(2-(4-methylpiperazin-1-yl)-5-nitrophenyl)methanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (2-(4-methylpiperazin-1-yl)-5-nitrophenyl)methanol
• 英文别名: [2-(4-Methylpiperazino)-5-nitrophenyl]methanol；[2-(4-methylpiperazin-1-yl)-5-nitrophenyl]methanol
• 化学式: C₁₂H₁₇N₃O₃
• mdl: MFCD09972261
• 分子量: 251.285
• InChiKey: WUDXWASLGUZIMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-(4-methylpiperazin-1-yl)-5-nitrophenyl)methanol 在 四丁基硫酸氢铵 、 铁粉 、 氯化铵 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 生成 3-((allyloxy)methyl)-4-(4-methylpiperazin-1-yl)aniline
  参考文献：
  名称：

  Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) Inhibitor for the Treatment of Myelofibrosis and Lymphoma

  摘要：

  Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (ME). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for ME and lymphoma.

  DOI：

  10.1021/jm200326p
• 作为产物：
  描述：

  2-氯-5-硝基苯甲醛 在 sodium tetrahydroborate 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 6.0h， 生成 (2-(4-methylpiperazin-1-yl)-5-nitrophenyl)methanol
  参考文献：
  名称：

  含嘧啶并二氢吡唑啉酮类衍生物、其药学上可接受的盐及其制备方法和应用

  摘要：

  本发明公开了一种含嘧啶并二氢吡唑啉酮类衍生物、其药学上可接受的盐及其制备方法和应用。本发明提供了一种含嘧啶并二氢吡唑啉酮类衍生物、其立体异构体或其药学上可接受的盐。该化合物能够抑制Wee1，且对Plk1具有较佳的选择性，可治疗癌症。

  公开号：

  CN115838375A

文献信息

• MACROCYCLIC COMPOUND SERVING AS WEE1 INHIBITOR AND APPLICATIONS THEREOF
  申请人：SHIJIAZHUANG SAGACITY NEW DRUG DEVELOPMENT CO., LTD.

  公开号：US20200325145A1

  公开（公告）日：2020-10-15

  Disclosed in the present invention are a macrocyclic compound serving as a Weel inhibitor, and applications thereof in the preparation of drugs for treating Weel-related diseases. The present invention specifically relates to a compound represented by formula (II), an isomer thereof, and a pharmaceutically acceptable salt thereof.

  本发明揭示了一种作为Weel抑制剂的大环化合物，以及在制备用于治疗与Weel相关疾病的药物中的应用。本发明具体涉及一种由式（II）表示的化合物，其异构体和其药用可接受的盐。
• [EN] PYRAZOLO-QUINAZOLINE DERIVATIVES,PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS<br/>[FR] DERIVES DE PYRAZOLO-QUINAZOLINE, PROCEDE DE PREPARATION ASSOCIE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE
  申请人：PHARMACIA ITALIA SPA

  公开号：WO2004104007A1

  公开（公告）日：2004-12-02

  Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  公开了配方(Ia)或(Ib)中定义的吡唑喹唑啉衍生物及其药用盐，其制备方法以及包含它们的药物组合物；本发明的化合物可能在治疗中对与异常蛋白激酶活性相关的疾病，如癌症，具有用处。
• MACROCYCLICS PYRIMIDINES AS AURORA KINASE INHIBITORS
  申请人：Yu Henry

  公开号：US20110294801A1

  公开（公告）日：2011-12-01

  Macrocyclic derivative compounds that inhibit protein kinase enzymes are disclosed along with pharmaceutical compositions comprising these compounds and methods for synthesizing the same. Such compounds have utility in the treatment of proliferative diseases resulting from unregulated and/or disturbed kinase activity such as cancers, psoriasis, viral and bacterial infections, inflammatory and autoimmune diseases.

  公开了抑制蛋白激酶酶的大环衍生物化合物，以及包括这些化合物的药物组合物和合成方法。这些化合物在治疗由于未受调控和/或受干扰的激酶活性导致的增殖性疾病方面具有用途，如癌症、银屑病、病毒和细菌感染、炎症和自身免疫疾病。
• 吡唑[3,4-d]嘧啶-3-酮的大环衍生物、其药物组合物及应用
  申请人：上海迪诺医药科技有限公司

  公开号：CN108623615B

  公开（公告）日：2022-12-13

  本发明涉及一种如式(I)所示的吡唑[3,4‑d]嘧啶‑3‑酮的大环衍生物和/或其药学上可接受的盐，以及含有如式(I)所示化合物的组合物和/或其药学上可接受的盐，制备方法和其作为Wee1抑制剂的用途及其作为癌症的化学疗法或放射性疗法的增敏剂中的用途；本发明的吡唑[3,4‑d]嘧啶‑3‑酮的大环衍生物可以有效的抑制Wee1及相关信号通路，具有良好的治疗和/或缓解癌症的作用。
• [EN] 7-CHLORO-QUINOLIN-4-AMINE COMPOUNDS AND USES THEREOF FOR THE PREVENTION OR TREATMENT OF DISEASES INVOLVING FORMATION OF AMYLOID PLAQUES AND/OR WHERE A DYSFUNCTION OF THE APP METABOLISM OCCURS<br/>[FR] COMPOSÉS DE 7-CHLORO-QUINOLIN-4-AMINE ET LEURS UTILISATIONS POUR PRÉVENIR OU TRAITER LES MALADIES IMPLIQUANT LA FORMATION DE PLAQUES AMYLOÏDES ET/OU UN DYSFONCTIONNEMENT DU MÉTABOLISME DE L'APP
  申请人：INST NAT SANTE RECH MED

  公开号：WO2011073322A1

  公开（公告）日：2011-06-23

  The present invention relates to compounds having the following Formula (I) for use in the prevention and/or the treatment of diseases involving formation of amyloid plaques and/or where a dysfunction of the APP metabolism occurs.

  本发明涉及具有以下式（I）的化合物，用于预防和/或治疗涉及淀粉样斑块形成和/或APP代谢功能障碍的疾病。