methyl 5-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propyl]oxy}nicotinate | 1055968-95-0

• 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: methyl 5-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propyl]oxy}nicotinate
• 英文别名: methyl 5-[(2R)-3-(4-fluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propoxy]pyridine-3-carboxylate
• CAS: 1055968-95-0
• 化学式: C₂₁H₂₅FN₂O₅
• 分子量: 404.438
• InChiKey: ZCJYGPWBJSNKKJ-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-4-methyl-3-cyanoquinoline 、 methyl 5-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propyl]oxy}nicotinate 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 tert-butyl N-[(2R)-1-[5-[2-(3-cyano-6,7-dimethoxyquinolin-4-yl)acetyl]pyridin-3-yl]oxy-3-(4-fluorophenyl)propan-2-yl]carbamate
  参考文献：
  名称：

  The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1)

  摘要：

  A series of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c] [2,7]naphthyridin-4-ylamine-based inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1) has been identified. Several examples appear to be potent and relatively selective inhibitors of PDK-1 over the related AGC kinases PKA, PKB/AKT, and p70S6K. The introduction of a stereochemical center beside the amino substituent on the aminoalkoxy-side chain had little effect upon the inhibitory activity against these enzymes, and X-ray crystallographic analyses of a representative pair of enantiomeric inhibitors bound to the active site of PDK-1 revealed comparable binding modes for each enantiomer. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.12.036
• 作为产物：
  描述：

  N-((1R)-1-[(4-fluorophenyl)methyl]-2-hydroxyethyl)(tert-butoxy)carboxamide 、 5-羟基烟酸甲酯 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 3.17h， 生成 methyl 5-{[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(4-fluorophenyl)propyl]oxy}nicotinate
  参考文献：
  名称：

  The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1)

  摘要：

  A series of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c] [2,7]naphthyridin-4-ylamine-based inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1) has been identified. Several examples appear to be potent and relatively selective inhibitors of PDK-1 over the related AGC kinases PKA, PKB/AKT, and p70S6K. The introduction of a stereochemical center beside the amino substituent on the aminoalkoxy-side chain had little effect upon the inhibitory activity against these enzymes, and X-ray crystallographic analyses of a representative pair of enantiomeric inhibitors bound to the active site of PDK-1 revealed comparable binding modes for each enantiomer. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.12.036

文献信息

• Benzo[C][2,7]Naphtyridine Derivatives, Methods of Making Thereof and Methods of Use Thereof
  申请人：WISSNER Allan

  公开号：US20080293712A1

  公开（公告）日：2008-11-27

  The present invention relates to Benzo[c][2,7]naphthyridine Derivatives, compositions comprising an effective amount of a Benzo[c][2,7]naphthyridine Derivative, methods for treating or preventing a proliferative disorder or an autoimmune disease, comprising administering to a subject in need thereof an effective amount of a Benzo[c][2,7]naphthyridine Derivative, methods for modulating PDK-1 activity, PKA activity, Akt activity, S6K activity, or PKC activity, comprising administering to a subject in need thereof an effective amount of a Benzo[c][2,7]naphthyridine Derivative. The invention also relates to processes for preparing a Benzo[c][2,7]naphthyridine Derivative.

  本发明涉及苯并[c][2,7]萘啉衍生物，包含有效量苯并[c][2,7]萘啉衍生物的组合物，用于治疗或预防增殖性疾病或自身免疫疾病的方法，包括向需要治疗的受体内给予有效量的苯并[c][2,7]萘啉衍生物，用于调节PDK-1活性、PKA活性、Akt活性、S6K活性或PKC活性的方法，包括向需要治疗的受体内给予有效量的苯并[c][2,7]萘啉衍生物。本发明还涉及制备苯并[c][2,7]萘啉衍生物的过程。
• [EN] BENZO[C][2,7]NAPHTHYRIDINE DERIVATIVES, AND THEIR USE AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE BENZO[C][2,7]NAPHTYRIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE
  申请人：WYETH CORP

  公开号：WO2008109613A1

  公开（公告）日：2008-09-12

  [EN] The present invention relates to Benzo[c] [2,7] naph thy ri dine Derivatives of formula (I), compositions comprising an effective amount of a Benzo[c] [2,7]naphthyridine Derivative, methods for treating or preventing a proliferative disorder or an autoimmune disease, comprising administering to a subject in need thereof an effective amount of a Benzo[c] [2,7]naphthyridine Derivative, methods for modulating PDK-I activity, PKA activity, Akt activity, S6K activity, or PKC activity, comprising administering to a subject in need thereof an effective amount of a Benzo[c] [2,7] naphthyridine Derivative. The invention also relates to processes for preparing a Benzo[c] [2,7] naphthyridine Derivative.
  [FR] L'invention concerne des dérivés de benzo[c][2,7]naphtyridine représentés par la formule (I), des compositions comprenant une quantité efficace de benzo[c][2,7]naphtyridine, des procédés pour le traitement ou la prévention d'un trouble prolifératif ou d'une maladie auto-immune, comprenant l'administration à un besoin de celui-ci d'une quantité efficace d'un dérivé de benzo[c][2,7]naphtyridine, des procédés pour la modulation de l'activité de PDK-I, l'activité de PKA, l'activité de AKT, l'activité de S6K ou l'activité de PKC, comprenant l'administration à un sujet en besoin de celui-ci d'une quantité efficace d'un dérivé de benzo[c][2,7]naphtyridine. L'invention concerne également des procédés pour la préparation d'un dérivé de benzo[c][2,7]naphtyridine représentés par la formule (I).
• The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1)
  作者：Thomas Nittoli、Russell G. Dushin、Charles Ingalls、Katherine Cheung、M. Brawner Floyd、Heidi Fraser、Andrea Olland、Yongbo Hu、George Grosu、Xin Han

  DOI：10.1016/j.ejmech.2009.12.036

  日期：2010.4

  A series of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c] [2,7]naphthyridin-4-ylamine-based inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1) has been identified. Several examples appear to be potent and relatively selective inhibitors of PDK-1 over the related AGC kinases PKA, PKB/AKT, and p70S6K. The introduction of a stereochemical center beside the amino substituent on the aminoalkoxy-side chain had little effect upon the inhibitory activity against these enzymes, and X-ray crystallographic analyses of a representative pair of enantiomeric inhibitors bound to the active site of PDK-1 revealed comparable binding modes for each enantiomer. (C) 2009 Elsevier Masson SAS. All rights reserved.