1H-pyrrolo[2,3-b]pyridine-3-carbohydrazide | 310887-39-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1H-pyrrolo[2,3-b]pyridine-3-carbohydrazide
• CAS: 310887-39-9
• 化学式: C₈H₈N₄O
• mdl: MFCD19690324
• 分子量: 176.178
• InChiKey: RCTKDOLLKSLHGB-UHFFFAOYSA-N

物化性质

• 密度：
  1.436±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1H-pyrrolo[2,3-b]pyridine-3-carbohydrazide 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[(1R)-1-phenylpropyl]-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  The optimization of aminooxadiazoles as orally active inhibitors of Cdc7

  摘要：

  A series of aminooxadiazoles was optimized for inhibition of Cdc7. Early lead isoquinoline 1 suffered from modest cell potency (cellular IC50 = 0.71 mu M measuring pMCM2), low selectivity against structurally related kinases, and high IV clearance in rats (CL = 18 L/h/kg). Extensive optimization resulted in azaindole 26 (Cdc7 IC50 = 1.1 nM, pMCM2 IC50 = 32 nM) that demonstrated robust lowering of pMCM2 in a mouse pharmacodynamic (PD) model when dosed orally. Modifications to improve the pharmacokinetic profile of this series were guided by trapping experiments with glutathione in rat hepatocytes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.055
• 作为产物：
  描述：

  1H-吡咯并[2,3-B]吡啶-3-羧酸甲酯 在 肼 作用下， 以 甲醇 、 水 为溶剂， 反应 21.0h， 生成 1H-pyrrolo[2,3-b]pyridine-3-carbohydrazide
  参考文献：
  名称：

  [EN] OXADIAZOLE DERIVATIVES AND THEIR USE AS NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS
  [FR] DÉRIVÉS D'OXADIAZOLE ET LEUR UTILISATION COMME MODULATEURS DES RÉCEPTEURS NICOTINIQUES DE L'ACÉTYLCHOLINE

  摘要：

  Oxadiazole衍生物的化学式（I），其中环A是一个双环或三环系统。所述化合物对尼古丁型乙酰胆碱受体（nAChRs）具有活性，并可用于治疗神经系统、精神病学和胃肠道疾病，以及败血症和肥胖症。

  公开号：

  WO2009071577A1

文献信息

• [EN] HEPARANASE INHIBITORS AND USE THEREOF<br/>[FR] INHIBITEURS D'HÉPARANASE ET LEUR UTILISATION
  申请人：BETA THERAPEUTICS PTY LTD

  公开号：WO2018107200A1

  公开（公告）日：2018-06-21

  The invention relates to functionalized quinazoline compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds as heparanase inhibitors for the treatment of diseases or conditions related to heparanse activity.

  本发明涉及功能化喹唑啉化合物，包括此类化合物的药物组合物，以及此类化合物作为肝素酶抑制剂用于治疗与肝素酶活性相关的疾病或状况的使用。
• 7-AZAINDOLE DERIVATIVES
  申请人：Klein Markus

  公开号：US20110166175A1

  公开（公告）日：2011-07-07

  Novel 7-azaindole derivatives of the formula (I), in which U, L, R, Y, X 1 , X 2 and X 3 have the meanings indicated in Claim 1 ), are kinase inhibitors and can be used for the treatment of diseases and conditions such as diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and kidney diseases, generally in any type of fibroses, inflammatory processes, tumours and tumour diseases.

  小说7-氮杂吲哚衍生物的化学式（I），其中U、L、R、Y、X1、X2和X3具有声明中指示的含义，是激酶抑制剂，可用于治疗疾病和病况，如糖尿病、肥胖症、代谢综合征（血脂异常）、系统性和肺动脉高压、心血管疾病和肾脏疾病，通常在任何类型的纤维化、炎症过程、肿瘤和肿瘤疾病中。
• HETEROCYCLIC INHIBITORS OF RHO KINASE
  申请人：Borchardt J. Allen

  公开号：US20080021217A1

  公开（公告）日：2008-01-24

  The present invention relates to compounds and methods which may be useful as inhibitors of Rho kinase for the treatment or prevention of disease.

  本发明涉及化合物和方法，可以作为Rho激酶的抑制剂用于治疗或预防疾病。
• 7-azaindole derivatives
  申请人：Klein Markus

  公开号：US08466170B2

  公开（公告）日：2013-06-18

  Novel 7-azaindole derivatives of the formula (I), in which U, L, R, Y, X1, X2 and X3 have the meanings indicated in Claim (1), are kinase inhibitors and can be used for the treatment of diseases and conditions such as diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and kidney diseases, generally in any type of fibroses, inflammatory processes, tumors and tumor diseases.

  公式(I)的新颖的7-氮杂吲哚衍生物，其中U、L、R、Y、X1、X2和X3的含义如权利要求书(1)所示，是激酶抑制剂，可用于治疗疾病和病况，例如糖尿病、肥胖症、代谢综合征（血脂异常）、全身和肺动脉高压、心血管疾病和肾脏疾病，通常在任何类型的纤维化、炎症过程、肿瘤和肿瘤疾病中。
• 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1
  作者：Daniela Carbone、Camilla Pecoraro、Giovanna Panzeca、Geng Xu、Margot S. F. Roeten、Stella Cascioferro、Elisa Giovannetti、Patrizia Diana、Barbara Parrino

  DOI：10.3390/md21070412

  日期：——

  A new series of nortopsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, was efficiently synthesized. The antiproliferative activity of all synthesized derivatives was evaluated against five pancreatic ductal adenocarcinoma (PDAC) cell lines, a primary culture and a gemcitabine-resistant variant. The five more potent compounds elicited EC50 values in the submicromolar–micromolar range, associated with a significant reduction in cell migration. Moreover, flow cytometric analysis after propidium iodide staining revealed an increase in the G2-M and a decrease in G1-phase, indicating cell cycle arrest, while a specific ELISA demonstrated the inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation.

  我们高效合成了一系列新的去甲斑蝥素类似物，其中天然引线的中心咪唑环被1,3,4-噁二唑或1,3,4-噻二唑分子取代。针对五种胰腺导管腺癌（PDAC）细胞系、一种原代培养物和一种吉西他滨耐药变体，对所有合成衍生物的抗增殖活性进行了评估。这五种药效较强的化合物的 EC50 值在亚微摩-微摩范围内，并显著降低了细胞迁移。此外，碘化丙啶染色后进行的流式细胞分析表明，G2-M 期增加，G1 期减少，表明细胞周期停滞，而特异性酶联免疫吸附试验则表明 CDK1 活性受到抑制，CDK1 是细胞周期进展和癌细胞增殖的关键调节因子。