FN-1501 | 1429515-59-2

• 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: FN-1501
• 英文别名: 4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide；LT-171-861；Fn-1501；N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide
• CAS: 1429515-59-2
• 化学式: C₂₂H₂₅N₉O
• 分子量: 431.5
• InChiKey: VXLAKHWYGRKCGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(4-甲基哌嗪-1-基甲基)苯胺 在 FeO(OH)/C 、 1-羟基苯并三唑 、 一水合肼 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 FN-1501
  参考文献：
  名称：

  Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia

  摘要：

  A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical for FLT3 and CDK inhibition. Compound 50 (FN-1501), which possesses potent inhibitory activities against FLT3, CDK2, CDK4, and CDK6 with IC50 values in the nanomolar range, shows antiproliferative activities against MV4-11 cells (IC50: 0.008 mu M), which correlates with the suppression of retinoblastoma phosphorylation, FLT3, ERK, AKT, and STAT5 and the onset of apoptosis. Acute-toxicity studies in mice show that compound 50 (LD50: 186 mg/kg) is safer than AT7519 (32 mg/kg). In MV4-11 xenografts in a nude-mouse model, compound 50 can induce tumor regression at the dose of 15 mg/kg, which is more efficient than cytarabine (50 mg/kg). Taken together, these results demonstrate the potential of this unique compound for further development into a drug applied in acute-myeloid-leukemia (AML) therapeutics.

  DOI：

  10.1021/acs.jmedchem.7b01261

文献信息

• [EN] COVALENT CDK2-BINDING COMPOUNDS FOR THERAPEUTIC PURPOSES<br/>[FR] COMPOSÉS DE LIAISON À CDK2 COVALENTS UTILISÉS À DES FINS THÉRAPEUTIQUES
  申请人：UMBRA THERAPEUTICS INC

  公开号：WO2022187693A1

  公开（公告）日：2022-09-09

  Heteroaryl sulfonyl compounds and compositions that have a CDK2 Recognition Moiety bound to an electrophile for the selective covalent modification of CDK2 to treat CDK2-mediated disorders are described.

  本文描述了具有CDK2识别基团结合到亲电体的杂环磺酰化合物和组合物，用于选择性共价修饰CDK2以治疗CDK2介导的疾病。
• [EN] MEDICINE FOR TREATING OR PREVENTING DISEASES RELATED TO ACTIVITY OF LRRK2 KINASE OR ABNORMAL LRRK2 MUTANT KINASE<br/>[FR] MÉDICAMENT POUR LE TRAITEMENT OU LA PRÉVENTION DE MALADIES LIÉES À L'ACTIVITÉ DE LA KINASE LRRK2 OU DE LA KINASE MUTANTE LRRK2 ANORMALE<br/>[ZH] 一种治疗或预防与LRRK2激酶或异常LRRK2突变激酶活性相关疾病的药物
  申请人：[en]DM INTELLIGENCE LTD.;[zh]广州智睿医药科技有限公司

  公开号：WO2022062357A1

  公开（公告）日：2022-03-31

  一种治疗或预防与LRRK2激酶或异常LRRK2突变激酶活性相关疾病的药物，属于医药领域。所述药物包括化学式1表示的化合物、其光学异构体、其前体药物、其盐、其水合物、其溶剂化物、其N-氧化物、其氘化类似物中的至少一种，对LRRK2激酶或异常LRRK2突变激酶具有很好的抑制作用，能用于治疗或预防与LRRK2激酶或异常LRRK2突变激酶活性相关疾病，例如阿兹海默氏症、L多巴诱发性运动障碍、帕金森氏病、痴呆症、肾癌、乳腺癌、前列腺癌、血癌、乳头状瘤、肺癌、急性骨髓性白血病、多发性骨髓瘤、麻风病、克罗恩氏病、炎症性肠病、溃疡性结肠炎、肌肉萎缩性侧索硬化、类风湿性关节炎或强直性脊椎炎。
• J. Med. Chem. 2018, 61, 1499-1518
  作者：

  DOI：——

  日期：——
• Discovery of 4-((7<i>H</i>-Pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)amino)-<i>N</i>-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1<i>H</i>-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia
  作者：Yue Wang、Yanle Zhi、Qiaomei Jin、Shuai Lu、Guowu Lin、Haoliang Yuan、Taotao Yang、Zhanwei Wang、Chao Yao、Jun Ling、Hao Guo、Tonghui Li、Jianlin Jin、Baoquan Li、Li Zhang、Yadong Chen、Tao Lu

  DOI：10.1021/acs.jmedchem.7b01261

  日期：2018.2.22

  A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical for FLT3 and CDK inhibition. Compound 50 (FN-1501), which possesses potent inhibitory activities against FLT3, CDK2, CDK4, and CDK6 with IC50 values in the nanomolar range, shows antiproliferative activities against MV4-11 cells (IC50: 0.008 mu M), which correlates with the suppression of retinoblastoma phosphorylation, FLT3, ERK, AKT, and STAT5 and the onset of apoptosis. Acute-toxicity studies in mice show that compound 50 (LD50: 186 mg/kg) is safer than AT7519 (32 mg/kg). In MV4-11 xenografts in a nude-mouse model, compound 50 can induce tumor regression at the dose of 15 mg/kg, which is more efficient than cytarabine (50 mg/kg). Taken together, these results demonstrate the potential of this unique compound for further development into a drug applied in acute-myeloid-leukemia (AML) therapeutics.