N-(3-(6-(4-((2S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide | 1133432-50-4

• 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: N-(3-(6-(4-((2S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide
• 英文别名: (S)-N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide；N-[3-(6-{4-[(2S)-1,4-Dimethyl-3-oxopiperazin-2-yl]anilino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide；N-[3-[6-[4-[(2S)-1,4-dimethyl-3-oxopiperazin-2-yl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide
• CAS: 1133432-50-4
• 化学式: C₃₃H₃₆N₆O₃S
• 分子量: 596.753
• InChiKey: CDOOFZZILLRUQH-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  43
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 储存条件：
  -20℃

制备方法与用途

GDC-0834的S型异构体（GDC-0834 S-enantiomer）活性较低，而GDC-0834是一种有效的、选择性的BTK抑制剂。

反应信息

• 作为产物：
  描述：

  GDC-0834 在 N-[3-[6-[[4-(1,4-二甲基-3-氧代-2-哌嗪基)苯基]氨基]-4,5-二氢-4-甲基-5-氧代-2-吡嗪基]-2-甲基苯基]-4,5,6,7-四氢苯并[b]噻吩-2-甲酰胺 、 异丙醇 、 正庚烷 、 三氟乙酸 、 N-(3-(6-(4-((2S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide 、 氯仿 、 GDC-0834 作用下， 以 氯仿 为溶剂， 反应 1.68h， 以to give individual enantiomers at 4.6 minutes (20) ((−) isomer) ([α]D25=−37.8° (c=3.75, CHCl3), mp=181-183° C.)的产率得到N-(3-(6-(4-((2S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide
  参考文献：
  名称：

  CERTAIN SUBSTITUTED AMIDES, METHOD OF MAKING, AND METHOD OF USE THEREOF

  摘要：

  本文描述了抑制Btk的I式化合物。描述了包含至少一种I式化合物的制药组合物，以及至少选择自载体、佐剂和辅料中的一种药用可接受载体。描述了治疗对Btk活性和/或B细胞活性抑制有反应的某些疾病的患者的方法。还描述了检测样品中Btk存在的方法。

  公开号：

  US20090082330A1
• 作为试剂：
  描述：

  GDC-0834 在 N-[3-[6-[[4-(1,4-二甲基-3-氧代-2-哌嗪基)苯基]氨基]-4,5-二氢-4-甲基-5-氧代-2-吡嗪基]-2-甲基苯基]-4,5,6,7-四氢苯并[b]噻吩-2-甲酰胺 、 异丙醇 、 正庚烷 、 三氟乙酸 、 N-(3-(6-(4-((2S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide 、 氯仿 、 GDC-0834 作用下， 以 氯仿 为溶剂， 反应 1.68h， 以to give individual enantiomers at 4.6 minutes (20) ((−) isomer) ([α]D25=−37.8° (c=3.75, CHCl3), mp=181-183° C.)的产率得到N-(3-(6-(4-((2S)-1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide
  参考文献：
  名称：

  Certain substituted pyrazinones

  摘要：

  本文描述了一些化学式为I的化合物，它们可以抑制Btk。还描述了包含至少一种化合物I的药物组合物，以及至少一种从载体、佐剂和赋形剂中选择的药用接受者。本文还描述了治疗某些对抑制Btk活性和/或B细胞活性敏感的疾病的患者的方法。还描述了一种确定样品中Btk存在的方法。

  公开号：

  US07884108B2

文献信息

• Certain Substituted Amides, Method of Making, and Method of Use Thereof
  申请人：Blomgren Peter A.

  公开号：US20110059944A1

  公开（公告）日：2011-03-10

  Compounds of Formula I that inhibit Btk are described herein. Pharmaceutical compositions comprising at least one compound of Formula I, together with at least one pharmaceutically acceptable vehicle chosen from carriers, adjuvants, and excipients, are described. Methods of treating patients suffering from certain diseases responsive to inhibition of Btk activity and/or B-cell activity are described. Methods for determining the presence of Btk in a sample are described.

  本文描述了抑制Btk的化合物I的配方。本文还描述了包括至少一种化合物I的制药组合物，以及至少一种从载体、佐剂和赋形剂中选择的药用可接受载体。本文还描述了治疗对抑制Btk活性和/或B细胞活性敏感的某些疾病的患者的方法。本文还描述了检测样品中Btk存在的方法。
• THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS
  申请人：BROWN Dennis M.

  公开号：US20160045502A1

  公开（公告）日：2016-02-18

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

  本发明描述了一种改善先前受到治疗性能不佳限制的治疗剂的治疗效果的方法和组合物，通过改善单药疗法的功效或减少副作用。这种方法和组合物特别适用于芥子碱基烷基化剂，例如尿嘧啶芥和其类似物、衍生物或前药，包括6-甲基尿嘧啶芥和6-乙基尿嘧啶芥。
• Treatment and prevention of atherothrombosis by inhibition of bruton's tyrosine kinase (BTK)
  申请人：Siess Wolfgang

  公开号：US10786509B2

  公开（公告）日：2020-09-29

  The present invention relates to an inhibitor of Bruton's tyrosine kinase (Btk) for use in the treatment and/or prevention of atherothrombosis. The present invention further relates to a method of treating and/or preventing atherothrombosis comprising administering a pharmaceutically effective amount of an inhibitor of Bruton's tyrosine kinase (Btk) to a subject in need thereof.

  本发明涉及一种用于治疗和/或预防动脉粥样硬化血栓形成的布鲁顿酪氨酸激酶（Btk）抑制剂。本发明进一步涉及一种治疗和/或预防动脉粥样硬化血栓形成的方法，该方法包括向有需要的受试者施用药学有效量的布鲁顿酪氨酸激酶（Btk）抑制剂。
• SUBSTITUTED AMIDES, METHODS OF MAKING, USE THEREOF FOR THE TREATMENT OF DISEASES SUCH AS CANCER
  申请人：Gilead Connecticut, Inc.

  公开号：EP2188267B1

  公开（公告）日：2016-08-03
• METHOD OF TREATING RESISTANT NON-HODGKIN LYMPHOMA, MEDULLOBLASTOMA, AND/OR ALK+NON-SMALL CELL LUNG CANCER USING THIENOTRIAZOLODIAZEPINE COMPOUNDS
  申请人：ONCOETHIX GMBH

  公开号：US20170095484A1

  公开（公告）日：2017-04-06

  A method of treating resistant non-Hodgkin lymphoma, medulloblastoma, and/or ALK+ non-small cell lung cancer in a mammal by administering a solid dispersion comprising an amorphous thienotriazolodiazepine compound of the Formula (1) wherein R′ is alkyl having a carbon number of 1-4, R2 is a hydrogen atom; a halogen atom; or alkyl having a carbon number of 1-4 optionally substituted by a halogen atom or a hydroxyl group, R3 is a halogen atom; phenyl optionally substituted by a halogen atom, alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4 or cyano; —NR 5-CH 2)m-, —R6 wherein R5 is a hydrogen atom or alkyl having a carbon number of 1-4, m is an integer of 0-4, and R6 is phenyl or pyridyl optionally substituted by a halogen atom.