2-Pentenedioic acid, 3-((dimethoxyphosphinyl)oxy)-, dimethyl ester | 122-10-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: 2-Pentenedioic acid, 3-((dimethoxyphosphinyl)oxy)-, dimethyl ester
• 英文别名: dimethyl (Z)-3-dimethoxyphosphoryloxypent-2-enedioate
• CAS: 122-10-1；15272-78-3
• 化学式: C₉H₁₅O₈P
• 分子量: 282.18
• InChiKey: BZSSHIWHSJYWAD-ALCCZGGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  8

ADMET

代谢

在鼠肝酶和谷胱甘肽的存在下，顺式或反式苯基甲基被水解，产生二甲磷酸盐。

IN PRESENCE OF MOUSE LIVER ENZYMES & GLUTATHIONE, CIS- OR TRANS-BOMYL WAS HYDROLYZED WITH PRODUCTION OF DIMETHYL PHOSPHATE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

其他毒药 - 有机磷

Other Poison - Organophosphate

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 解毒与急救

1. 确保气道通畅，如有必要，通过吸痰清除分泌物。如果呼吸抑制，通过机械辅助肺通气给予氧气。在给予阿托品之前尽可能提高组织氧合，以最小化心室颤动的风险。在严重中毒的情况下，可能需要机械支持肺通气数天。2. 给予硫酸阿托品静脉注射，如果静脉注射不可能，则肌内注射。在中度到重度中毒的情况下：成人剂量和12岁以上儿童：每15分钟重复给予0.4-2.0毫克，直到达到阿托品化。用0.02-0.05毫克/千克体重的重复剂量维持阿托品化。/有机磷农药/

1. INSURE THAT A CLEAR AIRWAY EXISTS BY ASPIRATION OF SECRETIONS IF NECESSARY. ADMIN OXYGEN BY MECHANICALLY ASSISTED PULMONARY VENTILATION IF RESPIRATION IS DEPRESSED. IMPROVE TISSUE OXYGENATION AS MUCH AS POSSIBLE BEFORE ADMIN ATROPINE TO MINIMIZE RISK OF VENTRICULAR FIBRILLATION. IN SEVERE POISONINGS, IT MAY BE NECESSARY TO SUPPORT PULMONARY VENTILATION MECHANICALLY FOR SEVERAL DAYS. 2. ADMIN ATROPINE SULFATE IV, OR IM IF IV INJECTION IS NOT POSSIBLE. ... IN MODERATELY SEVERE POISONING: ADULT DOSAGE AND CHILDREN OVER 12 YR: 0.4-2.0 MG REPEATED EVERY 15 MIN UNTIL ATROPINIZATION IS ACHIEVED. MAINTAIN ATROPINIZATION WITH REPEATED DOSAGE OF 0.02-0.05 MG/KG BODY WEIGHT. /ORGANOPHOSPHATE PESTICIDES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

2. 严重中毒的人可能对阿托品表现出显著的耐受性；可能需要两倍或更多倍于上述建议的剂量。可以根据需要增加阿托品的剂量并缩短给药间隔以控制症状。当阿托品需求量很大时，可能需要持续静脉输注阿托品。逆转毒蕈碱样症状和体征，而不是任意剂量限制，是期望的终点。应尽可能使用不含防腐剂的阿托品产品。注意：未中毒或仅轻微有机磷中毒的人可能会因大剂量阿托品出现阿托品中毒的迹象。发热、肌肉颤动和谵妄是阿托品中毒的主要迹象。如果患者在完全阿托品化时出现这些症状，应暂时停止阿托品给药，同时重新评估中毒的严重程度。/有机磷杀虫剂/

2. SEVERELY POISONED INDIVIDUALS MAY EXHIBIT REMARKABLE TOLERANCE TO ATROPINE; TWO OR MORE TIMES THE DOSAGES SUGGESTED ABOVE MAY BE NEEDED. THE DOSE OF ATROPINE MAY BE INCREASED AND THE DOSING INTERVAL DECREASED AS NEEDED TO CONTROL SYMPTOMS. CONTINUOUS INTRAVENOUS INFUSION OF ATROPINE MAY BE NECESSARY WHEN ATROPINE REQUIREMENTS ARE MASSIVE. REVERSAL OF MUSCARINIC SYMPTOMS AND SIGNS, NOT AN ARBITRARY DOSE LIMIT, IS THE DESIRED END-POINT. PRESERVATIVE-FREE ATROPINE PRODUCTS SHOULD BE USED WHENEVER POSSIBLE. NOTE: PERSONS NOT POISONED OR ONLY SLIGHTLY POISONED BY ORGANOPHOSPHATES MAY DEVELOP SIGNS OF ATROPINE TOXICITY FROM SUCH LARGE DOSES. FEVER, MUSCLE FIBRILLATIONS, AND DELIRIUM ARE THE MAIN SIGNS OF ATROPINE TOXICITY. IF THESE APPEAR WHILE THE PATIENT IS FULLY ATROPINIZED, ATROPINE ADMINISTRATION SHOULD BE DISCONTINUED, AT LEAST TEMPORARILY, WHILE THE SEVERITY OF POISONING IS REEVALUATED. /ORGANOPHOSPHATE PESTICIDES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

3. 在给予解磷定之前，抽取（肝素化）血液样本进行胆碱酯酶分析，因为解磷定往往会逆转胆碱酯酶的抑制。4. 在严重中毒情况下给予解磷定（普罗帕米，2-PAM）...在此情况下，呼吸抑制、肌肉无力和抽搐都非常严重。...成人剂量（以及12岁以上的儿童）：静脉注射1.0-2.0克，每分钟不超过0.2克。儿童剂量（12岁以下）：静脉注射20-50毫克/千克（根据严重程度），每分钟注射的总量不超过一半。剂量...如果需要，可以在1-2小时后重复给药，然后每隔10-12小时给药一次。在非常严重的中毒情况下，剂量...可能会加倍。/有机磷农药/

3. DRAW BLOOD SAMPLE (HEPARINIZED) FOR CHOLINESTERASE ANALYSIS BEFORE ADMINISTRATION OF PRALIDOXIME, WHICH TENDS TO REVERSE THE CHOLINESTERASE DEPRESSION. 4. ADMIN PRALIDOXIME (PROTOPAM, 2-PAM) IN CASES OF SEVERE POISONING...IN WHICH RESP DEPRESSION, MUSCLE WEAKNESS & TWITCHINGS ARE SEVERE. ... ADULT DOSAGE AND CHILDREN OVER 12): GIVE 1.0-2.0 G IV @ NO MORE THAN 0.2 G/MIN. CHILD'S DOSE (UNDER 12 YR): GIVE 20-50 MG/KG (DEPENDING ON SEVERITY) IV, INJECTING NO MORE THAN HALF TOTAL DOSE/MIN. DOSAGE...MAY BE REPEATED IN 1-2 HR, THEN @ 10-12 HR INTERVAL IF NEEDED. IN VERY SEVERE POISONINGS, DOSAGE...MAY BE DOUBLED. /ORGANOPHOSPHATE PESTICIDES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

4. 准备好机械辅助呼吸，如果呼吸...减弱...。5. 对于皮肤、衣物、头发和/或眼睛接触有机磷污染的患者，必须在进行复苏和解毒措施的同时进行去污处理，以保护生命。... 6. 如果...摄入的量足以引起中毒，必须清空胃和肠道。A. 通过插管、抽吸和灌洗清空胃，使用等渗盐水中的活性炭悬浮液。必须采取严格措施保护气道，防止反流的物质被吸入。如果受害者昏迷或反应迟钝，在进行胃插管前先插入带套囊的气管内插管。在胃插管和灌洗过程中，保持受害者头部低于胃部水平。...。保持受害者头部向左转。/有机磷杀虫剂/

4. BE PREPD TO ASSIST PULMONARY VENTILATION MECHANICALLY IF RESP ... DEPRESSED ... . 5. IN PATIENTS WHO HAVE BEEN POISONED BY ORGANOPHOSPHATE CONTAMINATION OF SKIN, CLOTHING, HAIR, AND/OR EYES, DECONTAMINATION MUST PROCEED CONCURRENTLY WITH WHATEVER RESUSCITATIVE AND ANTIDOTAL MEASURES ARE NECESSARY TO PRESERVE LIFE. ... 6. IF ... INGESTED IN QUANTITY PROBABLY SUFFICIENT TO CAUSE POISONING, THE STOMACH AND INTESTINE MUST BE EMPTIED. A. EMPTY THE STOMACH BY INTUBATION, ASPIRATION, AND LAVAGE, USING SLURRY OF ACTIVATED CHARCOAL IN ISOTONIC SALINE. RIGOROUS PRECAUTIONS MUST BE TAKEN TO PROTECT THE AIRWAY FROM ASPIRATION OF REGURGITATED. IF VICTIM IS UNCONSCIOUS OR OBTUNDED, INSERT A CUFFED ENDOTRACHEAL TUBE PRIOR TO GASTRIC INTUBATION. KEEP VICTIM'S HEAD BELOW LEVEL OF STOMACH DURING GASTRIC INTUBATION AND LAVAGE ... . KEEP VICTIM'S HEAD TURNED TO THE LEFT. /ORGANOPHOSPHATE PESTICIDES/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

迅速通过皮肤吸收。

Rapidly absorbed through skin.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• [EN] COMPOSITIONS AND METHODS FOR IMMUNE MODULATION AND TREATMENT OF CANCER<br/>[FR] COMPOSITIONS ET MÉTHODES DE MODULATION IMMUNITAIRE ET DE TRAITEMENT DU CANCER
  申请人：UNIV MICHIGAN STATE

  公开号：WO2020150668A1

  公开（公告）日：2020-07-23

  The disclosure relates to rexinoids, including compounds of the Formula (I) and (II) or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof. These rexinoids are useful for increasing PD-L1 in vivo, for treatment of cancer, and for inhibiting the onset of cancer.

  该披露涉及雷克西酮，包括式(I)和(II)的化合物或其药用可接受的盐、多型体、前药、溶剂合物或包合物。这些雷克西酮对于体内增加PD-L1，在癌症治疗中以及抑制癌症发生方面是有用的。
• [EN] ALLOSTERIC AGONISTS AND POSITIVE ALLOSTERIC MODULATORS OF GLUCAGON-LIKE PEPTIDE 1 RECEPTOR<br/>[FR] AGONISTES ALLOSTÉRIQUES ET MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR DU GLUCAGON-LIKE PEPTIDE 1
  申请人：UNIV OF THE SCIENCES

  公开号：WO2020210582A1

  公开（公告）日：2020-10-15

  The present invention relates to the discovery of small molecule compounds that act act as GLP-1R agonists and/or as positive allosteric modulators (PAMs) of GLP-1R. Such compounds are useful to treat, ameliorate, and/or prevent insulin resistance and/or diabetes in a mammal.

  本发明涉及发现作为GLP-1R激动剂和/或GLP-1R的正向变构调节子（PAMs）的小分子化合物。这些化合物可用于治疗、改善和/或预防哺乳动物体内的胰岛素抵抗和/或糖尿病。
• [EN] SULFONYL COMPOUNDS AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE-1<br/>[FR] COMPOSÉS DE SULFONYLE COMME INHIBITEURS DE LA 11-BÉTA-HYDROXYSTÉROIDE DÉSHYDROGÉNASE-1
  申请人：MERCK & CO INC

  公开号：WO2006017542A1

  公开（公告）日：2006-02-16

  Sulfonyl derivatives of structural formula I are selective inhibitors of the 11β-hydroxysteroid dehydrogenase-1. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome or Syndrome X, and other symptoms associated with NIDDM.

  结构式I的磺酰衍生物是11β-羟基类固醇脱氢酶-1的选择性抑制剂。这些化合物可用于治疗糖尿病，如非胰岛素依赖型糖尿病（NIDDM）、高血糖、肥胖、胰岛素抵抗、血脂异常、高脂血症、高血压、代谢综合征或X综合征，以及与NIDDM相关的其他症状。
• Substituted piperidine compounds
  申请人：——

  公开号：US20040186135A1

  公开（公告）日：2004-09-23

  Novel 3,4-disubstituted-4-aryl-piperidine compounds are disclosed. Pharmaceutical compositions containing the 3,4-disubstituted-4-aryl-piperidine compounds and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as antagonists of opioid receptors.

  公开了新型的3,4-二取代-4-芳基哌啶化合物。还公开了包含3,4-二取代-4-芳基哌啶化合物的药物组合物及其药物用途的方法。所公开的化合物可用作阿片受体拮抗剂等。
• [EN] QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE QUINAZOLINE EN TANT QU'INHIBITEURS DE KINASE
  申请人：FENG YANGBO

  公开号：WO2010056758A1

  公开（公告）日：2010-05-20

  The invention is directed to quinazoline compounds that can inhibit the bioactivity of one or more kinase enzymes, including a Rho kinase, an AKT kinase, a p70S6K kinase, a LIM kinase, an IKK kinase, a Fit kinase, an Aurora kinase, or a Src kinase, or any combination thereof; to methods of use of those compounds; and to methods of preparation of those compounds. The inventive compounds can be used in the treatment of malconditions including cardiovascular disease, neurogenic pain, hypertension, atherosclerosis, angina, stroke, arterial obstruction, peripheral arterial disease, erectile dysfunction, acute and chronic pain, dementia, Alzheimer's disease, Parkinson's disease, neuronal degeneration, asthma, amyotrophic lateral sclerosis, spinal cord injury, rheumatoid arthritis, osteoarthritis, osteoporosis, psoriasis, cerebral vasospasm, open angle glaucoma, multiple sclerosis, pulmonary hypertension, acute respiratory distress syndrome, inflammation, diabetes, urinary organ diseases and benign prostatic hypertrophy (BPH), metastasis, cancer, glaucoma, ocular hypertension, retinopathy, autoimmune disease, viral infection, or myocardial pathology.

  这项发明涉及能够抑制一个或多个激酶酶的生物活性的喹唑啉化合物，包括Rho激酶、AKT激酶、p70S6K激酶、LIM激酶、IKK激酶、Fit激酶、Aurora激酶或Src激酶，或其任意组合；这些化合物的使用方法；以及这些化合物的制备方法。这些创新化合物可用于治疗包括心血管疾病、神经性疼痛、高血压、动脉粥样硬化、心绞痛、中风、动脉阻塞、周围动脉疾病、勃起功能障碍、急性和慢性疼痛、痴呆症、阿尔茨海默病、帕金森病、神经元退化、哮喘、肌萎缩侧索硬化、脊髓损伤、类风湿性关节炎、骨关节炎、骨质疏松症、银屑病、脑血管痉挛、开角型青光眼、多发性硬化、肺动脉高压、急性呼吸窘迫综合征、炎症、糖尿病、泌尿器官疾病和良性前列腺增生（BPH）、转移、癌症、青光眼、眼压增高、视网膜病变、自身免疫疾病、病毒感染或心肌病理的恶性疾病的治疗。