onchidal | 67656-42-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: onchidal
• 英文别名: [(1E,3E)-5-(2,2-dimethyl-6-methylidenecyclohexyl)-3-formylpenta-1,3-dienyl] acetate
• CAS: 67656-42-2
• 化学式: C₁₇H₂₄O₃
• 分子量: 276.376
• InChiKey: BEKQPDFPPJFVJP-AHSQCEKMSA-N

物化性质

• 沸点：
  371.5±25.0 °C(Predicted)
• 密度：
  1.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

对氧磷酶（PON1）是有机磷代谢的关键酶。PON1可以通过水解使一些有机磷失活。PON1水解多种有机磷杀虫剂以及神经毒剂（如梭曼、沙林和VX）的活性代谢物。PON1的多态性导致不同个体之间酶水平和催化效率的差异，这反过来表明不同个体可能更容易受到有机磷暴露的毒性影响。

Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Onchidal是一种胆碱酯酶或乙酰胆碱酯酶（AChE）抑制剂。胆碱酯酶抑制剂（或“抗胆碱酯酶”）抑制乙酰胆碱酯酶的作用。由于其基本功能，干扰乙酰胆碱酯酶作用的化学物质是强大的神经毒素，低剂量时会导致过度流涎和眼泪，随后是肌肉痉挛，最终导致死亡。神经气体和许多用于杀虫剂的物质已被证明通过结合乙酰胆碱酯酶活性位点的丝氨酸，完全抑制该酶。乙酰胆碱酯酶分解神经递质乙酰胆碱，该递质在神经和肌肉接头处释放，以使肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积聚并继续发挥作用，使得任何神经冲动不断传递，肌肉收缩不会停止。最常见的乙酰胆碱酯酶抑制剂之一是基于磷的化合物，它们被设计用来结合到酶的活性位点上。结构要求是一个带有两个亲脂性基团的磷原子，一个离去基团（如卤素或硫氰酸盐），以及一个末端的氧。

Onchidal is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

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

急性接触胆碱酯酶抑制剂可能会导致胆碱能危象，表现为严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、晕厥和抽搐。肌肉无力可能性增加，如果呼吸肌受累，可能会导致死亡。在运动神经积累的乙酰胆碱会导致神经肌肉接头处烟碱受体的过度刺激。当这种情况发生时，可能会看到肌肉无力、疲劳、肌肉痉挛、肌束震颤和麻痹的症状。当自主神经节积累乙酰胆碱时，这会导致交感系统中烟碱受体的过度刺激。与此相关的症状是高血压和低血糖。由于乙酰胆碱积累而在中枢神经系统中过度刺激烟碱乙酰胆碱受体，会导致焦虑、头痛、抽搐、共济失调、呼吸和循环抑制、震颤、全身无力，甚至可能昏迷。当由于副交感乙酰胆碱受体上乙酰胆碱过多而导致毒蕈碱过度刺激时，可能会出现视力障碍、胸部紧绷、由于支气管收缩引起的喘息、支气管分泌物增加、唾液分泌增加、流泪、出汗、肠蠕动和排尿的症状。对于男性和女性的生育、生长和发育，已经特别将与有机磷农药暴露联系起来。关于生殖影响的大多数研究都是在农村地区使用杀虫剂和杀虫剂的农民进行的。在女性中，月经周期紊乱、怀孕时间延长、自然流产、死产以及后代的一些发育效应与有机磷农药暴露有关。产前暴露与胎儿生长和发育受损有关。神经毒性效应也与人因接触有机磷农药而中毒引起的四种神经毒性效应有关：胆碱能综合症、中间综合症、有机磷诱导的迟发性多发性神经病（OPIDP）和慢性有机磷诱导的神经精神障碍（COPIND）。这些综合症在急性接触和慢性接触有机磷农药后出现。

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

注射（刺伤/咬伤）(L1815)

Injection (sting/bite) (L1815)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

Shellfish poisoning may cause numbness and tingling of the lips, tongue, face, and extremities, followed nausea and vomiting. Convulsions and progression to respiratory paralysis may occur. (A594) 贝类中毒可能会引起嘴唇、舌头、面部和四肢的麻木和刺痛，随后出现恶心和呕吐。可能会发生抽搐，并进展到呼吸麻痹。 (A594)

Shellfish poisoning may cause numbness and tingling of the lips, tongue, face, and extremities, followed nausea and vomiting. Convulsions and progression to respiratory paraylsis may occur. (A594)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  onchidal 、 1-氨基戊烷 以 氘代氯仿 为溶剂， 以56%的产率得到N-(2-(2,2-dimethyl-6-methylenecyclohexyl)-1-(1-pentyl-1H-pyrrol-3-yl)ethyl)pentan-1-amine
  参考文献：
  名称：

  研究具有生物活性的海洋倍半萜类杀昆虫剂和模型化合物的亲电反应性。

  摘要：

  无壳软体动物Onchidella binneyi防御分泌成分的倍半萜烯ondaldal（6）的结构包含被掩盖的α，β-不饱和1,4-二醛部分，有人提出将其存在。软体动物表现出进食威慑作用的原因。我们已经发现杀螨剂可作为亲电子试剂，与模型亲核试剂n-戊胺快速反应，形成非对映体胺化的吡咯加合物。令人惊讶的是，未发现在杀昆虫剂和正戊硫醇之间发生反应。制备了结构简化的onchidal的正戊基11-13和环己基甲基15-17类似物，并证明了相似的胺选择性反应性。杀昆虫剂和类似物与模型蛋白溶菌酶反应，形成共价加合物，并导致蛋白交联。

  DOI：

  10.3762/bjoc.14.197

文献信息

• TWO-PHASE FERMENTATION PROCESS FOR THE PRODUCTION OF AN ORGANIC COMPOUND
  申请人：JANSSEN Antonius Cornelis Johannes Matheus

  公开号：US20160168595A1

  公开（公告）日：2016-06-16

  The invention relates to a two phase fermentation process for producing an organic compound, in particular an isoprenoid and to a bioreactor comprising a two phase fermentation system for producing an organic compound.

  本发明涉及一种用于生产有机化合物的两相发酵过程，特别是一种异戊二烯类化合物的生产方法，以及一种包括两相发酵系统的生物反应器，用于生产有机化合物。
• DRUG SUITABILITY ASSESSMENT METHOD FOR PREVENTION OR TREATMENT OF ANXIETY DISORDERS USING CHOLINERGIC TYPE II THETA RHYTHM
  申请人：Korea Institute of Science and Technology

  公开号：EP2428209A1

  公开（公告）日：2012-03-14

  The present invention relates to a drug suitability assessment method for the prevention or treatment of anxiety disorders using the cholinergic type II theta rhythm, and, more specifically, to a method for detecting individuals suffering from anxiety disorders induced by an abnormality occurring in the cholinergic system using the type II theta rhythm profile which is based on findings that the cholinergic type II theta rhythm is lower in an animal anxiety model than in normal subjects and that cholinergic drug treatment induces the cholinergic type II theta rhythm to return to normal and reduces anxiety and thereby making it possible to determine if a subject can be appropriately administered with a cholinergic drug and to monitor progress after cholinergic drug treatment.

  本发明涉及一种利用胆碱能II型θ节律预防或治疗焦虑症的药物适用性评估方法，更具体地说，涉及一种利用胆碱能II型θ节律特征检测焦虑症患者的方法、本发明涉及一种利用胆碱能Ⅱ型θ节律谱检测因胆碱能系统发生异常而诱发的焦虑症患者的方法，该方法基于以下发现：在动物焦虑模型中，胆碱能Ⅱ型θ节律低于正常受试者，而胆碱能药物治疗可诱导胆碱能Ⅱ型θ节律恢复正常并减轻焦虑，从而可以确定受试者是否可以适当使用胆碱能药物，并监测胆碱能药物治疗后的进展情况。
• Use of anti-connexin agents for enhancing the therapeutic effect of acetylcholinesterase inhibitor
  申请人：Commissariat à l'Énergie Atomique et aux Énergies Alternatives

  公开号：EP2586436A1

  公开（公告）日：2013-05-01

  This invention relates to improvements in therapeutic neurological and neuropsychic treatments using acetylcholinesterase inhibitors. More specifically, the invention enables the effects of the reversible acetylcholinesterase inhibitor donepezil to be potentiated by certain molecules, referred to here as connexin-blocking agents. Said connexin-blocking agent is preferably meclofenamic acid.

  本发明涉及使用乙酰胆碱酯酶抑制剂对神经和神经心理治疗的改进。更具体地说，本发明使可逆性乙酰胆碱酯酶抑制剂多奈哌齐的作用能够通过某些分子（在此称为连接蛋白阻断剂）得到增强。所述附着素阻断剂最好是甲氯芬那酸。
• Method and compositions for solubilizing non-polar constituents
  申请人：Entourage Bioscience, LLC

  公开号：US10376586B2

  公开（公告）日：2019-08-13

  A method for solubilizing non-polar target compounds into a carrier liquid is described. A carrier oil, such as a MCT, or a mixture of MCTs, may be used to solubilize non-polar target compounds. The carrier oil may also include one or more buffers for stability of the target compounds within the carrier oil.

  本文介绍了一种将非极性目标化合物溶解到载液中的方法。载体油，如 MCT 或 MCT 混合物，可用于增溶非极性目标化合物。载体油还可包括一种或多种缓冲剂，以保证目标化合物在载体油中的稳定性。
• Acetylcholinesterase inhibitors for treatment of dermatological conditions
  申请人：Attillaps Holdings

  公开号：US10500183B2

  公开（公告）日：2019-12-10

  Embodiments of the invention involve treating skin afflictions by the topical or oral use of acetylcholinesterase inhibitor. By effectively reducing or eliminating the population of Demodex mites in affected skin areas and areas where Demodex mites may exist, this treatment achieves a more complete remission of clinical signs and symptoms of the skin afflictions than any previously described method. Embodiments of the invention are useful for treating skin afflictions including common acne, seborrheic dermatitis, perioral dermatitis, an acneform rash, transient acantholytic dermatosis, acne necrotica milliaris, psoriasis, steroid induced dermatitis, primary irritation dermatitis and rosacea.

  本发明的实施方案涉及通过局部或口服乙酰胆碱酯酶抑制剂来治疗皮肤病。通过有效减少或消除受影响皮肤区域和可能存在德氏螨的区域的德氏螨种群，这种治疗方法比以前描述的任何方法都能更彻底地缓解皮肤病的临床症状和体征。本发明的实施方案可用于治疗皮肤病，包括常见的痤疮、脂溢性皮炎、口周皮炎、痤疮皮疹、一过性棘皮溶解性皮肤病、千金痤疮、银屑病、类固醇诱发性皮炎、原发性刺激性皮炎和酒渣鼻。