phenyl N-(6-methoxy-2-methylpyridin-3-yl)carbamate | 1616415-52-1

• 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: phenyl N-(6-methoxy-2-methylpyridin-3-yl)carbamate
• 英文别名: Phenyl N-(6-methoxy-2-methylpyridin-3-yl)carbamate
• CAS: 1616415-52-1
• 化学式: C₁₄H₁₄N₂O₃
• 分子量: 258.277
• InChiKey: VRYIETYQLQNXQM-UHFFFAOYSA-N

物化性质

• 沸点：
  359.8±42.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  phenyl N-(6-methoxy-2-methylpyridin-3-yl)carbamate 、 4-[(2S)-2-ethylpiperazin-1-yl]-1-methylpyrazolo[3,4-d]pyrimidin-6-amine dihydrochloride 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 以80%的产率得到(3S)-4-(6-amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-ethyl-N-(6-methoxy-2-methylpyridin-3-yl)piperazine-1-carboxamide
  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：

  5-氨基-2-甲氧基-6-甲基嘧啶 、 氯甲酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以56%的产率得到phenyl N-(6-methoxy-2-methylpyridin-3-yl)carbamate
  参考文献：
  名称：

  PYRIDAZINONE-AMIDES DERIVATIVES

  摘要：

  本发明涉及公式（I）中R1、Ra、Rb和Z具有claim1中给定的含义的化合物，以及它们在预防和治疗疾病中的用途。

  公开号：

  US20150376167A1

文献信息

• [EN] FUSED BICYCLIC HETEROAROMATIC DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS HÉTÉROAROMATIQUES BICYCLIQUES CONDENSÉS UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：UCB BIOPHARMA SPRL

  公开号：WO2015193169A1

  公开（公告）日：2015-12-23

  A series of fused bicyclic heteroaromatic derivatives of formula (I), as defined herein, being selective inhibitors of phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) activity, 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.

  一系列融合的双环杂芳衍生物，其化学式为（I），如本文所定义，是选择性抑制磷脂酰肌醇-4-激酶IIIβ（PI4KIIIβ）活性的药物，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；病毒性疾病和疟疾；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。
• Fused bicyclic heteroaromatic derivatives as kinase inhibitors
  申请人：UCB Biopharma SPRL

  公开号：US10000497B2

  公开（公告）日：2018-06-19

  A series of fused bicyclic heteroaromatic derivatives of formula (I), as defined herein, being selective inhibitors of phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) activity, 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.

  一系列如本文所定义的式(I)的融合双环杂芳香族衍生物是磷脂酰肌醇-4-激酶 IIIβ (PI4KIIIβ)活性的选择性抑制剂，有利于治疗和/或预防人类的各种疾病，包括炎症、自身免疫和肿瘤疾病；病毒性疾病和疟疾；以及器官和细胞移植排斥反应。
• Pyrazolo-pyridine derivatives as kinase inhibitors
  申请人：UCB Biopharma SPRL

  公开号：US10087180B2

  公开（公告）日：2018-10-02

  A series of pyrazolo[3,4-b]pyridine derivatives that are substituted at the 4-position by a diaza monocyclic, bridged bicyclic or spirocyclic moiety, being selective inhibitors of phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) activity, 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.

  一系列吡唑并[3,4-b]吡啶衍生物在 4 位被重氮单环、桥接双环或螺环分子取代，是磷脂酰肌醇-4-激酶 IIIβ (PI4KIIIβ) 活性的选择性抑制剂，有利于治疗和/或预防各种人类疾病，包括炎症、自身免疫性疾病和肿瘤疾病、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.