R-138727 | 204204-73-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: R-138727
• 英文别名: (2Z)-1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylideneethanoic acid；(Z)-3-carboxymethylidene-1-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4-mercaptopiperidine；(2Z)-2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene]acetic acid
• CAS: 204204-73-9
• 化学式: C₁₈H₂₀FNO₃S
• 分子量: 349.426
• InChiKey: ZWUQVNSJSJHFPS-XFXZXTDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

R-138727是普拉格雷的一种含有巯基的活性代谢产物，是一种不可逆的血小板P2Y12受体抑制剂，能够有效抑制ADP诱导的血小板聚集。

反应信息

• 作为反应物：
  描述：

  二甲基亚砜 、 R-138727 在 乙二胺四乙酸 作用下， 以 aq. phosphate buffer 为溶剂， 生成 R-106583(普拉格雷代谢物)
  参考文献：
  名称：

  Hepatic Microsomal Thiol Methyltransferase Is Involved in Stereoselective Methylation of Pharmacologically Active Metabolite of Prasugrel

  摘要：

  RS和RR异构体。

  DOI：

  10.1124/dmd.114.057661
• 作为产物：
  描述：

  普拉格雷 在 水 、 氧气 、 三(2-羰基乙基)磷盐酸盐 、 还原型辅酶II(NADPH)四钠盐 、 cytochrome P₄₅₀ 作用下， 生成 R-138727
  参考文献：
  名称：

  氯吡格雷和普拉格雷的生物激活：硫醇代谢物双键立体化学的决定因素。

  摘要：

  四氢噻吩并吡啶系列的抗血栓药氯吡格雷和普拉格雷是前药，必须在两个步骤中代谢才能具有药理活性。第一步是形成硫代内酯代谢物。第二步是进一步氧化，形成硫代内酯亚砜，其水解开口导致亚磺酸，亚磺酸最终被还原成相应的活性顺式硫醇。关于具有双键反式构型的活性顺式硫醇异构体的形成的数据很少，在这方面最引人注目的结果是顺式和反式都在存在谷胱甘肽（GSH）的情况下，人肝微粒体在氯吡格雷的代谢中形成了硫醇，而用该药物治疗的患者血清中仅检测到顺式硫醇。该文章表明，在存在GSH的情况下，普拉格雷或其硫代内酯代谢物的微粒体代谢也会形成反式硫醇，并且只有在存在硫醇的情况下进行微粒体温育时，才会形成具有双键反式构型的代谢物。如GSH，N-乙酰半胱氨酸和巯基乙醇。由GSH与硫代内酯亚砜代谢产物反应形成的硫酯的中间形成似乎是造成反式的原因硫醇的形成。在微粒体温育中添加人肝细胞溶质导致反式硫醇代谢物形成的急剧减少。这些数据表明

  DOI：

  10.1021/acs.chemrestox.5b00133

文献信息

• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF ATHEROTHROMBOSIS<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR LE TRAITEMENT DE L'ATHÉROTROMBOSE
  申请人：KANDULA MAHESH

  公开号：WO2013024376A1

  公开（公告）日：2013-02-21

  The disclosures herein provide compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for peroral administration- transdermal administration, transmucosal, syrups, topical, extended release, sustained release, or injection. Such compositions may foe used to treatment of vascular disorders or conditions such as thrombotic cerebrovascular or cardiovascular disease or its associated complications.

  本公开提供公式I的化合物或其药用可接受的盐，以及其多晶型、对映体、立体异构体、溶剂合物和水合物。这些盐可以制成药物组合物。药物组合物可以用于口服、经皮、经粘膜、糖浆、局部、延长释放、持续释放或注射的给药。这种组合物可用于治疗血管疾病或病况，如血栓性脑血管或心血管疾病或其相关并发症。
• 3-Phenyl-pyrazole derivatives as modulators of the 5-HT2a serotonin receptor useful for the treatment of disorders related thereto
  申请人：Teegarden Bradley

  公开号：US20070207994A1

  公开（公告）日：2007-09-06

  The present invention relates to certain 3-phenyl-pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  本发明涉及某些3-苯基-吡唑衍生物，其具有公式(Ia)和调节5-HT2A血清素受体活性的药物组合物。这些化合物及其药物组合物用于治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、房颤、降低血块形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、抽动秽语综合征、躁狂症、有机或NOS精神病、精神疾病、急性精神分裂症、慢性精神分裂症、NOS精神分裂症及相关障碍，以及睡眠障碍、糖尿病相关障碍、进行性多灶性脑白质病等。本发明还涉及与其他药物一起或分别给药治疗5-HT2A血清素受体介导的疾病的方法。
• 3-Phenyl-Pyrazole Derivatives as Modulators of the 5-Ht2A Serotonin Receptor Useful for the Treatment of Disorders Related Thereto
  申请人：Teegarden Bradley

  公开号：US20070244086A1

  公开（公告）日：2007-10-18

  The present invention relates to certain 3-phenyl-pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  本发明涉及某些3-苯基吡唑衍生物（Ia式）及其药物组成物，其调节5-HT2A 5-羟色胺受体的活性。该化合物及其药物组成物针对的方法有用于治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、心房颤动、减少血栓形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、吉尔·德·拉·图雷特综合征、躁狂障碍、器质性或非器质性精神病、精神病、急性精神分裂症、慢性精神分裂症、非特异性精神分裂症及相关疾病、睡眠障碍、糖尿病相关疾病、进行性多灶性白质脑病等。本发明还涉及用于治疗5-HT2A 5-羟色胺受体介导的疾病的方法，该方法与其他药物剂量分别或同时给药。
• Pyrazole Derivatives as Modulators of the 5-Ht2a Serotonin Receptor Useful for the Treatment of Disorders Related Thereto
  申请人：Strah-Pleynet Sonja

  公开号：US20080015223A1

  公开（公告）日：2008-01-17

  The present invention relates to certain pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, sleep disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  本发明涉及式（Ia）的某些吡唑衍生物及其制药组合物，其调节5-HT2A 5-羟色胺受体的活性。该化合物和制药组合物适用于治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、房颤、降低血栓形成的风险、哮喘或其症状、激动或症状、行为障碍、药物诱导性精神病、兴奋性精神病、Gilles de la Tourette综合症、躁狂障碍、器质性或NOS精神病、精神病性障碍、精神病、急性精神分裂症、慢性精神分裂症、NOS精神分裂症及相关疾病、睡眠障碍、糖尿病相关疾病、进行性多灶性白质脑病等的治疗方法。本发明还涉及与其他分开或联合给药的制药剂一起治疗5-HT2A 5-羟色胺受体介导的疾病的方法。
• CRYSTALLINE FORMS OF CERTAIN 3-PHENYL-PYRAZOLE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Stirn Scott

  公开号：US20120252813A1

  公开（公告）日：2012-10-04

  Provided are certain solvates of 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions comprising such solvates and methods for their use.

  提供了3-甲氧基-N-[3-(2-甲基-2H-吡唑-3-基)-4-(2-吗啡啉-4-基-乙氧基)-苯基]-苯甲酰胺或其药学上可接受的盐的某些溶剂化物。还提供了包含这种溶剂化物的制药组合物以及使用它们的方法。