2,3-di-[(benzyloxycarbonyl)amino]-1-chloropropan | 119244-95-0

• 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: 2,3-di-[(benzyloxycarbonyl)amino]-1-chloropropan
• 英文别名: benzyl N-[1-chloro-3-(phenylmethoxycarbonylamino)propan-2-yl]carbamate
• CAS: 119244-95-0
• 化学式: C₁₉H₂₁ClN₂O₄
• 分子量: 376.84
• InChiKey: SAOWIWLXWAXJDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3-di-[(benzyloxycarbonyl)amino]-1-chloropropan 在 溶剂黄146 作用下， 生成 1.2-Diamino-3-chlorpropan
  参考文献：
  名称：

  Synthesis of three substituted aminochloropropanes

  摘要：

  DOI：

  10.1021/jo00899a036
• 作为产物：
  描述：

  methanesulfonic acid 2-benzyloxycarbonylamino-1-(benzyloxycarbonylaminomethyl)-ethyl ester 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 paraffin 为溶剂， 反应 0.5h， 生成 2,3-di-[(benzyloxycarbonyl)amino]-1-chloropropan
  参考文献：
  名称：

  Convenient synthesis of vicinal diamines

  摘要：

  DOI：

  10.1021/jo00269a036

文献信息

• [EN] 5-ALKYLTHIO-7-[(4-ARYLBENZYL)AMINO]-1(2)H-PYRAZOLO[4,3-D]PYRIMIDINES FOR TREATMENT OF LYMPHOMA<br/>[FR] 5-ALKYLTHIO-7-[(4-ARYLBENZYL) AMINO] -1 (2) H-PYRAZOLO [4,3-D] PYRIMIDINES POUR LE TRAITEMENT DU LYMPHOME
  申请人：UNIV PALACKEHO

  公开号：WO2019149295A1

  公开（公告）日：2019-08-08

  The present invention relates to 5-alkylthio-7-[(4-arylbenzyl)amino]-1(2)H-pyrazolo[4,3-d]pyrimidine derivatives of formula I which are effective inhibitors of kinases and exhibit strong antiproliferative and proapoptotic properties on lymphoma cells. This invention further relates to use of said derivatives in the treatment of blood hyperproliferative diseases, such as Non-Hodgkin lymphomas.

  本发明涉及式I的5-烷基硫基-7-[(4-芳基苄基)氨基]-1(2)H-吡唑并[4,3-d]嘧啶衍生物，它们是激酶的有效抑制剂，并在淋巴瘤细胞上表现出强烈的抗增殖和促凋亡特性。本发明还涉及利用这些衍生物治疗血液过度增殖性疾病，如非霍奇金淋巴瘤。
• 3,5,7-Substituted Pyrazolo[4,3-<i>d</i>]Pyrimidine Inhibitors of Cyclin-Dependent Kinases and Cyclin K Degraders
  作者：Radek Jorda、Libor Havlíček、Miroslav Peřina、Veronika Vojáčková、Tomáš Pospíšil、Stefan Djukic、Jana Škerlová、Jiří Grúz、Nicol Renešová、Pavel Klener、Pavlína Řezáčová、Miroslav Strnad、Vladimír Kryštof

  DOI：10.1021/acs.jmedchem.1c02184

  日期：2022.7.14

  -7-[4-(pyrazol-1-yl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidine (24) at 1.7 Å resolution, confirming the competitive mode of inhibition. Biochemical and cellular assays in lymphoma cell lines confirmed the expected mechanism of action through dephosphorylation of retinoblastoma protein and RNA polymerase II, leading to induction of apoptosis. Importantly, we also revealed an interesting ability of

  3,5,7-三取代的吡唑并[4,3- d ]嘧啶已被确定为细胞周期蛋白依赖性激酶 (CDK) 的有效抑制剂，CDK 是既定的药物靶点。在此，我们描述了它们进一步的结构修饰，从而产生具有强抗增殖活性的新型纳摩尔抑制剂。我们用 5-(2-amino-1-ethyl)thio-3-cyclobutyl-7-[4-(pyrazol-1-yl)benzyl]amino-1(2) H确定了完全活性 CDK2/A2 的晶体结构-吡唑并[4,3- d ]嘧啶（24) 在 1.7 Å 分辨率下，确认抑制的竞争模式。淋巴瘤细胞系中的生化和细胞分析证实了预期的作用机制，即通过视网膜母细胞瘤蛋白和 RNA 聚合酶 II 的去磷酸化，从而诱导细胞凋亡。重要的是，我们还揭示了化合物24在体外和体内源自患者的异种移植物中诱导蛋白酶体依赖性细胞周期蛋白 K 降解的有趣能力。我们提出24具有双重作用机制，既作为激酶抑制剂，又作为分子胶诱导
• 5-alkylthio-7-[(4-arylbenzyl)amino]-1(2)H-pyrazolo[4,3-d]pyrimidines for treatment of lymphoma
  申请人：UNIVERZITA PALACKEHO V OLOMOUCI

  公开号：US11186583B2

  公开（公告）日：2021-11-30

  5-alkylthio-7-[(4-arylbenzyl)amino]-1(2)H-pyrazolo[4,3-d]pyrimidine derivatives of formula I that are effective inhibitors of kinases and exhibit strong antiproliferative and proapoptotic properties on lymphoma cells. Derivatives in the treatment of blood hyperproliferative diseases, such as Non-Hodgkin lymphomas are also disclosed.

  式 I 的 5-烷基硫基-7-[(4-芳基苄基)氨基]-1(2)H-吡唑并[4,3-d]嘧啶衍生物是有效的激酶抑制剂，对淋巴瘤细胞具有很强的抗增殖和促凋亡特性。此外，还公开了用于治疗血液增生性疾病（如非霍奇金淋巴瘤）的衍生物。
• 3,5,7-Substituted Pyrazolo[4,3-<i>d</i>]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models
  作者：Radek Jorda、Libor Havlíček、Antonín Šturc、Diana Tušková、Lenka Daumová、Mahmudul Alam、Jana Škerlová、Michaela Nekardová、Miroslav Peřina、Tomáš Pospíšil、Jitka Široká、Lubor Urbánek、Petr Pachl、Pavlína Řezáčová、Miroslav Strnad、Pavel Klener、Vladimír Kryštof

  DOI：10.1021/acs.jmedchem.9b00189

  日期：2019.5.9

  Cyclin-dependent kinases are therapeutic targets frequently deregulated in various cancers. By convenient alkylation of the 5-sulfanyl group, we synthesized 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines with various substitutions at position 5 with potent antiproliferative activity in non-Hodgkin lymphoma cell lines. The most potent derivative 4.35 also displayed activities across more than 60 cancer cell lines. The kinase profiling confirmed high selectivity of 4.35 toward cyclin-dependent kinases (CDKs) 2, 5, and 9, and the cocrystal with CDK2/cyclin A2 revealed its binding in the active site. Cultured lymphoma cell lines treated with 4.35 showed dephosphorylation of CDK substrates, cleavage of PARP-1, downregulation of XIAP and MCL-1, and activation of caspases, which collectively confirmed ongoing apoptosis. Moreover, 4.35 demonstrated significant activity in various cell line xenograft and patient-derived xenograft mouse models in vivo both as a monotherapy and as a combination therapy with the BCL2-targeting venetoclax. These findings support further studies of combinatorial treatment based on CDK inhibitors.
• JONES, DAVID S.;SRINIVASAN, ANANTHACHARI;KASINA, SUDHAKAR;FRITZBERG, ALAN+, J. ORG. CHEM., 54,(1989) N, C. 1940-1943
  作者：JONES, DAVID S.、SRINIVASAN, ANANTHACHARI、KASINA, SUDHAKAR、FRITZBERG, ALAN+

  DOI：——

  日期：——