2-(4-chlorophenyl)imidazo[1,2-a]pyrimidine-3-carbaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-chlorophenyl)imidazo[1,2-a]pyrimidine-3-carbaldehyde
• 化学式: C₁₃H₈ClN₃O
• mdl: MFCD04966860
• 分子量: 257.679
• InChiKey: LNUYRKFYGCLLJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 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：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)imidazo[1,2-a]pyrimidine-3-carbaldehyde 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 N-((2-(4-chlorophenyl)imidazo[1,2-a]pyrimidin-3-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：

  对氯苯乙酮 在 N-溴代丁二酰亚胺(NBS) 、 三氯氧磷 作用下， 以 甘油 为溶剂， 反应 0.23h， 生成 2-(4-chlorophenyl)imidazo[1,2-a]pyrimidine-3-carbaldehyde
  参考文献：
  名称：

  甘油中2-芳基咪唑并[1,2-a]嘧啶-3-甲醛的便捷高效微波辅助合成

  摘要：

  摘要 2-苯基咪唑并[1,2-a]嘧啶与（Vilsmeier-Haack试剂）反应合成2-芳基咪唑并[1,2-a]嘧啶-3-甲醛的简单高效方法在 400 瓦、90 °C 的微波辐射下，甘油作为绿色反应介质存在。反应条件温和、收率高、反应时间短、反应曲线干净、避免使用有毒催化剂、有害有机溶剂、废料少是以往采用的方法的优点。

  DOI：

  10.1080/00397911.2022.2158746

文献信息

• [EN] SUBSTITUTED BRIDGED DIAZEPANE DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS DE DIAZÉPANE PONTÉS SUBSTITUÉS ET LEUR UTILISATION
  申请人：BAYER AG

  公开号：WO2018227427A1

  公开（公告）日：2018-12-20

  The present application relates to novel imidazopyridinyl-or imidazopyrimidinyl-substituted, bridged 1,4-diazepane derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of respiratory disorders including, sleep-related respiratory disorders such as obstructive sleep apnoeas and central sleep apnoeas and snoring.

  本申请涉及新型咪唑吡啶基或咪唑嘧啶基取代的、桥联的1,4-二氮杂环庚烷衍生物，以及它们的制备方法，单独或组合用于治疗和/或预防疾病，以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防呼吸系统疾病，包括与睡眠有关的呼吸系统疾病，如阻塞性睡眠呼吸暂停症、中枢性睡眠呼吸暂停症和打鼾。
• DIAZABICYCLIC SUBSTITUTED IMIDAZOPYRIMIDINES AND THEIR USE FOR THE TREATMENT OF BREATHING DISORDERS
  申请人：Bayer Aktiengesellschaft

  公开号：US20200109155A1

  公开（公告）日：2020-04-09

  The present invention relates to novel diazabicyclically substituted imidazo[1,2-a]pyrimidine derivatives, to methods for producing the same, to the use thereof either alone or in combinations for the treatment and/or prevention of diseases, as well as to their use for preparing medicaments for the treatment and/or prevention of diseases, especially for treatment and/or prevention of breathing disorders, including sleep-related breathing disorders such as obstructive and central sleep apnoea and snoring.

  本发明涉及新型的二氮杂双环取代咪唑[1,2-a]嘧啶衍生物，以及制备它们的方法。本发明还涉及它们的单独或联合使用用于治疗和/或预防疾病，以及用于制备药物用于治疗和/或预防疾病，特别是用于治疗和/或预防呼吸障碍，包括睡眠相关呼吸障碍，例如阻塞性和中枢性睡眠呼吸暂停和鼾症。
• Substituted bridged diazepane derivatives and use thereof as TASK-1 and TASK-3 inhibitors
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：US11208422B2

  公开（公告）日：2021-12-28

  The present application relates to novel imidazopyridinyl- or imidazopyrimidinyl-substituted, bridged 1,4-diazepane derivatives of formula (I), to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of respiratory disorders including, sleep-related respiratory disorders such as obstructive sleep apnoeas and central sleep apnoeas and snoring. Formula (I) in which the ring Q represents a bridged 1,4-diazepane cycle.

  本申请涉及新型咪唑吡啶基或咪唑嘧啶基取代的、桥接的式(I)1,4-二氮杂环庚烷衍生物，涉及其制备工艺，涉及其单独使用或组合使用以治疗和/或预防疾病，涉及其用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防呼吸系统疾病，包括与睡眠有关的呼吸系统疾病，如阻塞性睡眠呼吸暂停和中枢性睡眠呼吸暂停以及打鼾。式（I）中，环 Q 代表桥接的 1，4-二氮杂环。
• SUBSTITUTED BRIDGED DIAZEPANE DERIVATIVES AND USE THEREOF AS TASK-1 AND TASK-3 INHIBITORS
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP3638676A1

  公开（公告）日：2020-04-22
• 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.