6-chloro-3-methyl-[1,2,4]triazolo[3,4-a]phthalazine | 67458-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-chloro-3-methyl-[1,2,4]triazolo[3,4-a]phthalazine
• CAS: 67458-38-2
• 化学式: C₁₀H₇ClN₄
• mdl: MFCD00593954
• 分子量: 218.645
• InChiKey: KBOSDDNHLXFFIB-UHFFFAOYSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)
• 溶解度：
  22.1 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  6-chloro-3-methyl-[1,2,4]triazolo[3,4-a]phthalazine 在 四(三苯基膦)钯 、 potassium carbonate 、 三乙胺 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 5.0h， 生成 4-methyl-N-(5-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)-2-morpholinophenyl)benzenesulfonamide
  参考文献：
  名称：

  [1,2,4]Triazolo[4,3-a]phthalazines: Inhibitors of Diverse Bromodomains

  摘要：

  Bromodomains are gaining increasing interest as drug targets. Commercially sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines are potent inhibitors of both the BET bromodomains such as BRD4 as well as bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new series of compounds. is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily. Representative compounds are active in cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP and chromatin association. The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology.

  DOI：

  10.1021/jm401568s
• 作为产物：
  描述：

  1,4-二氯酞嗪 在 hydrazine hydrate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 0.5h， 生成 6-chloro-3-methyl-[1,2,4]triazolo[3,4-a]phthalazine
  参考文献：
  名称：

  新型1,2,4-三唑[3,4- a ]酞嗪衍生物的合成及抑菌活性

  摘要：

  从常见的前体邻苯二甲酸酐分五个步骤合成了一系列新型的1,2,4-三唑并[3,4- a ]酞嗪衍生物。大多数合成的酞嗪衍生物对金黄色葡萄球菌均具有抑制作用。酞嗪衍生物5l之一显示出对所有测试的细菌和真菌菌株的抑制活性。

  DOI：

  10.1016/j.bmcl.2013.12.010

文献信息

• [EN] TRIAZOLO-PYRIDAZINE COMPOUNDS AND DERIVATIVES THEREOF USEFUL IN THE TREATMENT OF NEUROPATHIC PAIN<br/>[FR] COMPOSES DE TRIAZOLO-PYRIDAZINE ET LEURS DERIVES, DESTINES AU TRAITEMENT DE LA DOULEUR NEUROPATHIQUE
  申请人：MERCK & CO INC

  公开号：WO2005041971A1

  公开（公告）日：2005-05-12

  The present invention is directed to a method of use of triazolo-pyridazine compounds in the treatment of neuropathic pain. The present invention is also directed to the use of triazolo-pyridazine compounds in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, bipolar disorders, and panic, as well as in the treatment of pain, Parkinson’s disease, cognitive dysfunction, epilepsy, circadian rhythm and sleep disorders - such as shift-work induced sleep disorder and jet-lag, drug addiction, drug abuse, drug withdrawal and other diseases. The present invention is also directed to novel triazolo-pyridazine compounds that selectively bind to α2δ-1 subunit of Ca channels.

  本发明涉及一种在治疗神经病性疼痛中使用三唑吡啶化合物的方法。本发明还涉及在治疗精神和情绪障碍，如精神分裂症、焦虑、抑郁、躁郁症和恐慌，以及在治疗疼痛、帕金森病、认知功能障碍、癫痫、昼夜节律和睡眠障碍（如倒班引起的睡眠障碍和时差反应）、药物成瘾、药物滥用、药物戒断和其他疾病中使用三唑吡啶化合物的方法。本发明还涉及选择性结合到Ca通道α2δ-1亚基的新型三唑吡啶化合物。
• Discovery of a PCAF Bromodomain Chemical Probe
  作者：Moses Moustakim、Peter G. K. Clark、Laura Trulli、Angel L. Fuentes de Arriba、Matthias T. Ehebauer、Apirat Chaikuad、Emma J. Murphy、Jacqui Mendez‐Johnson、Danette Daniels、Chun‐Feng D. Hou、Yu‐Hui Lin、John R. Walker、Raymond Hui、Hongbing Yang、Lucy Dorrell、Catherine M. Rogers、Octovia P. Monteiro、Oleg Fedorov、Kilian V. M. Huber、Stefan Knapp、Jag Heer、Darren J. Dixon、Paul E. Brennan

  DOI：10.1002/anie.201610816

  日期：2017.1.16

  bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished

  p300 / CBP相关因子（PCAF）和相关的GCN5含溴结构域的赖氨酸乙酰基转移酶是溴结构域系统发育树的亚家族I的成员。合理的抑制剂设计和生物物理特征的反复循环导致发现了基于三唑并噻嗪的L-45（称为L-Moses）作为第一种有效的，选择性的和具有细胞活性的PCAF溴结构域（Brd）抑制剂。由易于获得的（1R，2S）-（-）-去氧麻黄碱合成的对映纯形式的L-45。L-45显示出扰乱使用nanoBRET测定细胞PCAF-BRD组蛋白H3.3相互作用，和的共晶体结构L-45与来自恶性疟原虫的同源Brd PfGCN5的组合合理化了对PCAF和GCN5溴结构域的高选择性。化合物L-45在外周血单核细胞（PBMC）中没有可观察到的细胞毒性，在人和小鼠肝微粒体中没有良好的细胞渗透性和代谢稳定性，支持其在体内使用的潜力。
• Synthesis and anticancer activities of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives
  作者：Deng-Qi Xue、Xu-Yao Zhang、Chao-Jie Wang、Li-Ying Ma、Nan Zhu、Peng He、Kun-Peng Shao、Peng-Ju Chen、Yi-Fei Gu、Xiao-Song Zhang、Cai-Feng Wang、Cong-Hui Ji、Qiu-Rong Zhang、Hong-Min Liu

  DOI：10.1016/j.ejmech.2014.07.031

  日期：2014.10

  Trying to develop potent and selective anticancer agents, two series of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives were designed and synthesized. Their antitumor activities were evaluated by MTT method against four selected human cancer cell lines (MGC-803, EC-9706, HeLa and MCF-7). Our results showed that compound 11h exhibited good anticancer activities compared to 5-fluorouracil against

  为了开发有效的和选择性的抗癌药，设计并合成了两个系列的新型1,2,4-三唑并[3,4-a]酞嗪衍生物。通过MTT方法评估了它们对四种选择的人类癌细胞系（MGC-803，EC-9706，HeLa和MCF-7）的抗肿瘤活性。我们的结果表明，与5-氟尿嘧啶相比，化合物11h对四种受试细胞系表现出良好的抗癌活性，IC 50值范围为2.0至4.5μM。流式细胞仪分析表明，化合物11h在EC-9706中诱导了G2 / M期的细胞早期凋亡和细胞周期停滞。
• Discovery of novel triazolophthalazine derivatives as DNA intercalators and topoisomerase II inhibitors
  作者：Helmy Sakr、Rezk R. Ayyad、Ali A. El‐Helby、Mohamed M. Khalifa、Hazem A. Mahdy

  DOI：10.1002/ardp.202000456

  日期：2021.6

  A new series of triazolophthalazine derivatives was designed and synthesized as topoisomerase II (Topo II) inhibitors and DNA intercalators. The synthesized derivatives were evaluated in vitro for their cytotoxic activities against three human cancer cell lines: HepG2, MCF-7, and HCT-116 cells. Compound IXb was the most potent counterpart with IC50 values of 5.39 ± 0.4, 3.81 ± 0.2, and 4.38 ± 0.3 µM

  设计并合成了一系列新的三唑并酞嗪衍生物作为拓扑异构酶 II (Topo II) 抑制剂和 DNA 嵌入剂。在体外评估了合成的衍生物对三种人类癌细胞系的细胞毒活性：HepG2、MCF-7 和 HCT-116 细胞。化合物IX b是最有效的对应物，IC 50值为 5.39 ± 0.4、3.81 ± 0.2 和 4.38 ± 0.3 µM，因为它的活性大约是阿霉素的 1.47、1.77 和 1.19 倍（IC 50  = 7.6,4 ± 6.75 ± 0.4 和 5.23 ± 0.3 µM）分别针对 HepG2、MCF-7 和 HCT-116 细胞。此外，合成化合物对 DNA 分子的结合亲和力使用 DNA/甲基绿测定进行评估。化合物 Ⅸ b显示出优异的 DNA 结合亲和力，IC 50值为 27.16 ± 1.2 µM，优于参考药物阿霉素 (IC 50  = 31.02 ± 1.80 µM)。此外，当研究它们的
• Triazolo-Pyridazine Compounds and Derivatives Thereof Useful in the Treatment of Neuropathic Pain
  申请人：Lebsack D. Alec

  公开号：US20070213338A1

  公开（公告）日：2007-09-13

  The present invention is directed to a method of use of triazolo-pyridazine compounds in the treatment of neuropathic pain. The present invention is also directed to the use of triazolo-pyridazine compounds in the treatment of psychiatric and mood disorders such as, for example, schizophrenia, anxiety, depression, bipolar disorders, and panic, as well as in the treatment of pain, Parkinson's disease, cognitive dysfunction, epilepsy, circadian rhythm and sleep disorders—such as shift-work induced sleep disorder and jet-lag, drug addiction, drug abuse, drug withdrawal and other diseases. The present invention is also directed to novel triazolo-pyridazine compounds that selectively bind to α 2 δ-1 subunit of Ca channels.

  本发明涉及一种使用三唑并吡嗪化合物治疗神经病性疼痛的方法。本发明还涉及使用三唑并吡嗪化合物治疗精神和情绪障碍，例如精神分裂症、焦虑、抑郁、双相障碍和惊恐症，以及治疗疼痛、帕金森病、认知功能障碍、癫痫、昼夜节律和睡眠障碍（例如倒班引起的睡眠障碍和时差反应）、药物成瘾、药物滥用、药物戒断和其他疾病的方法。本发明还涉及新型的三唑并吡嗪化合物，它们能够选择性地结合到Ca通道的α2δ-1亚基上。