2-amino-4-[4-(tert-butoxycarbonyl)-2-(S)-methylpiperazin-1-yl]-6-chloropyrimidine-5-carboxaldehyde | 1423165-41-6

• 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: 2-amino-4-[4-(tert-butoxycarbonyl)-2-(S)-methylpiperazin-1-yl]-6-chloropyrimidine-5-carboxaldehyde
• 英文别名: 2-amino-6-chloro-4-[2-(S)-methyl-4-(tert-butoxycarbonyl)piperazin-1-yl]pyrimidine-5-carbaldehyde；tert-butyl (3S)-4-(2-amino-6-chloro-5-formyl-pyrimidin-4-yl)-3-methyl-piperazine-1-carboxylate；tert-butyl (3S)-4-(2-amino-6-chloro-5-formylpyrimidin-4-yl)-3-methylpiperazine-1-carboxylate
• CAS: 1423165-41-6
• 化学式: C₁₅H₂₂ClN₅O₃
• 分子量: 355.824
• InChiKey: DWBHVVHGWFUUAV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  101.65
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-amino-4-[4-(tert-butoxycarbonyl)-2-(S)-methylpiperazin-1-yl]-6-chloropyrimidine-5-carboxaldehyde 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 6-amino-4-[2-(S)-methylpiperazin-1-yl]-1-methylpyrazolo[3,4-d]pyrimidine dihydrochloride
  参考文献：
  名称：

  [EN] THERAPEUTICALLY ACTIVE PYRAZOLO-PYRIMIDINE DERIVATIVES
  [FR] DÉRIVÉS DE PYRAZOLO-PYRIMIDINE THÉRAPEUTIQUEMENT ACTIFS

  摘要：

  一系列在4-位被一种二氮杂单环、桥接的双环或螺环基团取代的吡唑并[3,4-d]嘧啶衍生物，在治疗和/或预防各种人类疾病方面具有益处，包括炎症、自身免疫和肿瘤性疾病；病毒性疾病和疟疾；以及器官和细胞移植排斥。

  公开号：

  WO2014096423A1
• 作为产物：
  描述：

  2-氨基-4,6-二氯嘧啶-5-甲醛 、 (S)-4-N-叔丁氧羰基-2-甲基哌嗪 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以94%的产率得到2-amino-4-[4-(tert-butoxycarbonyl)-2-(S)-methylpiperazin-1-yl]-6-chloropyrimidine-5-carboxaldehyde
  参考文献：
  名称：

  [EN] THERAPEUTICALLY ACTIVE PYRAZOLO-PYRIMIDINE DERIVATIVES
  [FR] DÉRIVÉS DE PYRAZOLO-PYRIMIDINE THÉRAPEUTIQUEMENT ACTIFS

  摘要：

  一系列在4-位被一种二氮杂单环、桥接的双环或螺环基团取代的吡唑并[3,4-d]嘧啶衍生物，在治疗和/或预防各种人类疾病方面具有益处，包括炎症、自身免疫和肿瘤性疾病；病毒性疾病和疟疾；以及器官和细胞移植排斥。

  公开号：

  WO2014096423A1

文献信息

• Therapeutically Active Fused Pyrimidine Derivatives
  申请人：Brookings Daniel Christopher

  公开号：US20140309222A1

  公开（公告）日：2014-10-16

  A series of monocyclic or bicyclic diamine-substituted thieno[2,3-d]pyrimidine and isothiazolo[5,4-d]pyrimidine derivatives are beneficial in the treatment and/or prevention of various human ailments, including inflammatory, autoimmune and oncological disorders; viral diseases; and organ and cell transplant rejection.

  一系列单环或双环二胺取代的噻吩[2,3-d]嘧啶和异噻唑[5,4-d]嘧啶衍生物在治疗和/或预防各种人类疾病方面具有益处，包括炎症性、自身免疫和肿瘤性疾病；病毒性疾病；以及器官和细胞移植排斥。
• Therapeutically Active Pyrazolo-Pyrimidine Derivatives
  申请人：UCB PHARMA S.A.

  公开号：US20160194329A1

  公开（公告）日：2016-07-07

  A series of pyrazolo[3,4-d]pyrimidine derivatives that are substituted at the 4-position by a diaza monocyclic, bridged bicyclic or spirocyclic moiety, are beneficial in the treatment and/or prevention of various human ailments, including inflammatory, autoimmune and oncological disorders; viral diseases and malaria; and organ and cell transplant rejection.

  一系列在4位点取代了含有一环氮杂原子的单环、桥环或螺环的嘧唑并[3,4-d]嘧啶衍生物，在治疗和/或预防各种人类疾病方面具有益处，包括炎症、自身免疫和肿瘤性疾病；病毒性疾病和疟疾；以及器官和细胞移植排斥反应。
• 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.
• THERAPEUTICALLY ACTIVE PYRAZOLO-PYRIMIDINE DERIVATIVES
  申请人：UCB Biopharma SPRL

  公开号：EP2935269B1

  公开（公告）日：2018-04-11
• US9227984B2
  申请人：——

  公开号：US9227984B2

  公开（公告）日：2016-01-05