2-((1-methyl-1H-pyrazol-5-yl)amino)benzoic acid | 57861-03-7

• 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: 2-((1-methyl-1H-pyrazol-5-yl)amino)benzoic acid
• 英文别名: N-(1-Methylpyrazol-5-yl)-anthranilic acid；2-[(2-methylpyrazol-3-yl)amino]benzoic acid
• CAS: 57861-03-7
• 化学式: C₁₁H₁₁N₃O₂
• 分子量: 217.227
• InChiKey: UWZJRJNVMUGCIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  422.4±25.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-((1-methyl-1H-pyrazol-5-yl)amino)benzoic acid 在 三氯氧磷 作用下， 生成 4-chloro-1-methyl-1H-pyrazolo[3,4-b]quinoline
  参考文献：
  名称：

  Discovery and structure–activity relationship of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a new series of potent apoptosis inducers

  摘要：

  We report the discovery and SAR study of a series of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as potent inducers of apoptosis. N-(3-Acetylphenyl)-2,3-dihydro-1H-cyclopenta[b]quinolin-9-amine (2) was discovered through our cell- and caspase-based HTS assays as an inducer of apoptosis. Compound 2 is active against cancer cells derived from several human solid tumors, with EC50 values ranging from 400 to 700 nM. SAR study of hit 2 led to the discovery of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a novel series of potent apoptosis inducers, with 1,3-dimethyl-N-(4-propionylphenyl)-1H-pyrazolo[3,4-b]quinotin-amine (6b) having EC50 values ranging from 30 to 70 nM in cancer cells. These compounds also demonstrated potent activity in the cell growth inhibition assay, with GI(50) values of 16-42 nM for compound 6b. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.046
• 作为产物：
  描述：

  2-碘苯甲酸 、 1-甲基-5-氨基吡唑 在 copper(l) iodide 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以70%的产率得到2-((1-methyl-1H-pyrazol-5-yl)amino)benzoic acid
  参考文献：
  名称：

  作为有效SMO抑制剂的邻氨基苯甲酰胺衍生物的设计，合成和生物学评估。

  摘要：

  设计并合成了一系列邻氨基苯甲酰胺衍生物，作为基于SMO抑制剂taladegib（LY2940680）的新型平滑（SMO）抑制剂，后者也可以通过开环策略抑制SMO-D473H突变体。LY2940680中的酞嗪核心被蒽环酰胺取代，后者通过双重萤光素酶报告基因检测证实了对刺猬（Hh）信号通路的抑制活性。化合物12a对Hh信号通路表现出最佳的抑制活性，IC50值为34.09 nM，并且对Daoy细胞系的增殖抑制活性（IC50 = 0.48μM）比LY2940680（IC50 = 0.79μM）好。

  DOI：

  10.1016/j.bmc.2020.115354

文献信息

• 含苯甲酰哌啶结构的SMO抑制剂及其制备方 法与用途
  申请人：中国药科大学

  公开号：CN109734700B

  公开（公告）日：2021-09-28

  本发明公开了一种苯甲酰哌啶类衍生物及其制备方法和用途，所述苯甲酰哌啶类衍生物是一类含有N‑甲基‑N‑(1‑(2‑氨基苯甲酰基)哌啶‑4‑基)酰胺结构的化合物，其结构如式I所示。本发明还公开了所述苯甲酰哌啶类衍生物的制备方法。本发明还公开了所述苯甲酰哌啶类衍生物在制备SMO蛋白抑制剂中的应用，以及含有这些化合物的药物组合物在制备抗肿瘤药物方面的用途。
• Substituted N-Aryl-1H-Pyrazolo[3,4-B]Quinolin-4-Amines and Analogs as Activators of Caspases and Inducers of Apoptosis
  申请人：Zhang Han-Zhong

  公开号：US20070253957A1

  公开（公告）日：2007-11-01

  The present invention is directed to substituted N-aryl-1H-pyrazolo[3,4-b]quinolin-4-amines and analogs thereof, represented by the general Formula (I): wherein Q, Y, Z, R 4 -R 7 , X and Ar are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及被取代的N-芳基-1H-吡唑并[3,4-b]喹啉-4-胺及其类似物，其通式表示为（I）：其中Q，Y，Z，R4-R7，X和Ar在此被定义。本发明还涉及发现具有式（I）的化合物是caspase激活剂和凋亡诱导剂的事实。因此，本发明的caspase激活剂和凋亡诱导剂可用于在各种临床情况下诱导细胞死亡，其中发生异常细胞的无控制生长和扩散。
• [EN] SUBSTITUTED N-ARYL-1H-PYRAZOLO[3,4-b]QUINOLIN-4-AMINES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS<br/>[FR] N-ARYL-1H-PYRAZOLO[3,4-B]QUINOLIN-4-AMINES SUBSTITUES ET ANALOGUES UTILISES COMME ACTIVATEURS DE CASPASES ET INDUCTEURS DE L'APOPTOSE
  申请人：CYTOVIA INC

  公开号：WO2006041900A9

  公开（公告）日：2008-12-31
• Design, synthesis and biological evaluation of anthranilamide derivatives as potent SMO inhibitors
  作者：Dezhong Ji、Wanwan Zhang、Yungen Xu、Jing-Jing Zhang

  DOI：10.1016/j.bmc.2020.115354

  日期：2020.3

  A series of anthranilamide derivatives were designed and synthesized as novel smoothened (SMO) inhibitors based on the SMO inhibitor taladegib (LY2940680), which can also inhibit the SMO-D473H mutant, via a ring-opening strategy. The phthalazine core in LY2940680 was replaced with anthranilamide, which retained the inhibitory activity towards the hedgehog (Hh) signaling pathway as evidenced by a dual

  设计并合成了一系列邻氨基苯甲酰胺衍生物，作为基于SMO抑制剂taladegib（LY2940680）的新型平滑（SMO）抑制剂，后者也可以通过开环策略抑制SMO-D473H突变体。LY2940680中的酞嗪核心被蒽环酰胺取代，后者通过双重萤光素酶报告基因检测证实了对刺猬（Hh）信号通路的抑制活性。化合物12a对Hh信号通路表现出最佳的抑制活性，IC50值为34.09 nM，并且对Daoy细胞系的增殖抑制活性（IC50 = 0.48μM）比LY2940680（IC50 = 0.79μM）好。
• Discovery and structure–activity relationship of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a new series of potent apoptosis inducers
  作者：Han-Zhong Zhang、Gisela Claassen、Candace Crogran-Grundy、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1016/j.bmc.2007.09.046

  日期：2008.1

  We report the discovery and SAR study of a series of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as potent inducers of apoptosis. N-(3-Acetylphenyl)-2,3-dihydro-1H-cyclopenta[b]quinolin-9-amine (2) was discovered through our cell- and caspase-based HTS assays as an inducer of apoptosis. Compound 2 is active against cancer cells derived from several human solid tumors, with EC50 values ranging from 400 to 700 nM. SAR study of hit 2 led to the discovery of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a novel series of potent apoptosis inducers, with 1,3-dimethyl-N-(4-propionylphenyl)-1H-pyrazolo[3,4-b]quinotin-amine (6b) having EC50 values ranging from 30 to 70 nM in cancer cells. These compounds also demonstrated potent activity in the cell growth inhibition assay, with GI(50) values of 16-42 nM for compound 6b. (C) 2007 Elsevier Ltd. All rights reserved.