tert-butyl 4-[5-amino-2-(3-pyridyl)thiazolo[5,4-d]pyrimidin-7-yl]piperazine-1-carboxylate | 1262121-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-[5-amino-2-(3-pyridyl)thiazolo[5,4-d]pyrimidin-7-yl]piperazine-1-carboxylate
• 英文别名: tert-butyl 4-(5-amino-2-(pyridin-3-yl)thiazolo[5,4-d]pyrimidin-7-yl)piperazine-1-carboxylate；tert-butyl 4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)piperazine-1-carboxylate
• CAS: 1262121-06-1
• 化学式: C₁₉H₂₃N₇O₂S
• 分子量: 413.503
• InChiKey: YWVMMUGIJJLXOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[5-amino-2-(3-pyridyl)thiazolo[5,4-d]pyrimidin-7-yl]piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 4-[5-氨基-2-(吡啶-3-基)噻唑并[5,4-d]嘧啶-7-基]-N-(对甲苯基)哌嗪-1-甲酰胺
  参考文献：
  名称：

  ANTI-CANCER ACTIVITY OF NOVEL BICYCLIC HETEROCYCLES

  摘要：

  本发明涉及式I、II、III或IV的化合物，和/或其药用可接受的加合物盐和/或其立体异构体和/或其溶剂化合物，式(I)、(II)、(III)和(IV)中R1、R2、R3、R4、R5、R6、R7、R8、R9、R11和R12如权利要求书中所定义或在发明说明书中详细描述的那样，以及使用所述化合物来治疗或预防增殖性疾病以及用于制造治疗或预防增殖性疾病的药物，特别是像白血病这样的癌症。本发明还涉及所述化合物的药物组合物以及使用所述药物组合物来治疗或预防增殖性疾病。本发明还涉及将所述化合物用作生物活性成分，更具体地用作治疗增殖性疾病和病理状况的药物，例如癌症如白血病等。

  公开号：

  US20140088088A1
• 作为产物：
  描述：

  tert-butyl 4-(2,5-diamino-6-chloropyrimidin-4-yl)piperazine-1-carboxylate 在 sodiumsulfide nonahydrate 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 tert-butyl 4-[5-amino-2-(3-pyridyl)thiazolo[5,4-d]pyrimidin-7-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  ANTI-CANCER ACTIVITY OF NOVEL BICYCLIC HETEROCYCLES

  摘要：

  本发明涉及式I、II、III或IV的化合物，和/或其药用可接受的加合物盐和/或其立体异构体和/或其溶剂化合物，式(I)、(II)、(III)和(IV)中R1、R2、R3、R4、R5、R6、R7、R8、R9、R11和R12如权利要求书中所定义或在发明说明书中详细描述的那样，以及使用所述化合物来治疗或预防增殖性疾病以及用于制造治疗或预防增殖性疾病的药物，特别是像白血病这样的癌症。本发明还涉及所述化合物的药物组合物以及使用所述药物组合物来治疗或预防增殖性疾病。本发明还涉及将所述化合物用作生物活性成分，更具体地用作治疗增殖性疾病和病理状况的药物，例如癌症如白血病等。

  公开号：

  US20140088088A1

文献信息

• Discovery of 7-<i>N</i>-Piperazinylthiazolo[5,4-<i>d</i>]pyrimidine Analogues as a Novel Class of Immunosuppressive Agents with in Vivo Biological Activity
  作者：Mi-Yeon Jang、Yuan Lin、Steven De Jonghe、Ling-Jie Gao、Bart Vanderhoydonck、Mathy Froeyen、Jef Rozenski、Jean Herman、Thierry Louat、Kristien Van Belle、Mark Waer、Piet Herdewijn

  DOI：10.1021/jm101254z

  日期：2011.1.27

  Herein we describe the synthesis and in vitro and in vivo activity of thiazolo[5,4-d]pyrimidines as a novel class of immunosuppressive agents, useful for preventing graft rejection after organ transplantation. This research resulted in the discovery of a series of compounds with potent activity in the mixed lymphocyte reaction (MLR) assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. The most potent congeners displayed IC50 values of less than 50 nM in this MLR assay and hence are equipotent to cyclosporin A, a clinically used immunosuppressive drug. One representative of this series was further evaluated in a preclinical animal model of organ transplantation and showed excellent in vivo efficacy. It validates these compounds as new promising immunosuppressive drugs.
• Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment <i>in Vivo</i>
  作者：James Reuberson、Helen Horsley、Richard J. Franklin、Daniel Ford、Judi Neuss、Daniel Brookings、Qiuya Huang、Bart Vanderhoydonck、Ling-Jie Gao、Mi-Yeon Jang、Piet Herdewijn、Anant Ghawalkar、Farnaz Fallah-Arani、Adnan R. Khan、Jamie Henshall、Mark Jairaj、Sarah Malcolm、Eleanor Ward、Lindsay Shuttleworth、Yuan Lin、Shengqiao Li、Thierry Louat、Mark Waer、Jean Herman、Andrew Payne、Tom Ceska、Carl Doyle、Will Pitt、Mark Calmiano、Martin Augustin、Stefan Steinbacher、Alfred Lammens、Rodger Allen

  DOI：10.1021/acs.jmedchem.8b00521

  日期：2018.8.9

  The primary target of a novel series of immunosuppressive 7-piperazin-1-ylthiazolo[5,4-d]pyrimidin-5-amines was identified as the lipid kinase, PI4KIII beta. Evaluation of the series highlighted their poor solubility and unwanted off-target activities. A medicinal chemistry strategy was put in place to optimize physicochemical properties within the series, while maintaining potency and improving selectivity over other lipid kinases. Compound 22 was initially identified and profiled in vivo, before further modifications led to the discovery of 44 (UCB9608), a vastly more soluble, selective compound with improved metabolic stability and excellent pharmacokinetic profile. A co-crystal structure of 44 with PI4KIII beta was solved, confirming the binding mode of this class of inhibitor. The much-improved in vivo profile of 44 positions it as an ideal tool compound to further establish the link between PI4KIII beta inhibition and prolonged allogeneic organ engraftment, and suppression of immune responses in vivo.
• ANTI-CANCER ACTIVITY OF NOVEL BICYCLIC HETEROCYCLES
  申请人：Herman Jean

  公开号：US20140088088A1

  公开（公告）日：2014-03-27

  The present invention relates to compound of formula I, II, III, or IV, and/or a pharmaceutical acceptable addition salt thereof and/or a stereoisomer thereof and/or a solvate thereof, Formulas (I), (II), (III) and (IV) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , and R 12 are as defined in the claim 1 or as described in detail in the description of the invention, and to the use of said compounds to treat or prevent proliferative disorders and their use to manufacture a medicine to treat or prevent proliferative disorders, particularly cancer such as leukemia. The present invention also relates to pharmaceutical compositions of said compounds and the use of said pharmaceutical compositions to treat or prevent proliferative disorders. The present invention further relates to the use of said compounds as biologically active ingredients, more specifically as medicaments for the treatment of proliferative disorders and pathologic conditions such as, but not limited to, cancer such as leukemia.

  本发明涉及式I、II、III或IV的化合物，和/或其药用可接受的加合物盐和/或其立体异构体和/或其溶剂化合物，式(I)、(II)、(III)和(IV)中R1、R2、R3、R4、R5、R6、R7、R8、R9、R11和R12如权利要求书中所定义或在发明说明书中详细描述的那样，以及使用所述化合物来治疗或预防增殖性疾病以及用于制造治疗或预防增殖性疾病的药物，特别是像白血病这样的癌症。本发明还涉及所述化合物的药物组合物以及使用所述药物组合物来治疗或预防增殖性疾病。本发明还涉及将所述化合物用作生物活性成分，更具体地用作治疗增殖性疾病和病理状况的药物，例如癌症如白血病等。