丙酰马嗪 | 362-29-8

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 丙酰马嗪
• 中文别名: 丙酰异丙嗪
• 英文名称: propiomazine
• 英文别名: Propiomazin；1-[10-[2-(dimethylamino)propyl]phenothiazin-2-yl]propan-1-one
• CAS: 362-29-8
• 化学式: C₂₀H₂₄N₂OS
• 分子量: 340.489
• InChiKey: UVOIBTBFPOZKGP-UHFFFAOYSA-N

物化性质

• 沸点：
  bp0.5 235-245°
• 密度：
  1.137±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 溶解度：
  0.454 mg/L
• 保留指数：
  2736;2740;2738;2738;2720;2740;2738;2759.3

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  48.8
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

未知，但与其他吩噻嗪类药物一样，最可能是肝脏的。

Unknown, but most likely hepatic as with other phenothiazines.

来源:DrugBank

代谢

未知，但与其他吩噻嗪类药物一样，最可能是肝脏的。

Unknown, but most likely hepatic as with other phenothiazines.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

丙嗪是一种针对1型、2型和4型多巴胺受体、5-羟色胺（5-HT）2A型和2C型受体、毒蕈碱型受体1至5、α(1)受体和组胺H1受体的拮抗剂。其主要作为镇静剂使用是由于其抗组胺效果。

Propiomazine is an antagonist at types 1, 2, and 4 dopamine receptors, serotonin (5-HT) receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Its main use as a sedative is due to its antihistamine effect.

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

它们会导致言语不清、定向障碍和“醉酒”行为。它们在身体和心理上都会产生依赖。

They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

罕见的严重副作用包括抽搐（癫痫发作）；呼吸困难或呼吸异常加快；心跳或脉搏过快或不规则；高烧；高血压或低血压；尿失禁；肌肉僵硬（严重）；异常大量出汗；皮肤异常苍白；以及异常的疲劳或虚弱。

Rare, serious side effects include convulsions (seizures); difficult or unusually fast breathing; fast or irregular heartbeat or pulse; fever (high); high or low blood pressure; loss of bladder control; muscle stiffness (severe); unusual increase in sweating; unusually pale skin; and unusual tiredness or weakness.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

增强中枢神经系统抑制剂的效果：因此，同时给予巴比妥类药物的剂量应减少1/2，美沙酮和吗啡的剂量应减少1/4至1/2。/氢氯酸盐/

...ENHANCES EFFECT OF CNS DEPRESSANTS: HENCE, DOSE OF BARBITURATES GIVEN CONCOMITANTLY SHOULD BE REDUCED 1/2, DOSES OF MEPERIDINE & MORPHINE SHOULD BE REDUCED 1/4 TO 1/2. /HYDROCHLORIDE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约一半的常用吩噻嗪类药物的代谢物在尿液中找到，其余在粪便中。吩噻嗪类药物在体内的最终停留时间非常长。停药6个月后，尿液中仍可检测到各种代谢物。/吩噻嗪类药物/

APPROX HALF OF METABOLITES OF COMMONLY USED PHENOTHIAZINES ARE FOUND IN URINE & REST IN FECES. ULTIMATE SOJOURN OF PHENOTHIAZINE DRUGS IN BODY IS EXCEEDINGLY LONG. 6 MO AFTER DISCONTINUATION OF THESE DRUGS, VARIOUS METABOLITES ARE DETECTABLE IN URINE. /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吩噻嗪类镇静剂迅速穿过胎盘，多年来人们已经在接受治疗的母亲的尿液和新生儿组织中测量到它们，但直到最近才测量到母亲和胎儿体内的血药浓度非常低... /吩噻嗪类/

PHENOTHIAZINE TRANQUILIZERS CROSS PLACENTA RAPIDLY, & THEY HAVE BEEN MEASURED FOR MANY YR IN URINE & TISSUES OF NEONATES OF TREATED MOTHERS, BUT VERY LOW BLOOD LEVELS OF MOTHERS & FETUSES HAVE BEEN MEASURED ONLY RECENTLY... /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

丙酰马嗪属于吩噻嗪类抗组胺药，主要用于麻醉前和手术中以达到镇静和止吐的效果。

反应信息

• 作为反应物：
  描述：

  丙酰马嗪 在 mercury dichloride 、 锌 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 15.0h， 生成 dimethyl-[1-methyl-2-(2-trans-propenyl-phenothiazin-10-yl)-ethyl]-amine
  参考文献：
  名称：

  Schmitt,J. et al., Bulletin de la Societe Chimique de France, 1961, p. 341 - 349

  摘要：

  DOI：
• 作为产物：
  描述：

  10H-​Phenothiazine-​10-​carbonyl chloride, 2-​(1-​oxopropyl)​- 、 alkaline earth salt of/the/ methylsulfuric acid 生成 丙酰马嗪
  参考文献：
  名称：

  Schmitt et al., Bulletin de la Societe Chimique de France, 1957, p. 1474,1480

  摘要：

  DOI：

文献信息

• Internally Masked Neopentyl Sulfonyl Ester Cyclization Release Prodrugs of Acamprosate, Compositions Thereof, and Methods of Use
  申请人：Li Yunxiao

  公开号：US20090099253A1

  公开（公告）日：2009-04-16

  Internally masked neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

  内部掩盖的新戊基磺酰酯前药，包含这种前药的药物组合物，以及使用这种前药和组合物治疗疾病的方法被披露。具体来说，披露了展现增强口服生物利用度的阿卡姆普罗酸前药以及使用阿卡姆普罗酸前药治疗神经退行性疾病、精神障碍、情绪障碍、焦虑障碍、躯体形式障碍、运动障碍、物质滥用障碍、暴饮暴食障碍、皮层扩散性抑郁相关障碍、耳鸣、睡眠障碍、多发性硬化症和疼痛的方法。
• [EN] COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS<br/>[FR] COMPOSITIONS ET PROCÉDÉS PERMETTANT D'ADMINISTRER DES AGENTS THÉRAPEUTIQUES
  申请人：MODERNATX INC

  公开号：WO2017099823A1

  公开（公告）日：2017-06-15

  This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

  这项披露提供了改进的基于脂质的组合物，包括脂质纳米粒子组合物，以及它们用于体内传递药剂的方法，包括核酸和蛋白质。这些组合物不受加速血清清除的影响，并且它们在体内具有改进的毒性特性。
• [EN] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143143A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• MASKED CARBOXYLATE NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE
  申请人：Jandeleit Bernd

  公开号：US20090069419A1

  公开（公告）日：2009-03-12

  Masked carboxylate neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

  掩蔽羧酸新戊磺酰酯丙戊酸酯前药，包含此类前药的药物组合物，以及使用此类前药和组合物治疗疾病的方法被披露。具体来说，披露了表现出增强口服生物利用度的丙戊酸酯前药和使用丙戊酸酯前药治疗神经退行性疾病、精神疾病、情绪障碍、焦虑障碍、躯体形式障碍、运动障碍、物质滥用障碍、暴饮暴食障碍、皮层扩散性抑郁相关障碍、耳鸣、睡眠障碍、多发性硬化症和疼痛的方法。

表征谱图