tert-butyl (2S)-N-benzyloxycarbonyl-2,3-diaminopropionate hydrochloride

• 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: tert-butyl (2S)-N-benzyloxycarbonyl-2,3-diaminopropionate hydrochloride
• 英文别名: (S)-tert-butyl-3-amino-2-(((benzyloxy)carbonyl)amino)propanoate hydrochloride；2-(S)-Benzyloxycarbonyl-amino-2-tert-butoxycarbonyl-ethyl-ammonium chloride；tert-Butyl 2(S)-Benzyloxycarbonylamino-3-aminopropionate hydrochloride；[(2S)-3-[(2-methylpropan-2-yl)oxy]-3-oxo-2-(phenylmethoxycarbonylamino)propyl]azanium;chloride
• 化学式: C₁₅H₂₂N₂O₄*ClH
• 分子量: 330.812
• InChiKey: AKHQYGDAMJHTFV-YDALLXLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.0
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  90.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-N-benzyloxycarbonyl-2,3-diaminopropionate hydrochloride 在 palladium on activated charcoal 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 29.0h， 生成 tert-butyl 3-[3-fluoro-4-{(3S)-(pyrimidin-2-ylamino)piperidin-1-yl}benzoylamino]-(2S)-{(4-methoxybenzenesulfonyl)amino}propionate
  参考文献：
  名称：

  Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part III: Synthesis of potent antagonists with αvβ3/αIIbβ3 dual activity and improved water solubility

  摘要：

  In order to optimize our novel integrin alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonists, spatial screening at the N-terminus was performed. The alpha(v)beta(3) antagonistic activity varied depending on the space that was occupied by the N-terminus, but high potency against alpha(IIb)beta(3) was well maintained. The (3S)-aminopiperidine analogue had the strongest activity against alpha(v)beta(3), and the S isomer at piperidine was more potent than the R isomer. Compounds selected on the basis of SAR analysis of a novel lead compound showed acceptable early absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and sufficient water solubility for use as infusion drugs. Docking studies with the alpha(v)beta(3) receptor were performed to confirm the SAR findings. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.055

文献信息

• (<i>S</i>)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging
  作者：Xiaojiang Duan、Futao Liu、Hongmok Kwon、Youngjoo Byun、Il Minn、Xuekang Cai、Jingming Zhang、Martin G. Pomper、Zhi Yang、Zhen Xi、Xing Yang

  DOI：10.1021/acs.jmedchem.9b02031

  日期：2020.4.9

  prostate-specific membrane antigen (PSMA), 16 ligands (L1–L16) with structural modifications in S1′ binding pocket were synthesized and evaluated for PSMA inhibition. (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with Ki values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based

  为了寻求针对前列腺特异性膜抗原（PSMA）的新型药物，合成了16种在S1'结合口袋中具有结构修饰的配体（L1 - L16），并评估了其对PSMA的抑制作用。（S）-3-（羧甲酰胺基）-2-（3-（羧甲基）脲基）丙酸已被证明是有效的PSMA配体，其K i值在0.08 nM至8.98 nM范围内，或更高。与以前发布的基于尿素的配体相比，其效价更高。进行计算对接以研究发现的两个最有效配体的结合模式。FITC偶联的L14可以选择性地将PSMA + LNCaP细胞染色到PSMA之上–PC3细胞。IRDye800CW缀合的L16可以有效地在前列腺癌的小鼠异种移植模型中对肿瘤成像。
• Thiophene integrin inhibitors
  申请人：BioChem Pharma Inc.

  公开号：US06274620B1

  公开（公告）日：2001-08-14

  The present invention comprises compounds that are effective inhibitors of integrins, particularly &agr;v&bgr;3 and &agr;v&bgr;5 integrins. Particularly, the compounds are of formula I and pharmaceutically acceptable salts thereof wherein X,Y1 W, R1 to R5, A and B are defined according to the disclosure herein.

  本发明涉及有效抑制整合素的化合物，特别是αvβ3和αvβ5整合素。具体来说，所述化合物具有公式I和其药用盐，其中X、Y1、W、R1至R5、A和B根据本文所披露的定义。
• Pyridyl and naphthyridyl compounds for inhibiting osteoclast-mediated
  申请人：Merck & Co., Inc.

  公开号：US05741796A1

  公开（公告）日：1998-04-21

  Compounds of the following general structure X-Y-Z-Aryl-A-B, for example, ##STR1## which inhibit osteoclast mediated bone resorption. Specifically, the compounds are useful for treating mammals suffering from a bone condition caused or mediated by increased bone resorption, who are in need of such therapy. The compounds may be administered in oral dosage forms such as tablets, capsules, e.g. sustained release capsules, powders, granules, and suspensions.

  以下具有一般结构X-Y-Z-Aryl-A-B的化合物，例如##STR1##，可以抑制破骨细胞介导的骨吸收。具体而言，这些化合物可用于治疗因骨吸收增加引起或介导的骨病症状的哺乳动物，需要此类治疗。这些化合物可以以口服剂量形式给予，例如片剂、胶囊，例如持续释放胶囊，粉末，颗粒和悬浮液。
• Guainidino, formamidino, amino and related compounds for inhibiting
  申请人：Merck & Co., Inc.

  公开号：US05929120A1

  公开（公告）日：1999-07-27

  Compounds of the following general structure X--Y--Z-Aryl-A--B, ##STR1## which inhibit osteoclast mediated bone resorption.

  下列一般结构为X--Y--Z-Aryl-A--B的化合物，可以抑制破骨细胞介导的骨吸收。##STR1##
• THIOPHENE INTEGRIN INHIBITORS
  申请人：SHIRE BIOCHEM INC.

  公开号：EP1187825A1

  公开（公告）日：2002-03-20