N-(3-(2-oxo-2,3-dihydro-1H-thieno[3,4-b][1,4]diazepine-4-yl)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide

• 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-(2-oxo-2,3-dihydro-1H-thieno[3,4-b][1,4]diazepine-4-yl)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide
• 英文别名: N-(3-(2-oxo-2,3-dihydro-1H-thieno[3,4-b][1,4]diazepin-4-yl)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide；N-[3-(4-oxo-3,5-dihydrothieno[3,4-b][1,4]diazepin-2-yl)phenyl]-1-phenyl-5-(trifluoromethyl)pyrazole-4-carboxamide
• 化学式: C₂₄H₁₆F₃N₅O₂S
• 分子量: 495.485
• InChiKey: MPCNIVXZJDGXIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-硝基苯甲酰乙酸乙酯 在 铁粉 、 氯化铵 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.17h， 生成 N-(3-(2-oxo-2,3-dihydro-1H-thieno[3,4-b][1,4]diazepine-4-yl)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  发现靶向多种蛋白激酶的新型4-芳基-噻吩并[1,4]二氮杂-2-酮衍生物作为抗癌剂。

  摘要：

  合成了一系列4-芳基-噻吩并[1,4]二氮杂-2--2-酮，并评估了它们对A375P黑色素瘤和U937造血细胞系的抗增殖活性。几种化合物对两种细胞系均表现出非常强的抗增殖活性，其活性优于参考标准索拉非尼。制备了具有各种疏水性部分的酰胺（8a-8i，9a-9m）和尿素（10a-10d，11a-11d）。最有效的抑制剂10d之一，1-（4-（（4-乙基哌嗪-1-基）甲基）-3-（三氟甲基）苯基）-3-（4-（2-氧代-2,3-二氢-发现1H-噻吩并[3,4-b] [1,4]二氮杂pin-4-基）苯基）脲是包括FMS激酶在内的多种蛋白激酶的强效抑制剂（IC50 = 3.73 nM），是一种有前途的候选药物用于癌症治疗的进一步发展。

  DOI：

  10.1016/j.bmc.2018.02.009

文献信息

• THIENODIAZEPINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus

  公开号：US20180037589A1

  公开（公告）日：2018-02-08

  The present invention relates to novel thienodiazepine derivatives or pharmaceutically acceptable salts thereof, and a pharmaceutical composition including the same. The thienodiazepine derivatives or pharmaceutically acceptable salts thereof exhibit selective inhibition activities against protein kinases such as c-Kit, FLT3, FMS, LYN, RAF1, VEGFR3, PDGFRa, PDGFRb, RET, etc., and thus can be used as a pharmaceutical composition for prevention or treatment of abnormal cell growth diseases.

  本发明涉及新型噻二唑啉衍生物或其药用盐，以及包括它们的药物组合物。这些噻二唑啉衍生物或其药用盐对蛋白激酶如c-Kit、FLT3、FMS、LYN、RAF1、VEGFR3、PDGFRa、PDGFRb、RET等表现出选择性抑制活性，因此可用作预防或治疗异常细胞生长疾病的药物组合物。
• Thienodiazepine derivatives or pharmaceutically acceptable salts thereof, and pharmaceutical composition including the same as an active ingredient
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus

  公开号：US10174047B2

  公开（公告）日：2019-01-08

  The present invention relates to novel thienodiazepine derivatives or pharmaceutically acceptable salts thereof, and a pharmaceutical composition including the same. The thienodiazepine derivatives or pharmaceutically acceptable salts thereof exhibit selective inhibition activities against protein kinases such as c-Kit, FLT3, FMS, LYN, RAF1, VEGFR3, PDGFRa, PDGFRb, RET, etc., and thus can be used as a pharmaceutical composition for prevention or treatment of abnormal cell growth diseases.

  本发明涉及新型噻二氮卓衍生物或其药学上可接受的盐，以及包括其在内的药物组合物。噻二氮卓衍生物或其药学上可接受的盐类对蛋白激酶如 c-Kit、FLT3、FMS、LYN、RAF1、VEGFR3、PDGFRa、PDGFRb、RET 等具有选择性抑制活性，因此可用作预防或治疗异常细胞生长疾病的药物组合物。
• [EN] THIENODIAZEPINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT<br/>[FR] DÉRIVÉ THIÉNODIAZÉPINE OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CE DERNIER, ET COMPOSITION PHARMACEUTIQUE LE CONTENANT EN TANT QUE PRINCIPE ACTIF<br/>[KO] 티에노디아제핀 유도체 또는 이의 약학적으로 허용가능한 염, 및 이를 유효성분으로 포함하는 약학적 조성물
  申请人：INDUSTRY-UNIV COOP FOUND HANYANG UNIV ERICA CAMPUS

  公开号：WO2016137060A1

  公开（公告）日：2016-09-01

  본 발명은 신규한 티에노디아제핀 유도체, 이의 약학적으로 허용가능한 염, 및 이를 포함하는 약학적 조성물에 관한 것이다. 본 발명에 따른 티에노디아제핀 유도체 또는 이의 약학적으로 허용가능한 염은 c-Kit, FLT3, FMS, LYN, RAF1, VEGFR3, PDGFRa, PDGFRb, RET 등과 같은 단백질 키나아제에 대해 선택적인 저해 활성을 나타내어 비정상 세포 성장 질환의 예방 또는 치료용 약학적 조성물로 이용될 수 있다.
• Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting multiple protein kinases as anticancer agents
  作者：Junghun Lee、Hoyong Jung、Minjung Kim、Eunkyu Lee、Daseul Im、Waqar Aman、Jung-Mi Hah

  DOI：10.1016/j.bmc.2018.02.009

  日期：2018.5

  A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Several compounds showed very potent antiproliferative activities toward both cell lines and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide (8a-8i, 9a-9m) and urea (10a-10d

  合成了一系列4-芳基-噻吩并[1,4]二氮杂-2--2-酮，并评估了它们对A375P黑色素瘤和U937造血细胞系的抗增殖活性。几种化合物对两种细胞系均表现出非常强的抗增殖活性，其活性优于参考标准索拉非尼。制备了具有各种疏水性部分的酰胺（8a-8i，9a-9m）和尿素（10a-10d，11a-11d）。最有效的抑制剂10d之一，1-（4-（（4-乙基哌嗪-1-基）甲基）-3-（三氟甲基）苯基）-3-（4-（2-氧代-2,3-二氢-发现1H-噻吩并[3,4-b] [1,4]二氮杂pin-4-基）苯基）脲是包括FMS激酶在内的多种蛋白激酶的强效抑制剂（IC50 = 3.73 nM），是一种有前途的候选药物用于癌症治疗的进一步发展。