(R)-2-((tert-butoxycarbonyl)amino)-3-(2-cyanophenyl)propanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-((tert-butoxycarbonyl)amino)-3-(2-cyanophenyl)propanoic acid
• 英文别名: Boc-D-o-cyanophenylalanine；Boc-2-cyano-D-phenylalanine；(2R)-3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: AJHPGXZOIAYYDW-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  99.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-((tert-butoxycarbonyl)amino)-3-(2-cyanophenyl)propanoic acid 在 palladium on activated charcoal 、 氢气 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 6.5h， 生成 [1-(4-hydroxy-2,6-dimethylbenzyl)-2(R)-(3-oxo-4(R)-phenylacetylamino-1,2,4,5-tetrahydrobenzo[c]azepin-2-yl)-ethyl]carbamic acid 9H-fluoren 9-ylmethyl ester
  参考文献：
  名称：

  A New Structural Motif for μ-Opioid Antagonists

  摘要：

  On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent mu-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the mu-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2',6'-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.

  DOI：

  10.1021/jm0491795

文献信息

• [EN] PYRIDAZINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE PYRIDAZINONE ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：GENENTECH INC

  公开号：WO2016112298A1

  公开（公告）日：2016-07-14

  The invention relates to compounds of formula (I) and salts thereof: wherein R1-R3 have any of the values defined in the specification. The compounds and salts are useful for treating PCAF mediated disorders and/or GCN5 mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as and methods of using said compounds, salts, or compositions in the treatment of various disorders.

  该发明涉及公式（I）的化合物及其盐：其中R1-R3具有规范中定义的任何值。这些化合物和盐对于治疗由PCAF介导的疾病和/或由GCN5介导的疾病是有用的。该发明还提供了包括公式（I）的化合物或其药学上可接受的盐的药物组合物，以及使用所述化合物、盐或组合物治疗各种疾病的方法。
• Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors
  作者：Jinyou Xu、Hyun O. Ok、Edward J. Gonzalez、Lawrence F. Colwell、Bahanu Habulihaz、Huaibing He、Barbara Leiting、Kathryn A. Lyons、Frank Marsilio、Reshma A. Patel、Joseph K. Wu、Nancy A. Thornberry、Ann E. Weber、Emma R. Parmee

  DOI：10.1016/j.bmcl.2004.06.099

  日期：2004.9

  equipotent thiazolidide 9. Extensive SAR studies on the phenyl ring of 9 led to the discovery of a novel series of potent and selective DP-IV inhibitors. Introduction of a fluorine at the 2-position proved to be crucial for the potency of this series. The 2,5-difluoro (22q) and 2,4,5-trifluoro (22t) analogues were potent inhibitors of DP-IV (IC(50)=270, 119nM, respectively).

  内部筛选铅β-氨基酰基脯氨酸8的修饰得到了等价的噻唑烷化物9。对9的苯环的广泛SAR研究导致发现了一系列新的有效的和选择性的DP-IV抑制剂。事实证明，在2位上引入氟对于该系列的效能至关重要。2,5-二氟（22q）和2,4,5-三氟（22t）类似物是DP-IV的有效抑制剂（分别为IC（50）= 270、119nM）。
• Therapeutic compounds and uses thereof
  申请人：GENENTECH, INC.

  公开号：US10239861B2

  公开（公告）日：2019-03-26

  The invention relates to compounds of formula (I) and salts thereof: wherein R1-R3 have any of the values defined in the specification. The compounds and salts are useful for treating PCAF mediated disorders and/or GCN5 mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as and methods of using said compounds, salts, or compositions in the treatment of various disorders.

  本发明涉及式（I）化合物及其盐类： 其中 R1-R3 具有说明书中定义的任何值。这些化合物和盐可用于治疗 PCAF 介导的疾病和/或 GCN5 介导的疾病。本发明还提供了包含式（I）化合物或其药学上可接受的盐的药物组合物，以及使用所述化合物、盐或组合物治疗各种疾病的方法。
• PYRIDAZINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER
  申请人：Genentech, Inc.

  公开号：EP3242874A1

  公开（公告）日：2017-11-15
• THERAPEUTIC COMPOUNDS AND USES THEREOF
  申请人：GENENTECH, INC.

  公开号：US20180037566A1

  公开（公告）日：2018-02-08

  The invention relates to compounds of formula (I) and salts thereof: wherein R 1 -R 3 have any of the values defined in the specification. The compounds and salts are useful for treating PCAF mediated disorders and/or GCN5 mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as and methods of using said compounds, salts, or compositions in the treatment of various disorders.