(S)-tert-butyl 3-(3,4-dichlorophenyl)-1-hydroxypropan-2-ylcarbamate | 944470-64-8

• 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 3-(3,4-dichlorophenyl)-1-hydroxypropan-2-ylcarbamate
• 英文别名: tert-butyl [(1S)-1-(3,4-dichlorobenzyl)-2-hydroxyethyl]carbamate；N-(t-butyloxycarbonyl)-(D)-(m,p-dichloro)phenylalaninol；tert-butyl N-[(2S)-1-(3,4-dichlorophenyl)-3-hydroxypropan-2-yl]carbamate
• CAS: 944470-64-8
• 化学式: C₁₄H₁₉Cl₂NO₃
• 分子量: 320.216
• InChiKey: IJGQDOXDMWLOHD-JTQLQIEISA-N

物化性质

• 沸点：
  463.2±45.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 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 3-(3,4-dichlorophenyl)-1-hydroxypropan-2-ylcarbamate 在 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (1S)-1-(3,4-dichlorobenzyl)-2-[5-(3-methyl-1H-indazol-5-yl)pyridin-3-yloxy]-ethylamine tristrifluoroacetate
  参考文献：
  名称：

  Syntheses of Potent, Selective, and Orally Bioavailable Indazole-Pyridine Series of Protein Kinase B/Akt Inhibitors with Reduced Hypotension

  摘要：

  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.

  DOI：

  10.1021/jm0701019
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (S)-2-aMino-3-(3,4-dichlorophenyl)propan-1-ol 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 (S)-tert-butyl 3-(3,4-dichlorophenyl)-1-hydroxypropan-2-ylcarbamate
  参考文献：
  名称：

  [EN] FLUOROISOQUINOLINE SUBSTITUTED THIAZOLE COMPOUNDS AND METHODS OF USE
  [FR] THIAZOLES SUBSTITUÉS PAR FLUOROISOQUINOLÉINE ET LEURS MÉTHODES D'APPLICATION

  摘要：

  该发明涉及式(I)的噻唑化合物及其组合物，用于治疗由蛋白激酶B（PKB）介导的疾病，其中变量具有此处提供的定义。该发明还涉及在治疗与异常细胞生长、癌症、炎症和代谢紊乱相关的疾病状态中使用这种噻唑化合物和其组合物的治疗用途。

  公开号：

  WO2010083246A1

文献信息

• O-thiocarbamoyl-aminoalkanol compounds, their pharmaceutically useful
  申请人：Yukong Limited

  公开号：US05935997A1

  公开（公告）日：1999-08-10

  The present invention relates to O-thiocarbamoyl-aminoalkanol compound represented by the following structural formula (VI), (VIII) and (IX) which are a racemic or enantiomerically enriched and pharmaceulically acceptable salts thereof to treat diseases of the central nervous system: ##STR1## wherein Ar is a phenyl group as described as follows: ##STR2## wherein R is a member selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, halogen selected from F, Cl, Br, and I, alkoxy containing 1 to 3 carbon atoms, thioalkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, or taifluorocarbon, and x is an integer from 1 to 3, with the proviso that R is the same or different when x is 2 or 3. R.sub.1 and R.sub.2 may be the same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, aryl, 3 to 7-membered aliphatic cyclic compounds and R.sub.1 and R.sub.2, together with the adjoining N-atom, form a 5 to 7-membered cyclic compound which optionally comprises zero to one additional nitrogen atoms substituted with a member selected from the group consisting of hydrogen, alkyl and aryl groups, or zero to one oxygen atoms directly unconnected, R.sub.3 and R.sub.4 may be same or different from each other and are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, aryl, 3 to 7-membercd aliphatic cyclic compounds and R.sub.3 and R.sub.4, together with the adjoining N-atom, form a 5 to 7-membered cyclic compound which optidonally comprises zero to one additional nitrogen atoms substituted with a member selected from the group consisting of hydrogen, alkyl and aryl groups, or zero to one oxygen atoms directly unconnected, each of l, m and n is zero or 1, and the pharmaceutically acceptable salts thereof.

  本发明涉及以下结构式（VI）、（VIII）和（IX）所代表的O-硫代氨基醇化合物，其为一个外消旋或旋光异构体富集的药用盐，用于治疗中枢神经系统疾病：其中Ar是如下所述的苯基：其中R是从氢、1至8个碳原子的低碳烷基、从F、Cl、Br和I中选择的卤素、含有1至3个碳原子的烷氧基、含有1至3个碳原子的硫代烷氧基、硝基、羟基或氟氯烷基中选择的一种成员，x是1至3的整数，但R在x为2或3时相同时或不同。R.sub.1和R.sub.2可以相同也可以不同，独立地选择自氢、1至8个碳原子的低碳烷基、芳基、3至7个成员的脂肪环化合物和R.sub.1和R.sub.2，连同相邻的N原子，形成一个含有0至1个额外氮原子的5至7个成员的环化合物，该氮原子被从氢、烷基和芳基中选择的成员取代，或0至1个直接不连接的氧原子，R.sub.3和R.sub.4可以相同也可以不同，独立地选择自氢、1至8个碳原子的低碳烷基、芳基、3至7个成员的脂肪环化合物和R.sub.3和R.sub.4，连同相邻的N原子，形成一个含有0至1个额外氮原子的5至7个成员的环化合物，该氮原子被从氢、烷基和芳基中选择的成员取代，或0至1个直接不连接的氧原子，l、m和n中的每一个为零或1，以及其药用盐。
• FLUOROISOQUINOLINE SUBSTITUTED THIAZOLE COMPOUNDS AND METHODS OF USE
  申请人：Zeng Qingping

  公开号：US20110263647A1

  公开（公告）日：2011-10-27

  The invention relates to thiazole compounds of Formula I and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such thiazole compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  本发明涉及一种式I的噻唑化合物及其组合物，其在治疗由蛋白激酶B（PKB）介导的疾病方面具有用途，其中变量具有本文所提供的定义。本发明还涉及在治疗与异常细胞生长、癌症、炎症和代谢紊乱有关的疾病状态中使用此类噻唑化合物和其组合物的治疗用途。
• 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.
• O-THIOCARBAMOYL-AMINOALKANOL COMPOUNDS, THEIR PHARMACEUTICALLY ACCEPTABLE SALTS AND PROCESS FOR PREPARING THE SAME
  申请人：SK Corporation

  公开号：EP1149076B1

  公开（公告）日：2003-10-22
• US5935997A
  申请人：——

  公开号：US5935997A

  公开（公告）日：1999-08-10