6-(4-bromophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde | 451485-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-(4-bromophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde
• 英文别名: 6-(4-Bromophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde
• CAS: 451485-66-8
• 化学式: C₁₂H₇BrN₂OS
• mdl: MFCD00268738
• 分子量: 307.17
• InChiKey: DERSRCNYCMEQSR-UHFFFAOYSA-N

物化性质

• 熔点：
  188-190°C
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  6-(4-bromophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 N-((6-(4-bromophenyl)imidazo[2,1-b]thiazol-5-yl)methyl)-2-(3,4-dichlorophenyl)ethan-1-amine
  参考文献：
  名称：

  Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies

  摘要：

  The DNA alkylating prodrug cyclophosphamide (CPA), alone or in combination with other agents, is one of the most commonly used anti-cancer agents. As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Therefore, hCAR agonists represent novel sensitizers for CPA-based therapies. Among known hCAR agonists, compound 6-(4-chlorophenyl)imidazo-[2,1-b]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) is the most potent and broadly utilized in biological studies. Through structural modification of CITCO, we have developed a novel compound DL5016 (32), which has an EC50 value of 0.66 mu M and E-MAX value of 4.9 when activating hCAR. DL5016 robustly induced the expression of hCAR target gene CYP2B6, at both the mRNA and protein levels, and caused translocation of hCAR from the cytoplasm to the nucleus in human primary hepatocytes. The effects of DL5016 were highlighted by dramatically enhancing the efficacy of CPA-based cytotoxicity to non-Hodgkin lymphoma cells. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.031
• 作为产物：
  描述：

  2,4'-二溴苯乙酮 在 三氯氧磷 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 22.0h， 生成 6-(4-bromophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde
  参考文献：
  名称：

  Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies

  摘要：

  The DNA alkylating prodrug cyclophosphamide (CPA), alone or in combination with other agents, is one of the most commonly used anti-cancer agents. As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Therefore, hCAR agonists represent novel sensitizers for CPA-based therapies. Among known hCAR agonists, compound 6-(4-chlorophenyl)imidazo-[2,1-b]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) is the most potent and broadly utilized in biological studies. Through structural modification of CITCO, we have developed a novel compound DL5016 (32), which has an EC50 value of 0.66 mu M and E-MAX value of 4.9 when activating hCAR. DL5016 robustly induced the expression of hCAR target gene CYP2B6, at both the mRNA and protein levels, and caused translocation of hCAR from the cytoplasm to the nucleus in human primary hepatocytes. The effects of DL5016 were highlighted by dramatically enhancing the efficacy of CPA-based cytotoxicity to non-Hodgkin lymphoma cells. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.031

文献信息

• [EN] THERAPEUTIC AGENTS<br/>[FR] AGENTS THERAPEUTIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2004058776A1

  公开（公告）日：2004-07-15

  A compound of the Formula: (I) (A chemical formula should be inserted here-please see paper copy enclosed herewith) Formula: (I); for use as a Tie2 receptor tyrosine kinase inhibitor in a warm-blooded animal such as man.

  一种化合物的化学式：（I）（这里应插入化学式，请参见附带的纸质副本）化学式：（I）；用作在温血动物（如人类）中的Tie2受体酪氨酸激酶抑制剂。
• Therapeutic agents
  申请人：Luke William Arthur Richard

  公开号：US20060069109A1

  公开（公告）日：2006-03-30

  A compound of the Formula: (I) (A chemical formula should be inserted here—please see paper copy enclosed herewith) Formula: (I); for use as a Tie2 receptor tyrosine kinase inhibitor in a warm-blooded animal such as man.

  化合物的化学式为：（I）（化学式应插入此处-请参阅随附的纸质副本）化学式：（I）； 用于作为Tie2受体酪氨酸激酶抑制剂在温血动物（如人）中使用。
• ANTI-ANGIOGENETIC THERAPEUTIC AGENTS
  申请人：AstraZeneca AB

  公开号：EP1575963B1

  公开（公告）日：2008-05-07
• THERAPEUTIC AGENTS
  申请人：AstraZeneca AB

  公开号：EP1575963A1

  公开（公告）日：2005-09-21
• CAR ACTIVATOR AGENTS FOR CYCLOPHOSPHAMIDE-BASED TREATMENTS OF CANCER
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE

  公开号：US20200352915A1

  公开（公告）日：2020-11-12

  The invention relates to selective small molecule human constitutive androstane receptor (hCAR) activators of Formula (I) or (II), pharmaceutical compositions thereof, and use thereof for the treatment of hematologic malignancies and other cancers. The small molecule hCAR activator in combination with CPA based chemotherapy regimen provides a synergistic effect to help promote cytoxicity of the cyclophosphamide (CPA) based anticancer treatments including CHOP regimen (CPA, doxorubicin, vincristine, and prednisone) by preferential induction of CYP2B6 over CYP3A4 and promoting the formation of therapeutically active CPA metabolite 4-OH-CPA.