涂抹在同一身体表面积的留宿产品中的低浓度（2%）相似。

A single-center, single-sequence, two-period crossover study was performed to compare the systemic exposure to salicylic acid following facial application of a 30% salicylic acid cosmetic skin peel formulation applied for 5 min and an oral dose of 650 mg aspirin in nine healthy male and female subjects. The mean (SD) maximum salicylic acid concentration (C(max)) was 0.81 (0.32) ug/mL and 56.4 (14.2) ug/mL. The AUC-based safety margin ratio was 50:1. A depot effect was observed during topical application of the skin peel solution as the absorption of salicylic acid continued beyond the 5-min application period. Plasma salicylic acid C(max) values were achieved from 1.4 to 3.5 hr after topical application and from 0.5 to 1.5 hr after oral aspirin. The plasma concentrations in the present study (30%; 5 min) were similar to that of a low concentration (2%) applied in a leave-on product to the same body surface area.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

试剂级水杨酸通过腹部豚鼠皮肤的吸收情况进行了研究。腹部区域被剃毛，并应用了一个循环装置来确定吸收速率。pH值为3.0的水杨酸在浓度为250、400和1000微克/毫升时，吸收速率保持恒定（大约为4%）。浓度为500微克/毫升的水杨酸被用来研究吸收率与pH值的关系。从1到6小时内的吸收百分比分别为：pH值为2、3、4、5时分别为6.1、3.3、0.6和0，而pH值为7、8、9、10时分别为0、1.8、8.0和15.5。

The absorption of reagent-grade salicylic acid through abdominal guinea pig skin was examined. The abdominal area was shaved and a recirculation apparatus was applied to determine the rate of absorption. Salicylic acid, pH 3.0, had a constant rate of absorption (approximately 4%) at concentrations of 250, 400, and 1000 ug/mL. Salicylic acid at a concentration of 500 ug/mL was used to examine the absorption as a function of pH. The percent absorbed from 1 to 6 hours was 6.1, 3.3, 0.6, and 0 at pH 2, 3, 4, and 5, respectively, and 0, 1.8, 8.0, and 15.5 at pH 7, 8, 9, and 10, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

水杨酸能迅速从完整的皮肤中被吸收，尤其是当它被涂在油性的洗剂或软膏中时。

Salicylic acid is rapidly absorbed from the intact skin, especially when applied in oily liniments or ointments, ... .

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S26,S37/39,S39
• 危险类别码：
  R22,R36/37/38,R41
• WGK Germany：
  1
• 海关编码：
  2918211000
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  VO0525000
• 包装等级：
  Z01
• 危险标志：
  GHS05,GHS07
• 危险性描述：
  H302,H318
• 危险性防范说明：
  P280,P301 + P312 + P330,P305 + P351 + P338 + P310
• 储存条件：
  1. 应贮存于阴凉、通风且干燥的库房中，远离火源和热源，并与其他易爆品及氧化剂分开存放。 2. 包装应采用内衬塑料袋，并外套麻袋或聚丙烯编织袋或纤维板桶进行封装。 3. 与爆炸物和氧化剂隔离，并避免光照保存。

SDS

第一部分：化学品名称

化学品中文名称：	邻羟基苯甲酸；水杨酸
化学品英文名称：	Salicylic acid；o-Hydroxybenzoic acid
中文俗名或商品名：
Synonyms：
CAS No.：	69-72-7
分子式：	C 7 H 6 O 3
分子量：	167.12

第二部分：成分/组成信息

纯化学品 混合物

化学品名称：邻羟基苯甲酸；水杨酸

有害物成分 含量 CAS No.

第三部分：危险性概述

危险性类别：
侵入途径：	吸入 食入
健康危害：	本品粉尘对呼吸道有刺激性，吸入后引起咳嗽和胸部不适。对眼有刺激性，长时间接触可致眼损害。长时间或反复皮肤接触可引起皮炎，甚至发生灼伤。摄入发生胃肠道刺激、耳鸣及肾损害。
环境危害：	对环境有危害，对水体和大气可造成污染。
燃爆危险：	本品可燃，具刺激性。

第四部分：急救措施

皮肤接触：	脱去污染的衣着，立即用大量流动清水彻底冲洗至少r5分钟。就医。
眼睛接触：	立即翻开上下眼睑，用流动清水或生理盐水冲洗至少15分钟。就医。
吸入：	迅速脱离现场至空气新鲜处。保持呼吸道通畅。呼吸困难时给输氧。呼吸停止时，立即进行人工呼吸。就医。
食入：	给饮牛奶或蛋清。就医。

第五部分：消防措施

危险特性：	遇高热、明火或与氧化剂接触，有引起燃烧的危险。
有害燃烧产物：	一氧化碳、二氧化碳。
灭火方法及灭火剂：	雾状水、泡沫、二氧化碳、干粉、砂土。
消防员的个体防护：	消防人员须佩戴防毒面具、穿全身消防服，在上风向灭火。
禁止使用的灭火剂：
闪点(℃)：	157
自燃温度(℃)：	引燃温度(℃)：540
爆炸下限[%(V/V)]：	无资料
爆炸上限[%(V/V)]：	无资料
最小点火能(mJ)：
爆燃点：
爆速：
最大燃爆压力(MPa)：
建规火险分级：

第六部分：泄漏应急处理

应急处理：

隔离泄漏污染区，周围设警告标志，切断火源。应急处理人员戴正压自给式呼吸器，穿一般消防防护服。不要直接接触泄漏物，在确保安全情况下堵漏。避免扬尘，用清洁的铲子收集于干燥洁净有盖的容器中，运至废物处理场所。如大量泄漏，收集回收或无害处理后废弃。

第七部分：操作处置与储存

操作注意事项：	密闭操作，局部排风。操作人员必须经过专门培训，严格遵守操作规程。建议操作人员佩戴自吸过滤式防尘口罩，戴化学安全防护眼镜，穿防毒物渗透工作服，戴橡胶手套。远离火种、热源，工作场所严禁吸烟。使用防爆型的通风系统和设备。避免产生粉尘。避免与氧化剂、碱类接触。搬运时要轻装轻卸，防止包装及容器损坏。配备相应品种和数量的消防器材及泄漏应急处理设备。倒空的容器可能残留有害物。
储存注意事项：	储存于阴凉、通风的库房。远离火种、热源。保持容器密封。应与氧化剂、碱类等分开存放，切忌混储。配备相应品种和数量的消防器材。储区应备有合适的材料收容泄漏物。

第八部分：接触控制/个体防护

最高容许浓度：	中 国 MAC：未制订标准前苏联 MAC：未制订标准美国TLV—TWA：未制订标准
监测方法：
工程控制：	密闭操作，局部排风。
呼吸系统防护：	空气中浓度较高时，戴面具式呼吸器。紧急事态抢救或撤离时，建议佩戴自给式呼吸器。
眼睛防护：	戴化学安全防护眼镜。
身体防护：	穿防酸碱工作服。
手防护：	戴防化学品手套。
其他防护：	工作后，淋浴更衣。注意个人清洁卫生。定期体检。

第九部分：理化特性

外观与性状：	白色针状晶体或毛状结晶性粉末。
pH：
熔点(℃)：	160
沸点(℃)：
相对密度(水=1)：	1．44
相对蒸气密度(空气=1)：	4．8
饱和蒸气压(kPa)：	0．17(114℃)
燃烧热(kJ/mol)：
临界温度(℃)：	升华点(℃)：76
临界压力(MPa)：
辛醇/水分配系数的对数值：
闪点(℃)：	157
引燃温度(℃)：	引燃温度(℃)：540
爆炸上限%(V/V)：	无资料
爆炸下限%(V/V)：	无资料
分子式：	C 7 H 6 O 3
分子量：	167.12
蒸发速率：
粘性：
溶解性：	溶于水，易溶于乙醇、乙醚、氯仿。
主要用途：	用作染料中间体、消毒剂、食品防腐剂等。

第十部分：稳定性和反应活性

稳定性：	在常温常压下 稳定
禁配物：	强氧化剂、强碱、潮湿空气。
避免接触的条件：	光照。
聚合危害：	不能出现
分解产物：	一氧化碳、二氧化碳。

第十一部分：毒理学资料

急性毒性：	LD50：891mg／kg(大鼠经口)
急性中毒：
慢性中毒：
亚急性和慢性毒性：
刺激性：
致敏性：
致突变性：
致畸性：
致癌性：

第十二部分：生态学资料

生态毒理毒性：
生物降解性：
非生物降解性：
生物富集或生物积累性：

第十三部分：废弃处置

废弃物性质：
废弃处置方法：	处置前应参阅国家和地方有关法规。建议用焚烧法处置。
废弃注意事项：

第十四部分：运输信息

危险货物编号：
UN编号：
包装标志：
包装类别：
包装方法：
运输注意事项：	储存于阴凉、通风仓间内。远离火种、热源。防止阳光直射。保持容器密封。应与氧化剂、碱类分开存放。搬运时要轻装轻卸，防止包装及容器损坏。起运时包装要完整，装载应稳妥。运输过程中要确保容器不泄漏、不倒塌、不坠落、不损坏。严禁与氧化剂、碱类、食用化学品等混装混运。运输途中应防曝晒、雨淋，防高温。车辆运输完毕应进行彻底清扫。
RETCS号：
IMDG规则页码：

第十五部分：法规信息

国内化学品安全管理法规：	化学危险物品安全管理条例 (1987年2月17日国务院发布)，化学危险物品安全管理条例实施细则 (化劳发[1992] 677号)，工作场所安全使用化学品规定 ([1996]劳部发423号)等法规，针对化学危险品的安全使用、生产、储存、运输、装卸等方面均作了相应规定。
国际化学品安全管理法规：

第十六部分：其他信息

参考文献：	1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
填表时间：	年月日
填表部门：
数据审核单位：
修改说明：
其他信息：	4
MSDS修改日期：	年月日

制备方法与用途

根据提供的信息,我可以总结并提供以下关于水杨酸的要点:

1. 化学性质:

• 白色针状结晶或单斜棱晶
• 有辛辣味
• 微溶于水,易溶于有机溶剂

2. 主要用途:

• 医药工业:生产阿司匹林、利尿药物等
• 染料工业:生产各种染料
• 香料工业:用作香精原料
• 农药工业:生产杀虫剂中间体
• 橡胶工业:用作防焦剂等

3. 生产方法: 由苯酚钠盐与二氧化碳反应,再经酸化制得。

4. 安全性注意事项: 具有一定的腐蚀性和刺激性,使用时应注意防护。 可引起过敏或刺激皮肤、眼睛。吸入粉尘会引起呼吸道刺激。

5. 食品添加剂方面: 作为食品香料使用,但需符合最大允许使用量标准。

6. 用途广泛,涉及医药、染料、农药等多个领域,是重要的有机合成原料之一。

希望这些信息对您有帮助!如果您需要更详细的信息或有其他问题,请随时告知。

反应信息

• 作为反应物：
  描述：

  水杨酸 在 N-甲基吡咯烷酮 、 盐酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 7.0h， 生成 3-烯丙基-2-羟基苯甲酸甲酯
  参考文献：
  名称：

  Zatosetron，一种有效，选择性和长效的5HT3受体拮抗剂：合成与结构活性关系。

  摘要：

  5HT3受体拮抗剂在临床上可有效治疗与某些溶瘤药物（包括顺铂）相关的恶心和呕吐。此外，这些药物可用于几种中枢神经系统疾病的药理管理，包括焦虑症，精神分裂症，痴呆症和药物滥用。我们对芳酰基环戊酰胺的研究导致发现二氢苯并呋喃基酯和酰胺是有效的5HT3受体拮抗剂。通过对麻醉大鼠静脉注射5-羟色胺（5HT）产生的心动过缓的阻滞判断，Tropine和3α-aminotropane的简单苯甲酰基衍生物具有较弱的5HT3受体拮抗剂活性。在这个系列中，使用苯并呋喃-7-羧酰胺作为芳酰基部分导致5HT3受体亲和力的显着提高。通过广泛的SAR研究确定的最佳5HT3受体拮抗剂是5-氯-2,3-二氢-2,2-二甲基-N-（8-甲基-8-氮杂双环[3.2.1] oc t-3-yl ）-7-苯并呋喃甲酰胺（Z）-2-butenedioate（马来酸zatosetron）。7-氨基甲酰基区域化学，二甲基取代，氯取代基和

  DOI：

  10.1021/jm00080a016
• 作为产物：
  描述：

  水杨基羟肟酸 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 水杨酸
  参考文献：
  名称：

  Ghosh, Kallol K.; Ghosh, Sharmistha; Thakur, Santosh S., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1996, vol. 35, # 2, p. 121 - 126

  摘要：

  DOI：
• 作为试剂：
  描述：

  N,N-dimethyl-4-ethylaniline 在 氟硼酸钠 、 氧气 、 水杨酸 、 copper(l) chloride 作用下， 以 乙腈 为溶剂， 反应 15.0h， 以60%的产率得到4-ethyl-N-methylphenylformamide
  参考文献：
  名称：

  一种合成N-芳基甲酰胺类化合物的方法

  摘要：

  一种合成N‑芳基甲酰胺类化合物的方法，其步骤为N,N‑二甲基苯胺化合物、氯化亚铜、四氟硼酸钠盐和水杨酸在氧气气氛下，放入有机溶剂中，所述的有机溶剂的用量为：N,N‑二甲基苯胺化合物、氯化亚铜、四氟硼酸钠盐和水杨酸的物质的量浓度为0.5～1mol/L，30～60℃下反应0.5～48小时，分离纯化产物，得到N‑芳基甲酰胺类化合物；本发明具有操作简单，所用催化剂廉价，反应条件温和，产物收率高，克服了传统的原料试剂昂贵、条件苛刻、合成步骤冗长、总收率不高等不足，具有很好的应用前景的优点。

  公开号：

  CN108752155A

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-OCF3、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、-CF3、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、-CF3、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• [EN] SULFINYLPYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] SULFINYLPYRIDINES ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：OBLIQUE THERAPEUTICS AB

  公开号：WO2018146468A1

  公开（公告）日：2018-08-16

  There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3, R4 and n have meanings provided in the description, which compounds are useful in the treatment of cancers.

  提供了式I（I）的化合物或其药用盐，其中L、R1、R2、R3、R4和n的含义如描述中所提供，这些化合物在治疗癌症方面是有用的。
• Additives and products including oligoesters
  申请人：——

  公开号：US20030199593A1

  公开（公告）日：2003-10-23

  The present invention relates to oligoesters and their use or the creation of additives. Oligoester containing additives and/or oligoesters themselves may be used for formulating pharmaceutical preparations, cosmetics or personal care products such as shampoos and conditioners. These oligoesters are particularly useful for the creation of multi-purpose additives that can impart conditioning, long substantivity and/or UV protection. Individual oligoesters and oligoester mixtures are described.

  本发明涉及寡酯及其用途或添加剂的制备。含有寡酯的添加剂和/或寡酯本身可用于配制药物制剂、化妆品或个人护理产品，如洗发水和护发素。这些寡酯对于制备能够赋予调理、长效性和/或紫外线保护的多功能添加剂特别有用。描述了单独的寡酯和寡酯混合物。
• Novel processes for the preparation of adenosine compounds and intermediates thereto
  申请人：——

  公开号：US20030069423A1

  公开（公告）日：2003-04-10

  Novel processes for the preparation of adenosine compounds and intermediates thereto. The adenosine compounds prepared by the present processes may be useful as cardiovascular agents, more particularly as antihypertensive and anti-ischemic agents, as cardioprotective agents which ameliorate ischemic injury or myocardial infarct size consequent to myocardial ischemia, and as an antilipolytic agents which reduce plasma lipid levels, serum triglyceride levels, and plasma cholesterol levels. The present processes may offer improved yields, purity, ease of preparation and/or isolation of intermediates and final product, and more industrially useful reaction conditions and workability.

  新型的制备腺苷化合物及其中间体的方法。通过本方法制备的腺苷化合物可能作为心血管药物有用，更具体地作为降压和抗缺血药物，作为改善缺血性损伤或心肌梗死大小的心脏保护剂，以及作为降脂剂，可降低血浆脂质水平、血清甘油三酯水平和血浆胆固醇水平。本方法可能提供改善产率、纯度、制备和/或中间体和最终产品的分离的便利性，以及更具工业应用的反应条件和可操作性。

表征谱图