3-苯基-1H-吡唑并[3,4-d]嘧啶-4-胺 | 42754-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-苯基-1H-吡唑并[3,4-d]嘧啶-4-胺
• 英文名称: 3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: 3-phenyl-2H-pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 42754-69-8
• 化学式: C₁₁H₉N₅
• 分子量: 211.226
• InChiKey: JPWZTNIDHIJKIS-UHFFFAOYSA-N

物化性质

• 熔点：
  276 °C
• 沸点：
  350.8±52.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-苯基-1H-吡唑并[3,4-d]嘧啶-4-胺 在 sodium carbonate 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二甲基亚砜 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 27.0h， 生成 2-(4-((4-amino-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-(4-chlorophenyl)ethanone
  参考文献：
  名称：

  Synthesis of 3-phenylpyrazolopyrimidine-1,2,3-triazole conjugates and evaluation of their Src kinase inhibitory and anticancer activities

  摘要：

  A series of two classes of 3-phenylpyrazolopyrimidine-1,2,3-triazole conjugates were synthesized using click chemistry approach. All compounds were evaluated for inhibition of Src kinase and human ovarian adenocarcinoma (SK-Ov-3), breast carcinoma (MDA-MB-361), and colon adenocarcinoma (HT-29). Hexyl triazolyl-substituted 3-phenylpyrazolopyrimidine exhibited inhibition of Src kinase with an IC50 value of 5.6 mu M. 4-Methoxyphenyl triazolyl-substituted 3-phenylpyrazolopyrimidine inhibited the cell proliferation of HT-29 and SK-Ov-3 by 73% and 58%, respectively, at a concentration of 50 mu M. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.047
• 作为产物：
  描述：

  (α-morpholinobenzylidene)malononitrile 在 一水合肼 作用下， 反应 3.0h， 生成 3-苯基-1H-吡唑并[3,4-d]嘧啶-4-胺
  参考文献：
  名称：

  Tominaga, Yoshinori; Matsuoka, Yoshiki; Oniyama, Yukio, Journal of Heterocyclic Chemistry, 1990, vol. 27, # 3, p. 647 - 660

  摘要：

  DOI：

文献信息

• Adenosine Kinase Inhibitors. 6. Synthesis, Water Solubility, and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-β-<scp>d</scp>-ribofuranosyl)pyrrolo[2,3-<i>d</i>]pyrimidines Substituted at C4 with Glycinamides and Related Compounds
  作者：Brett C. Bookser、Bheemarao G. Ugarkar、Michael C. Matelich、Robert H. Lemus、Matthew Allan、Megumi Tsuchiya、Masami Nakane、Atsushi Nagahisa、James B. Wiesner、Mark D. Erion

  DOI：10.1021/jm050394a

  日期：2005.12.1

  4-(Phenylamino)-5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 1 and related compounds known as "diaryltubercidin" analogues are potent inhibitors of adenosine kinase (AK) and are orally active in animal models of pain such as the rat formalin paw model (GP3269 ED50= 6.4 mg/kg). However, the utility of this compound class is limited by poor water solubility that can be attributed

  4-（苯氨基）-5-苯基-7-（5-脱氧-β-D-呋喃呋喃糖基）吡咯并[2,3-d]嘧啶1和相关化合物被称为“二芳基丁二醛”类似物，是腺苷激酶（AK）的有效抑制剂。 ），并且在疼痛动物模型（例如大鼠福尔马林爪模型（GP3269 ED50 = 6.4 mg / kg））中具有口服活性。但是，该化合物类别的实用性受到水溶性差的限制，这可归因于固态的平行C4和C5芳基环的堆叠（化合物1和GP3269的pH 7.4溶解度< 0.05微克/毫升）。为了增加水溶性，疏水性C 4-苯基氨基取代基被更亲水的甘氨酰胺取代。该修饰导致改善的水溶性，同时保持AK抑制效力。研究了类似物，其中甘氨酰胺部分的变化与碱基和糖的变化结合在一起。铅化合物4-N-（N-环丙基氨基甲酰基甲基）氨基-5-苯基-7-（5-脱氧-β-D-呋喃呋喃糖基）吡咯并[2,3-d]嘧啶（16c）（IC50 = 3 nM在pH 7.4时，水溶解度=
• [EN] 1,2-DITHIOLANE COMPOUNDS USEFUL IN NEUROPROTECTION, AUTOIMMUNE AND CANCER DISEASES AND CONDITIONS<br/>[FR] COMPOSÉS 1,2-DITHIOLANE UTILES DANS LA NEUROPROTECTION, LES MALADIES ET LES ÉTATS AUTO-IMMUNS ET CANCÉREUX
  申请人：SABILA BIOSCIENCES LLC

  公开号：WO2018049127A1

  公开（公告）日：2018-03-15

  This invention provides confounds of the formula (I): wherein Y1, Y2 Z, X1, X2, and W are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and Ρ13K/ΑΚΤ/mTor signaling pathway kinases-mediated diseases; or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3 -ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROSI; MAPK pathway kinases selected from ARAF, BRAE CRAP, ERK1 /2, MEK1, MEK2, MEK3, MEK4, MEK5. MEK6, and MEK7; and P13K/AKT/mTor pathway kinases: selected from mTor, P13K a, Ρ13Κ β, P13Kγ, and P13K δ.

  这项发明提供了公式（I）的混合物：其中Y1、Y2、Z、X1、X2和W在规范中定义。这些化合物在治疗酪氨酸激酶、MAPK信号通路激酶和Ρ13K/ΑΚΤ/mTor信号通路激酶介导的疾病；或病况中有用，如神经退行性疾病、神经保护、癌症、自身免疫以及与选择自FYN、FYN Y531F、FLT3、FLT3-ITD、BRK、ITK、FRK、BTK、BMX、SRC、FGR、YES1、LCK、HCK、RET、CSK、LYN和ROSI的酪氨酸激酶调节相关的其他疾病和病况；从ARAF、BRAE CRAP、ERK1/2、MEK1、MEK2、MEK3、MEK4、MEK5、MEK6和MEK7中选择的MAPK通路激酶；以及P13K/AKT/mTor通路激酶：从mTor、P13Kα、Ρ13Κβ、P13Kγ和P13Kδ中选择。
• [EN] ATG7 INHIBITORS AND THE USES THEREOF<br/>[FR] INHIBITEURS D'ATG7 ET LEURS UTILISATIONS
  申请人：MILLENNIUM PHARM INC

  公开号：WO2018089786A1

  公开（公告）日：2018-05-17

  Disclosed are chemical entities which are compounds of formula (I) : or a pharmaceutically acceptable salt thereof, wherein R1, R2, and Ra have the values described herein. Chemical entities according to the disclosure can be useful as inhibitors of ATG7. Further provided are pharmaceutical compositions comprising a chemical entity of the disclosure and methods of using the compositions in the treatment of cancer.

  本公开涉及化学实体，其为以下式（I）的化合物：或其药学上可接受的盐，其中R1、R2和Ra具有此处描述的值。根据本公开的化学实体可以用作ATG7的抑制剂。还提供了包括本公开的化学实体的药物组合物以及使用这些组合物治疗癌症的方法。
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：Honigberg Lee

  公开号：US20080076921A1

  公开（公告）日：2008-03-27

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

  本文披露了与Bruton酪氨酸激酶（Btk）形成共价键的化合物。还描述了Btk的不可逆抑制剂。披露了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。披露了使用Btk抑制剂的方法，单独或与其他治疗药物结合，用于治疗自身免疫疾病或状况、异体免疫疾病或状况、癌症，包括淋巴瘤，以及炎症性疾病或状况。
• 1,3‐Disubstituted‐4‐Aminopyrazolo [3, 4‐d] Pyrimidines, a New Class of Potent Inhibitors for Phospholipase <scp>D</scp>
  作者：Aditya Kulkarni、Phong Quang、Victoriana Curry、Renee Keyes、Weihong Zhou、Hyejin Cho、Jonathan Baffoe、Béla Török、Kimberly Stieglitz

  DOI：10.1111/cbdd.12319

  日期：2014.9

  Phospholipase D enzymes cleave lipid substrates to produce phosphatidic acid, an important precursor for many essential cellular molecules. Phospholipase D is a target to modulate cancer‐cell invasiveness. This study reports synthesis of a new class of phospholipase D inhibitors based on 1,3‐disubstituted‐4‐amino‐pyrazolopyrimidine core structure. These molecules were synthesized and used to perform initial

  磷脂酶D酶裂解脂质底物以产生磷脂酸，磷脂酸是许多必需细胞分子的重要前体。磷脂酶D是调节癌细胞侵袭性的靶标。这项研究报告了基于1,3-二取代-4-氨基-吡唑并嘧啶核心结构的新型磷脂酶D抑制剂的合成。这些分子被合成并用于为纯化的细菌磷脂酶d的抑制，这是高度同源的人的PLD执行初步筛选1。最初用细菌磷脂酶D酶进行测试，然后用重组人PLD 1和PLD 2酶确认，此处显示的分子表现出对磷脂酶D活性的抑制作用（IC 50）在低纳摩尔至低微摩尔范围内，同时具有单体底物diC 4 PC和磷脂囊泡和胶束。数据强烈表明这些抑制分子直接阻断了酶/囊泡底物的结合。初步活性研究使用重组人磷脂酶Ds在体内细胞测定中测量了转磷脂酰化和头部裂解，表明在生理环境中这些有效的抑制性新分子在中低纳摩尔范围内具有抑制作用。