1-(4,6-dichloropyrimidin-2-yl)-2-(difluoromethyl)-1H-benzo[d]imidazole | 475111-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-(4,6-dichloropyrimidin-2-yl)-2-(difluoromethyl)-1H-benzo[d]imidazole
• 英文别名: 4,6-Dichloro-2-(2-difluoromethylbenzimidazol-1-yl)pyrimidine；1-(4,6-dichloropyrimidin-2-yl)-2-(difluoromethyl)benzimidazole
• CAS: 475111-27-4
• 化学式: C₁₂H₆Cl₂F₂N₄
• 分子量: 315.109
• InChiKey: GDTMVEYLMNKGAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-氨基吡啶 、 1-(4,6-dichloropyrimidin-2-yl)-2-(difluoromethyl)-1H-benzo[d]imidazole 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 以67%的产率得到6-chloro-2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(3-pyridinyl)-4-pyrimidinamine
  参考文献：
  名称：

  PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY

  摘要：

  本文提供了式I的嘧啶基和1,3,5-三嗪基苯并咪唑化合物，以及它们的药物组合物、制备方法，以及作为抗癌治疗药物或药剂的用途，可以单独使用，也可以与放疗和/或其他抗癌药物联合使用。

  公开号：

  US20110009405A1
• 作为产物：
  描述：

  邻苯二胺 在 盐酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 paraffin oil 为溶剂， 反应 3.5h， 生成 1-(4,6-dichloropyrimidin-2-yl)-2-(difluoromethyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A structure activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110 alpha, p110 beta, and p110 delta) and also displayed significant potency against two mutant forms of the p110 alpha isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Ragl(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd x 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.

  DOI：

  10.1021/jm200688y

文献信息

• [EN] SPIROCYCLIC COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES<br/>[FR] COMPOSÉS SPIROCYCLIQUES ET LEUR UTILISATION COMME AGENTS THÉRAPEUTIQUES ET SONDES DE DIAGNOSTIC
  申请人：UNIV BASEL

  公开号：WO2011114275A1

  公开（公告）日：2011-09-22

  The invention relates to new triazines (G = Q = U are N), pyrimidines (two out of G, Q and U are N), and pyridopyrimidines (one of G and U together with R2 forms an anullated pyridine ring) of formula (I) carrying a spirocyclic substituent, wherein E1 is CR4 or N; X1 is CHR4, CH2CH2, NR4, NR4→0, or O; and the other substituents are as defined in the specification. The compounds inhibit phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), DNA-PK and ATM kinase, and may be used as therapeutic agents or diagnostic probes. The invention also relates to methods of using the compounds for treatment of associated pathological conditions.

  本发明涉及新的三嗪类化合物（其中G = Q = U为N）、嘧啶类化合物（其中G、Q和U中的两个为N）和吡啶嘧啶类化合物（其中G和U中的一个与R2共同形成一个环状吡啶环），它们都带有一个螺环取代基，化学式为（I）。其中，E1为CR4或N；X1为CHR4、CH2CH2、NR4、NR4→0或O；其他取代基如规范中所定义。这些化合物能够抑制磷脂酰肌醇3-激酶（PI3K）、哺乳动物雷帕霉素靶蛋白酶（mTOR）、DNA-PK和ATM激酶，并可用作治疗剂或诊断探针。本发明还涉及使用这些化合物治疗相关病理条件的方法。
• SPIROCYCLIC COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS AND DIAGNOSTIC PROBES
  申请人：Cmiljanovic Vladimir

  公开号：US20130040934A1

  公开（公告）日：2013-02-14

  The invention relates to new triazines (G=Q=U are N), pyrimidines (two out of G, Q and U are N), and pyridopyrimidines (one of G and U together with R2 forms an anullated pyridine ring) of formula (I) carrying a spirocyclic substituent, wherein E 1 is CR 4 or N; X 1 is CHR 4 , CH 2 CH 2 , NR 4 , NR4→0, or O; and the other substituents are as defined in the specification. The compounds inhibit phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), DNA-PK and ATM kinase, and may be used as therapeutic agents or diagnostic probes. The invention also relates to methods of using the compounds for treatment of associated pathological conditions.

  该发明涉及具有螺环取代基的新三嗪类化合物（其中G=Q=U为N）、嘧啶类化合物（其中G、Q和U中的两个为N）和吡啶嘧啶类化合物（其中G和U中的一个与R2一起形成一个环状吡啶环）的化学式（I），其中E1为CR4或N；X1为CHR4、CH2CH2、NR4、NR4→0或O；其他取代基如规范中定义。这些化合物抑制磷脂酰肌醇3-激酶（PI3K）、哺乳动物雷帕霉素靶蛋白（mTOR）、DNA-PK和ATM激酶，并可用作治疗剂或诊断探针。该发明还涉及使用这些化合物治疗相关病理条件的方法。
• Heterocyclic compound and antitumor agent containing the same as effective ingredient
  申请人：Kawashima Seiichiro

  公开号：US20060247232A1

  公开（公告）日：2006-11-02

  The present invention relates to heterocyclic compounds represented by the formula I or pharmaceutically acceptable salts thereof and antitumor agents containing the heterocyclic compounds as effective components: wherein X represents nitrogen atom or CH; R 1 represents CH n F 3-n (wherein n is 1 or 2), hydroxy C 1 -C 6 alkyl, NHR 6 [wherein R 6 represents hydrogen atom or COR (wherein R represents hydrogen atom, C 1 -C 6 alkyl or C 1 -C 6 alkoxy)]; R 2 represents morpholino (which may be substituted with one to four C 1 -C 6 alkyl), thiomorpholino, piperidino, pyrrolidinyl (which may be substituted with hydroxy C 1 -C 6 alkyl), oxazolidinyl (which may be substituted with one or two C 1 -C 6 alkyl) or tetrahydro-1,4-thiazin-1-oxo-4-yl; R 3 and R 4 each represent hydrogen atom or C 1 -C 6 alkyl; and R 5 represents hydrogen atom, amino or hydroxyl.

  本发明涉及由式I表示的杂环化合物或其药学上可接受的盐，以及含有该杂环化合物作为有效成分的抗肿瘤剂： 其中X代表氮原子或CH；R1代表CHnF3-n（其中n为1或2），羟基C1-C6烷基，NHR6（其中R6代表氢原子或COR（其中R代表氢原子，C1-C6烷基或C1-C6烷氧基））；R2代表吗啡环（可以被取代为一到四个C1-C6烷基），硫代吗啡环，哌啶环，吡咯烷基（可以被羟基C1-C6烷基取代），噁唑烷基（可以被一到两个C1-C6烷基取代）或四氢-1,4-噻唑-1-氧-4-基；R3和R4各自代表氢原子或C1-C6烷基；R5代表氢原子，氨基或羟基。
• Heterocyclic compound and antitumor agent containing the same as active ingredient
  申请人：——

  公开号：US20040116421A1

  公开（公告）日：2004-06-17

  The present invention relates to heterocyclic compounds represented by the formula I or pharmaceutically acceptable salts thereof and antitumor agents containing the heterocyclic compounds as effective components: 1 wherein X represents nitrogen atom or CH; R 1 represents CH n F 3-n (wherein n is 1 or 2), hydroxy C 1 -C 6 alkyl, NHR 6 [wherein R 6 represents hydrogen atom or COR (wherein R represents hydrogen atom, C 1 -C 6 alkyl or C 1 -C 6 alkoxy)]; R 2 represents morpholino (which may be substituted with one to four C 1 -C 6 alkyl), thiomorpholino, piperidino, pyrrolidinyl (which may be substituted with hydroxy C 1 -C 6 alkyl), oxazolidinyl (which may be substituted with one or two C 1 -C 6 alkyl) or tetrahydro-1,4-thiazin- 1 -oxo-4-yl; R 3 and R 4 each represent hydrogen atom or C 1 -C 6 alkyl; and R 5 represents hydrogen atom, amino or hydroxyl.

  本发明涉及由式I表示的杂环化合物或其药学上可接受的盐以及含有该杂环化合物为有效成分的抗肿瘤剂： 1其中X代表氮原子或CH；R1代表CHnF3-n（其中n为1或2）、羟基C1-C6烷基、NHR6[其中R6代表氢原子或COR（其中R代表氢原子、C1-C6烷基或C1-C6烷氧基）]；R2代表吗啡啶基（可用一到四个C1-C6烷基取代）、硫代吗啡啶基、哌啶基、吡咯烷基（可用羟基C1-C6烷基取代）、噁唑烷基（可用一到两个C1-C6烷基取代）或四氢-1,4-噻唑-1-氧-4-基；R3和R4各自代表氢原子或C1-C6烷基；R5代表氢原子、氨基或羟基。
• Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy
  申请人：Rewcastle Gordon William

  公开号：US08486939B2

  公开（公告）日：2013-07-16

  Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.

  本文提供了式I中的嘧啶基和1,3,5-三嗪基苯并咪唑，以及它们的制备方法、药物组成物和用于癌症治疗的药物或药剂，可单独使用或与放射治疗和/或其他抗癌药物联合使用。