3-(3-甲基磺酰基氧基丙基氨基)丙基甲烷磺酸酯盐酸盐 | 3458-22-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 中文名称: 3-(3-甲基磺酰基氧基丙基氨基)丙基甲烷磺酸酯盐酸盐
• 英文名称: Improsulfan hydrochloride
• 英文别名: 3-(3-methylsulfonyloxypropylamino)propyl methanesulfonate;hydrochloride
• CAS: 3458-22-8
• 化学式: C8H20ClNO6S2
• 分子量: 325.8
• InChiKey: YWCASUPWYFFUHE-UHFFFAOYSA-N

物化性质

• 熔点：
  94-95°
• 颜色/状态：
  Crystals
• 分解：
  When heated to decomposition it emits very toxic fumes of HCl, /nitric oxides, and sulfer oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  -4.71
• 重原子数：
  18
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫并视需要治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔并给予5毫升/千克，最多200毫升的水进行稀释……。在去污染后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常。开始静脉输液，使用D5W /SRP: "保持开放"，最低流速。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/两百零八名可接受的患者接受了Yoshi 864治疗（2毫克/千克/天，静脉推注，连续5天，每6周重复一次）。毒性最小。整体反应率为11%。可能不存在与其他烷化剂的交叉耐药性。由于其毒性较低，Yoshi 864应该进一步在慢性髓细胞性白血病、淋巴瘤、卵巢和膀胱癌中进行评估，因为这些疾病中观察到了显著的反应。它还应该作为其他引起更多恶心和呕吐的烷化剂的替代品进行评估。

/HUMAN EXPOSURE STUDIES/ Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/ Yoshi 864 通过静脉推注每日一次，连续5天，并随访6周。剂量递增从0.25 mg/kg到2.7 mg/kg。在1.5 mg/kg时首次观察到毒性和有效性。有16位患者在达到或超过这一水平时接受了25个疗程。在22个疗程中（不包括慢性髓性白血病CML），有16个疗程出现了血小板减少和/或白细胞减少。平均血小板和白细胞最低点发生在第24天和第29天，恢复需要1-2周和2-3周。有11个疗程出现了血红蛋白下降。在2.7 mg/kg时，3个疗程中的患者在6-12天内出现了恶心和呕吐；在5个疗程中，患者每天睡眠20小时，其中1个疗程患者昏迷了2天。2名鳞状细胞癌患者和1名原发灶不明患者有反应。2名慢性髓性白血病患者出现了临床缓解。建议在广泛的人类实体肿瘤（包括淋巴瘤和慢性髓细胞性白血病）中进行合作性的II期研究，剂量水平为2 mg/kg。

/HUMAN EXPOSURE STUDIES/ Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/ Yoshi-864 显著延长了携带 L1210 白血病或艾氏腹水癌的小鼠的生存时间。与 Yoshi-864 具有相同甲磺酸酯离去基团的白消安（Busulfan）无效。经 Yoshi-864 处理的携带艾氏肿瘤的小鼠的肿瘤细胞在合成 DNA 的能力上持续降低。经白消安处理的小鼠细胞在治疗 48 小时后 DNA 合成受到中等程度的抑制，但在 72 小时后几乎恢复到对照组的值。

/LABORATORY ANIMALS: Acute Exposure/ Yoshi-864 extends markedly the survival times of mice bearing L1210 leukemia or Ehrlich ascites carcinoma. Busulfan, with methanesulfonate leaving groups identical with those of Yoshi-864, is without effect. Tumor cells from mice bearing the Ehrlich tumor and treated with Yoshi-864 have a persistent reduction in ability to synthesize DNA. Synthesis of DNA in cells from mice treated with busulfan is moderately suppresed at 48 hr after treatment, but returns virtually to the control value at 72 hr.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• [EN] PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIMIDINE ET DE TRIAZINE, ET LEUR UTILISATION COMME INHIBITEURS D'AXL
  申请人：PFIZER

  公开号：WO2016097918A1

  公开（公告）日：2016-06-23

  Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.

  公式(I)的化合物： (I) 这些化合物的制备方法，包含这些化合物的组合物，以及这些化合物的用途。
• Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060046991A1

  公开（公告）日：2006-03-02

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了式1的对映纯化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。
• [EN] BENZIMIDAZOLE OR INDOLE AMIDES AS INHIBITORS OF PIN1<br/>[FR] AMIDES DE BENZIMIDAZOLE OU D'INDOLE EN TANT QU'INHIBITEURS DE PIN1
  申请人：PFIZER

  公开号：WO2006040646A1

  公开（公告）日：2006-04-20

  The invention relates to compounds of the formula (1) and to pharmaceutically acceptable salts and solvates thereof, wherein the variables are defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula (1) and to pharmaceutical compositions for treating such disorders that contain the compounds of formula (1). The invention also relates to methods of preparing the compounds of formula (1).

  这项发明涉及公式（1）的化合物，以及其药学上可接受的盐和溶剂化合物，其中变量在此处定义。该发明还涉及通过给予公式（1）的化合物来治疗哺乳动物中的异常细胞生长的方法，以及用于治疗包含公式（1）化合物的这类疾病的药物组合物。该发明还涉及制备公式（1）化合物的方法。
• [EN] AMINOHETEROARYL COMPOUNDS AS PROTEIN TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSES AMINOHETEROARYLES EN TANT QU'INHIBITEURS DES PROTEINES TYROSINE KINASES
  申请人：PFIZER

  公开号：WO2006021886A1

  公开（公告）日：2006-03-02

  Aminoheteroaryl compounds are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了氨基杂环芳基化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。
• 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation
  申请人：McAlpine James Indrawan

  公开号：US20050090529A1

  公开（公告）日：2005-04-28

  3,5 disubstituted indazole compounds with substituted nitrogen bearing 5-membered heterocycles in the 3-position that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating CDK dependent diseases to modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  描述了在3-位置带有取代氮的5-成员杂环的3,5-二取代吲唑化合物，这些化合物调节和/或抑制细胞增殖，如蛋白激酶活性。这些化合物和含有它们的药物组合物能够调节和/或抑制介导CDK依赖性疾病的不需要的细胞增殖。该发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予这些化合物的有效量来治疗癌症以及与不需要的血管生成和/或细胞增殖相关的其他疾病状态，如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣的方法。