3-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine | 1955523-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine
• 英文别名: 3-iodo-4H,5H,6H,7H-pyrazolo[1,5-a]pyrimidine
• CAS: 1955523-82-6
• 化学式: C₆H₈IN₃
• 分子量: 249.054
• InChiKey: VBPMBLKWANECPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine 在 盐酸 、 甲醇 、 potassium phosphate 、 isopropyl magnesium lithium chloride 、 XPhos Pd G2 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 38.0h， 生成 (1S,3R)-3-amino-N-(5-chloro-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-yl)cyclohexanecarboxamide trihydrochloride
  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：

  4,5,6,7-四氢吡唑并[1,5-A]嘧啶 在 N-碘代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以28.9%的产率得到3-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine
  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

文献信息

• [EN] POLYCYCLIC AMIDE DERIVATIVES AS CDK9 INHIBITORS<br/>[FR] DÉRIVÉS D'AMIDES POLYCYCLIQUES COMME INHIBITEURS DE LA CDK9
  申请人：ASTRAZENECA AB

  公开号：WO2017001354A1

  公开（公告）日：2017-01-05

  Provided are a series of novel pyridine or pyrimidine derivatives of Formula (I) 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 diseases 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. A is C(R5) or N; R5 is H, C1-3alkyl, CN or halogen; R2 is optionally substituted 3-7 membered heterocycloalkyl or 3-7 membered cycloalkyl; R4 is (A) or (B) wherein X and Y together with the atoms to which they are attached form an optionally substituted, saturated or partially saturated 5 to 7 membered heterocycloalkyl ring which, in addition to the bridge nitrogen, may contain one or two heteroatoms selected from N, O, and S; J is N or CR11; and R11 is H or C1-3alkyl.

  提供了一系列新型的吡啶或嘧啶衍生物，其化学式为（I），可以抑制CDK9，并可能用于治疗过度增殖性疾病。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。其中，A是C（R5）或N；R5是H，C1-3烷基，CN或卤素；R2是可选择的取代的3-7成员杂环烷基或3-7成员环烷基；R4是（A）或（B），其中X和Y与它们连接的原子一起形成一个可选择的取代的，饱和或部分饱和的5到7成员杂环烷基环，除了桥氮外，可能包含一个或两个从N，O和S中选择的杂原子；J是N或CR11；R11是H或C1-3烷基。
• 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。
• 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.
• POLYCYCLIC AMIDE DERIVATIVES AS CDK9 INHIBITORS
  申请人：Astrazeneca AB

  公开号：EP3313838B1

  公开（公告）日：2019-04-03