(S)-tert-butyl 1-(2-chlorophenyl)-3-hydroxypropan-2-ylcarbamate | 944470-58-0

• 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: (S)-tert-butyl 1-(2-chlorophenyl)-3-hydroxypropan-2-ylcarbamate
• 英文别名: tert-butyl [(1S)-1-(2-chlorobenzyl)-2-hydroxyethyl]carbamate；tert-butyl N-[(2S)-1-(2-chlorophenyl)-3-hydroxypropan-2-yl]carbamate
• CAS: 944470-58-0
• 化学式: C₁₄H₂₀ClNO₃
• 分子量: 285.771
• InChiKey: ZXBMTCISXZJBSZ-NSHDSACASA-N

物化性质

• 沸点：
  437.4±40.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 1-(2-chlorophenyl)-3-hydroxypropan-2-ylcarbamate 在 ammonium acetate 、 三苯基膦 、 lithium hexamethyldisilazane 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 6.25h， 生成 tert-butyl (S)-(1-((5-(4-amino-8,9-dimethoxybenzo[c][2,7]naphthyridin-2-yl)pyridin-3-yl)oxy)-3-(2-chlorophenyl)propan-2-yl)carbamate
  参考文献：
  名称：

  WO2008/109613

  摘要：

  公开号：
• 作为产物：
  描述：

  L-2-氯苯丙氨酸 在 锂硼氢 、 三甲基氯硅烷 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 生成 (S)-tert-butyl 1-(2-chlorophenyl)-3-hydroxypropan-2-ylcarbamate
  参考文献：
  名称：

  New thiazole carboxamides as potent inhibitors of Akt kinases

  摘要：

  A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)-2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3 beta proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.080

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] BICYCLIC HETEROAROMATIC AMIDE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS AMIDES HÉTÉROAROMATIQUES BICYCLIQUES ET LEURS UTILISATIONS
  申请人：KINETA INC

  公开号：WO2023107597A2

  公开（公告）日：2023-06-15

  The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

  本发明的特点是化合物可用于治疗神经系统疾病。本发明的化合物可单独使用，也可与其他药物活性剂结合使用，用于治疗或预防神经系统疾病。
• Syntheses of Potent, Selective, and Orally Bioavailable Indazole-Pyridine Series of Protein Kinase B/Akt Inhibitors with Reduced Hypotension
  作者：Gui-Dong Zhu、Viraj B. Gandhi、Jianchun Gong、Sheela Thomas、Keith W. Woods、Xiaohong Song、Tongmei Li、R. Bruce Diebold、Yan Luo、Xuesong Liu、Ran Guan、Vered Klinghofer、Eric F. Johnson、Jennifer Bouska、Amanda Olson、Kennan C. Marsh、Vincent S. Stoll、Mulugeta Mamo、James Polakowski、Thomas J. Campbell、Ruth L. Martin、Gary A. Gintant、Thomas D. Penning、Qun Li、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1021/jm0701019

  日期：2007.6.1

  Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.
• 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.
• New thiazole carboxamides as potent inhibitors of Akt kinases
  作者：Shaohua Chang、Zhang Zhang、Xiaoxi Zhuang、Jinfeng Luo、Xianwen Cao、Honglin Li、Zhengchao Tu、Xiaoyun Lu、Xiaomei Ren、Ke Ding

  DOI：10.1016/j.bmcl.2011.11.080

  日期：2012.1

  A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)-2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3 beta proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents. (C) 2011 Elsevier Ltd. All rights reserved.