2-甲基-3-(1H-吡唑-1-基)丙酸 | 197094-12-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-甲基-3-(1H-吡唑-1-基)丙酸
• 中文别名: 2-甲基-3-吡唑-1-基-丙酸
• 英文名称: 2-methyl-3-(1H-pyrazol-1-yl)propanoic acid
• 英文别名: 2-methyl-3-pyrazol-1-ylpropanoic acid
• CAS: 197094-12-5
• 化学式: C₇H₁₀N₂O₂
• mdl: MFCD07643180
• 分子量: 154.169
• InChiKey: FWIFKSTVTRTEQU-UHFFFAOYSA-N

物化性质

• 沸点：
  310.2±25.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-3-(1H-吡唑-1-基)丙酸 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以30%的产率得到5-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-4-one
  参考文献：
  名称：

  Chemical Compounds

  摘要：

  提供了一系列新颖的吡啶或嘧啶衍生物，可以抑制CDK9，并可能对治疗过度增殖性疾病有用。特别是这些化合物在治疗增殖性疾病方面具有用途，如癌症，包括血液恶性肿瘤，如急性髓细胞白血病，多发性骨髓瘤，慢性淋巴细胞白血病，弥漫性大B细胞淋巴瘤，Burkitt淋巴瘤，滤泡性淋巴瘤以及实体肿瘤，如乳腺癌，肺癌，神经母细胞瘤和结肠癌。

  公开号：

  US20160376287A1
• 作为产物：
  描述：

  ethyl 2-methyl-3-(1H-pyrazol-1-yl)propanoate 在 sodium hydroxide 作用下， 反应 20.0h， 生成 2-甲基-3-(1H-吡唑-1-基)丙酸
  参考文献：
  名称：

  Novel Parham-type Cycloacylations of 1H-Pyrazole-1-alkanoic Acids

  摘要：

  将 1H-吡唑-1-烷酸与两当量的正丁基锂接触，通过帕勒姆式环化过程生成相应的环酮。虽然产量不高，但这一过程代表了一种简单直接的非亲核吡唑碳分子内酰化反应。

  DOI：

  10.1055/s-1997-955

文献信息

• [EN] PHARMACEUTICAL COMPOUNDS<br/>[FR] COMPOSÉS PHARMACEUTIQUES
  申请人：ALMAC DISCOVERY LTD

  公开号：WO2018020242A1

  公开（公告）日：2018-02-01

  The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.

  本发明涉及一种具有以下式（I）的化合物，该化合物可用作泛素特异性蛋白酶USP19活性的抑制剂。本发明还涉及包含这些化合物的药物组合物以及使用这些化合物进行治疗的方法。
• Chemical compounds
  申请人：ASTRAZENECA AB

  公开号：US10717746B2

  公开（公告）日：2020-07-21

  Provided are a series of novel pyridine or pyrimidine derivatives which inhibit CDK9 and may be useful for the treatment of hyperproliferative diseases. In particular the compounds are of use in the treatment of proliferative disease such as cancer including hematological malignancies such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt's lymphoma, follicular lymphoma and solid tumors such as breast cancer, lung cancer, neuroblastoma and colon cancer.

  本研究提供了一系列新型吡啶或嘧啶衍生物，它们能抑制 CDK9，可用于治疗增殖过快的疾病。特别是这些化合物可用于治疗增殖性疾病，如癌症，包括血液恶性肿瘤，如急性髓性白血病、多发性骨髓瘤、慢性淋巴细胞白血病、弥漫性大 B 细胞淋巴瘤、伯基特淋巴瘤、滤泡性淋巴瘤和实体瘤，如乳腺癌、肺癌、神经母细胞瘤和结肠癌。
• Pharmaceutical compounds
  申请人：ALMAC DISCOVERY LIMITED

  公开号：US11053213B2

  公开（公告）日：2021-07-06

  The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.

  本发明涉及可用作泛素特异性蛋白酶 USP19 活性抑制剂的式 (I) 化合物。本发明还涉及包含这些化合物的药物组合物以及将这些化合物用于治疗的方法。
• Pyridine and pyrimidine derivatives
  申请人：ASTRAZENECA AB

  公开号：US11352369B2

  公开（公告）日：2022-06-07

  Provided are a series of novel pyridine or pyrimidine derivatives which inhibit CDK9 and may be useful for the treatment of hyperproliferative diseases. In particular the compounds are of use in the treatment of proliferative disease such as cancer including hematological malignancies such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt's lymphoma, follicular lymphoma and solid tumors such as breast cancer, lung cancer, neuroblastoma and colon cancer.

  本研究提供了一系列新型吡啶或嘧啶衍生物，它们能抑制 CDK9，可用于治疗增殖过快的疾病。特别是这些化合物可用于治疗增殖性疾病，如癌症，包括血液恶性肿瘤，如急性髓性白血病、多发性骨髓瘤、慢性淋巴细胞白血病、弥漫性大 B 细胞淋巴瘤、伯基特淋巴瘤、滤泡性淋巴瘤和实体瘤，如乳腺癌、肺癌、神经母细胞瘤和结肠癌。
• Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies
  作者：Bernard Barlaam、Robert Casella、Justin Cidado、Calum Cook、Chris De Savi、Allan Dishington、Craig S. Donald、Lisa Drew、Andrew D. Ferguson、Douglas Ferguson、Steve Glossop、Tyler Grebe、Chungang Gu、Sudhir Hande、Janet Hawkins、Alexander W. Hird、Jane Holmes、James Horstick、Yun Jiang、Michelle L. Lamb、Thomas M. McGuire、Jane E. Moore、Nichole O’Connell、Andy Pike、Kurt G. Pike、Theresa Proia、Bryan Roberts、Maryann San Martin、Ujjal Sarkar、Wenlin Shao、Darren Stead、Neil Sumner、Kumar Thakur、Melissa M. Vasbinder、Jeffrey G. Varnes、Jianyan Wang、Lei Wang、Dedong Wu、Liangwei Wu、Bin Yang、Tieguang Yao

  DOI：10.1021/acs.jmedchem.0c01754

  日期：2020.12.24

  A CDK9 inhibitor having short target engagement would enable a reduction of Mcl-1 activity, resulting in apoptosis in cancer cells dependent on Mcl-1 for survival. We report the optimization of a series of amidopyridines (from compound 2), focusing on properties suitable for achieving short target engagement after intravenous administration. By increasing potency and human metabolic clearance, we identified compound 24, a potent and selective CDK9 inhibitor with suitable predicted human pharmacokinetic properties to deliver transient inhibition of CDK9. Furthermore, the solubility of 24 was considered adequate to allow i.v. formulation at the anticipated effective dose. Short-term treatment with compound 24 led to a rapid dose- and time-dependent decrease of pSer2-RNAP2 and Mcl-1, resulting in cell apoptosis in multiple hematological cancer cell lines. Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematological tumors. Compound 24 is currently in clinical trials for the treatment of hematological malignancies.