氯普鲁卡因 | 133-16-4

• 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: 氯普鲁卡因
• 中文别名: 纳塞卡因；2-二乙氨基-4-氨基-2-氯苯甲酸乙酯
• 英文名称: chloroprocaine
• 英文别名: 4-amino-2-chloro-benzoic acid-β-diethylaminoethyl ester；Chloroprocain；Chlorprocain；4-amino-2-chloro-benzoic acid-(2-diethylamino-ethyl ester)；4-Amino-2-chlor-benzoesaeure-(2-diaethylamino-aethylester)；2-(diethylamino)ethyl 4-amino-2-chlorobenzoate
• CAS: 133-16-4
• 化学式: C₁₃H₁₉ClN₂O₂
• mdl: MFCD00864416
• 分子量: 270.759
• InChiKey: VDANGULDQQJODZ-UHFFFAOYSA-N

物化性质

• 熔点：
  42°C
• 沸点：
  402.6±35.0 °C(Predicted)
• 密度：
  1.2020 (rough estimate)
• 物理描述：
  Solid
• 气味：
  ODORLESS
• 溶解度：
  0.665 mg/mL
• 稳定性/保质期：
  STABLE IN AIR /HYDROCHLORIDE/
• 分解：
  When heated to decomposition it emits toxic fumes of nitroxides and /hydrogen chloride/.
• 保留指数：
  2229;2229

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

在血浆中，氯普鲁卡因迅速被拟胆碱酯酶代谢，这是一组执行酯键水解的酶。在眼组织内，氯普鲁卡因被非特异性酯酶代谢。氯普鲁卡因的水解导致产生ß-二乙氨基乙醇和2-氯-4-氨基苯甲酸，后者抑制磺胺类药物的作用。

In plasma, chloroprocaine is quickly metabolized by pseudocholinesterases, a group of enzymes that perform the hydrolysis of the ester linkage. In ocular tissues, chloroprocaine is metabolized by nonspecific esterases. The hydrolysis of chloroprocaine leads to the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid, which inhibits the action of the sulfonamides.

来源:DrugBank

代谢

2-二乙氨基乙基 4-氨基-2-氯苯甲酸盐在大鼠体内转化为 4-氨基-2-氯苯甲酸。Livett, BH & RM Lee, 生物化学药物 17, 385 (1968)。/来自表格/

2-DIETHYLAMINOETHYL 4-AMINO-2-CHLOROBENZOATE YIELDS 4-AMINO-2-CHLOROBENZOIC ACID IN GUINEA PIGS. LIVETT, BH & RM LEE, BIOCHEM PHARMAC 17, 385 (1968). /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

经血浆胆碱酯酶主要水解，肝脏酯酶也可水解/生成二乙氨基乙醇和2-氯-4-氨基苯甲酸/人体，静脉注射。动物研究表明，某些局部麻醉药可能经历胆汁回收/ /氯普鲁卡因 HCL/

HYDROLYZED /CHIEFLY/ BY PLASMA PSEUDOCHOLINESTERASES /& ALSO BY ESTERASES IN LIVER/ AS DIETHYLAMINOETHANOL & 2-CHLORO-4-AMINOBENZOIC ACID /HUMAN, PARENTERAL. ANIMAL STUDIES SUGGEST THAT SOME LOCAL ANESTHETICS MAY UNDERGO BILIARY RECYCLING/ /CHLOROPROCAINE HCL/

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯普鲁卡因在血浆中通过拟胆碱酯酶水解酯键而迅速代谢。 消除途径：氯普鲁卡因在血浆中通过拟胆碱酯酶水解酯键而迅速代谢。尿液排泄受尿液灌注和影响尿液pH的因素影响。 半衰期：21 +/- 2秒

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. Route of Elimination: Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH. Half Life: 21 +/- 2 seconds

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

氯普鲁卡因主要通过抑制外周神经神经元细胞膜上的电压门控钠通道的钠离子流入发挥作用。当钠离子的流入被中断时，无法产生动作电位，从而抑制信号传导。受体位点被认为位于钠通道的细胞质（内侧）部分。有人假设氯普鲁卡因能结合或拮抗N-甲基-D-天门冬氨酸（NMDA）受体以及尼古丁型乙酰胆碱受体和血清素受体-离子通道复合物。

Chloroprocaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. It is hypothesized that Chloroprocaine binds or antagonizes the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

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

中枢神经系统影响：这些表现为兴奋和/或抑制。可能出现不安、焦虑、眩晕、耳鸣、视力模糊或震颤，可能会进一步发展为抽搐。高剂量，或意外血管内注射，可能导致高血浆水平及相关的心肌抑制、低血压、心动过缓、室性心律失常，甚至可能心脏骤停。神经病学副作用 这些观察可能包括不同程度（包括完全性）的脊髓阻滞，脊髓阻滞引起的低血压，以及膀胱和大便控制丧失，会阴部感觉和性功能丧失。蛛网膜炎、持续的运动、感觉和/或自主（括约肌控制）一些下脊髓段的缺陷，缓慢恢复（几个月）或不完全恢复在罕见情况下有报道。[维基百科]

Central Nervous System Effects: These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision or tremors may occur, possibly proceeding to convulsions. High doses, or unintended intravascular injection, may lead to high plasma levels and related depression of the myocardium, hypotension, bradycardia, ventricular arrhythmias and, possibly, cardiac arrest. Neurologic side effects These observations may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. Arachnoiditis, persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances. [Wikipedia]

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：目前没有关于在母乳喂养期间使用氯普鲁卡因的信息。基于其他局部麻醉药进入母乳的排泄量较低，以及氯普鲁卡因的半衰期极短，它不太可能对哺乳婴儿产生不利影响。然而，尤其是当哺乳新生儿或早产儿时，可能更倾向于使用替代药物。 ◉ 对哺乳婴儿的影响：截至修订日期，未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，未找到相关的已发布信息。

◉ Summary of Use during Lactation:No information is available on the use of chloroprocaine during breastfeeding. Based on the low excretion of other local anesthetics into breastmilk and the extremely short half-life of chloroprocaine, it is unlikely to adversely affect the breastfed infant. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ 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)

毒理性

• 暴露途径

静脉注射。局部麻醉药的全身吸收速率取决于给药的总剂量和药物浓度、给药途径、给药部位的血管丰富程度，以及麻醉注射中是否含有肾上腺素。

Parenteral (intravenous injection). The rate of systemic absorption of local anesthetic drugs is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic injection.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

由于其系统毒性风险低，氯普鲁卡因的作用迅速，通常在6到12分钟内生效。氯普鲁卡因引起的麻醉持续时间可达60分钟。局部麻醉药的吸收率取决于氯普鲁卡因的总剂量和浓度，以及给药途径、给药部位的血管丰富程度，以及麻醉注射中是否含有肾上腺素。肾上腺素的存在会降低局部麻醉药的吸收率和血浆浓度。尚未评估氯普鲁卡因局部眼部给药后的系统暴露情况。

Thanks to its low risk for systemic toxicity, chloroprocaine has a rapid onset of action that usually ranges between 6 to 12 minutes. The duration of chloroprocaine-induced anesthesia may be up to 60 minutes. The absorption rate of local anesthetics depends on the total dose and concentration of chloroprocaine, as well as the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic injection. The presence of epinephrine reduces the rate of absorption and plasma concentration of local anesthetics. The systemic exposure to chloroprocaine following its topical ocular administration has not been evaluated.

来源:DrugBank

吸收、分配和排泄

• 消除途径

像大多数局部麻醉药及其代谢物一样，氯普鲁卡因主要通过肾脏排泄。氯普鲁卡因的尿排泄可能受到尿流量以及影响尿pH的因素的影响。

Like most local anesthetics and their metabolites, chloroprocaine is mainly excreted by the kidneys. The urinary excretion of chloroprocaine may be affected by urinary perfusion and factors that have an effect on urinary pH.

来源:DrugBank

吸收、分配和排泄

盐酸普鲁卡因经肌内注射后可被迅速吸收...不会长时间停留在注射部位。...吸收后，盐酸普鲁卡因可被迅速水解.../盐酸普鲁卡因/

PROCAINE IS READILY ABSORBED FOLLOWING PARENTERAL ADMIN ... DOES NOT LONG REMAIN @ SITE OF INJECTION. ... FOLLOWING ABSORPTION, PROCAINE IS RAPIDLY HYDROLYZED ... /PROCAINE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

麻醉剂与血清中的蛋白质以及组织的结合减少了全身循环中游离药物的浓度，从而降低了毒性。/酯类局部麻醉剂/主要通过血浆酯酶（可能是血浆胆碱酯酶）水解和灭活。肝脏也参与局部麻醉剂的水解。/局部麻醉剂/

... Binding of the anesthetic to proteins in the serum and to tissues reduces the concentration of free drug in the systemic circulation and, consequently, reduces toxicity. ... /Ester local anesthetics/ are hydrolyzed and inactivated primarily by a plasma esterase, probably plasma cholinesterase. The liver also participates in hydrolysis of local anesthetics. /Local anesthetics/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氯普鲁卡因的系统毒性小于所有其他局部麻醉药，这是因为它能被血浆胆碱酯酶快速水解，从而缩短其在血浆中的半衰期。

THE SYSTEMIC TOXICITY OF CHLOROPROCAINE IS LESS THAN THAT OF ALL OTHER LOCAL ANESTHETICS BECAUSE OF ITS RAPID HYDROLYSIS BY PLASMA CHOLINESTERASE ... WHICH SHORTENS THE PLASMA HALF-LIFE.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2922499990
• 储存条件：
  存储条件：2-8°C，密封，避光，惰性气体

制备方法与用途

氯普鲁卡因（2-氯普鲁卡因）是一种有效的钠钾-ATP酶活性抑制剂，其半数有效浓度为13毫摩尔/升。该物质能够阻断周围神经。

反应信息

• 作为反应物：
  描述：

  氯普鲁卡因 、 2-二乙氨基氯乙烷盐酸盐 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 10.0h， 以36.5%的产率得到2-chloro-4-{[2-(diethylamino)ethyl]amino}benzoic acid-2-(diethylamino)ethyl ester
  参考文献：
  名称：

  一种微波促进合成氯普鲁卡因杂质的方法

  摘要：

  本发明属于医药领域，主要涉及一种盐酸氯普鲁卡因杂质2‑氯‑4‑{[2‑(二乙基氨基)乙基]氨基}苯甲酸‑2‑(二乙基氨基)乙基酯(式I)的合成方法，本发明以氯普鲁卡因为原料，溶解在偶极溶剂中，与2‑二乙胺基氯乙烷盐酸盐在无机碱存在下，微波条件下反应得到目标杂质。本发明具有反应时间短，合成操作简便，易于纯化操作，收率高，纯度高等特点，可作为盐酸氯普鲁卡因质量控制的必需品或应用于盐酸氯普鲁卡因杂质对照品研究。

  公开号：

  CN114702404A
• 作为产物：
  描述：

  2-(diethylamino)ethyl 2-chloro-4-nitrobenzoate 在 水 、 铂 作用下， 生成 氯普鲁卡因
  参考文献：
  名称：

  DE937232

  摘要：

  公开号：

文献信息

• AKT INACTIVATION BY TOCOPHERYL DERIVATIVES
  申请人：Chen Ching-Shih

  公开号：US20140031388A1

  公开（公告）日：2014-01-30

  Anticancer compounds according to formula I are described herein. wherein R 1 , R 2 , R 3 and R 4 are selected from H, CH 3 , OH, SH, OCH 3 , NHR′, halogen, CF 3 , N-linked pyrrolidine, and SO 2 NHR′, or any combination thereof; R 5 is an alkyl, alkenyl, or alkaryl group including from 4 to 11 carbons, X is selected from CH 2 , CHOH, C═O, S═O, O═S═O, and an oxetane ring, Y is selected from CH 2 , O, and NH, and R′ is a H, aryl, or a lower alkyl group, or pharmaceutically acceptable salts thereof. The compounds have been shown to facilitate site-specific dephosphorylation of Akt at Ser-473, thereby inactivating Akt and decreasing dysregulation of Akt signaling that can occur in cancer cells.

  根据公式 I，这里描述的抗癌化合物。其中 R1、R2、R3 和 R4 从 H、CH3、OH、SH、OCH3、NHR′、卤素、CF3、N-连接吡咯烷和SO2NHR′ 中选择，或其任意组合；R5 是包括 4 到 11 个碳的烷基、烯基或烷基芳基基团，X 从 CH2、CHOH、C═O、S═O、O═S═O 和氧杂环戒中选择，Y 从 CH2、O 和 NH 中选择，R′ 是 H、芳基或较低烷基基团，或其药用可接受盐。这些化合物已被证明有助于在 Ser-473 处促进 Akt 的位点特异性去磷酸化，从而使 Akt 失活，并减少癌细胞中可能发生的 Akt 信号传导失调。
• [EN] DIHYDROPYRROLONAPHTYRIDINONE COMPOUNDS AS INHIBITORS OF JAK<br/>[FR] COMPOSÉS DE DIHYDROPYRROLONAPHTYRIDINONE COMME INHIBITEURS DE JAK
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010144486A1

  公开（公告）日：2010-12-16

  Disclosed are JAK inhibitors of formula (I) where G1, R1, R2, R3, R4, R5, R6, and R7 are defined in the specification. Also disclosed are pharmaceutical compositions, kits and articles of manufacture which contain the compounds, methods and materials for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other diseases, disorders or conditions associated with JAK.

  揭示了式(I)的JAK抑制剂，其中G1、R1、R2、R3、R4、R5、R6和R7在规范中定义。还披露了含有这些化合物的药物组合物、试剂盒和制造物品，制备这些化合物的方法和材料，以及使用这些化合物治疗涉及免疫系统和炎症的疾病、紊乱和症状的方法，包括类风湿关节炎、血液恶性肿瘤、上皮癌（即癌症）和其他与JAK相关的疾病、紊乱或症状。
• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉASES À CYSTÉINE DE TYPE CATHEPSINES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015054038A1

  公开（公告）日：2015-04-16

  This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及一类新型化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物可用于治疗需要抑制骨吸收的疾病，如骨质疏松症。
• [EN] 2,4-DIAMINOQUINAZOLINES FOR SPINAL MUSCULAR ATROPHY<br/>[FR] 2,4-DIAMINOQUINAZOLINES UTILES POUR LE TRAITEMENT D'UNE ATROPHIE MUSCULAIRE SPINALE
  申请人：DECODE CHEMISTRY INC

  公开号：WO2005123724A1

  公开（公告）日：2005-12-29

  2,4-Diaminoquinazolines of formulae I-IV and VI (I, II, III, IV and VI) are useful for treating spinal muscular atrophy (SMA).

  2,4-二氨基喹唑啉的化学式I-IV和VI（I，II，III，IV和VI）可用于治疗脊髓性肌萎缩症（SMA）。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。

表征谱图