3-benzamido-3-(4-nitrophenyl)propanoic acid

• 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: 3-benzamido-3-(4-nitrophenyl)propanoic acid
• 英文别名: 3-benzoylamino-3-(4-nitro-phenyl)-propionic acid；3-Benzoylamino-3-(4-nitro-phenyl)-propionsaeure；(R,S) 3-Benzoylamino-3-(4-nitrophenyl)-propionic acid；3-Benzoylamino-3-(4-nitrophenyl)-propionic acid
• 化学式: C₁₆H₁₄N₂O₅
• 分子量: 314.298
• InChiKey: AANAGSHHDRDBMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-benzamido-3-(4-nitrophenyl)propanoic acid 在 盐酸 、 异丁基硼酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 水 为溶剂， 生成 (R)-1-[3-benzamido-3-(4-nitrophenyl)propanamido]-3-methylbutylboronic acid
  参考文献：
  名称：

  Synthesis, in Vitro and in Vivo Biological Evaluation, and Comprehensive Understanding of Structure−Activity Relationships of Dipeptidyl Boronic Acid Proteasome Inhibitors Constructed from β-Amino Acids

  摘要：

  An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids is reported. SAR analysis revealed that bicyclic groups at the RI position, 3-F substituents at the R-2 position, and bulky aliphatic groups at the R-3 position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 mu M. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.

  DOI：

  10.1021/jm1009742
• 作为产物：
  描述：

  3-苯甲酰氨基-3-苯基丙酸 在 硝酸铵 、 硫酸 作用下， 生成 3-benzamido-3-(4-nitrophenyl)propanoic acid
  参考文献：
  名称：

  Rodionow et al., Zhurnal Obshchei Khimii, 1956, vol. 26, p. 520,524; engl. Ausg. S. 551, 554

  摘要：

  DOI：

文献信息

• Substituted bicyclic compounds
  申请人：——

  公开号：US20020156111A1

  公开（公告）日：2002-10-24

  The invention is directed to physiologically active compounds of general formula (I): 1 wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring system containing at least one heteroatom selected from O, S or N; R 1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; R 2 is hydrogen, halogen, lower alkyl or lower alkoxy; Z 1 is NR 5 ; L 1 is a —R 6 —R 7 — linkage (where R 6 is alkylene, alkenylene or alkynylene and R 7 is a direct bond, cycloalkylene, heterocycloalkylene, aryldiyl, heteroaryldiyl, —C(═Z 3 )—NR 5 —, —NR 5 —C(═Z 3 )—, —Z 3 —, —C(═O)—, —C(═NOR 5 )—, —NR 5 —, —NR 5 —C(═Z 3 )—NR 5 —, —SO 2 —NR 5 —, —NR 5 —SO 2 —, —O—C(═O)—, —C(═O)—O—, —NR 5 —C(═O)—O— or —O—C(═O)—NR 5 —); L 2 is an alkylene chain substituted by hydroxy, oxo, —OR 4 , —O—C(═O)—R 4 , —N(R 8 )—C(═O)—R 9 , —N(R 8 )—C(═O)—OR 9 , —N(R 8 )—SO 2 —R 9 , or —NY 3 Y 4 ; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (&agr;4&bgr;1).

  该发明涉及一般式(I)的生理活性化合物： 其中Het是一个可选择取代的、饱和的、部分饱和的或完全不饱和的含有至少一个来自O、S或N的杂原子的8到10成员的双环环系统；R 1 是可选择取代的芳基、杂环芳基、烷基、烯基、炔基、环烷基或杂环烷基；R 2 是氢、卤素、低烷基或低烷氧基；Z 1 是NR 5 ；L 1 是一个—R 6 —R 7 —连接（其中R 6 是烷基、烯基或炔基，R 7 是直接键、环烷基、杂环烷基、芳基二基、杂芳基二基、—C(═Z 3 )—NR 5 —、—NR 5 —C(═Z 3 )—、—Z 3 —、—C(═O)—、—C(═NOR 5 )—、—NR 5 —、—NR 5 —C(═Z 3 )—NR 5 —、—SO 2 —NR 5 —、—NR 5 —SO 2 —、—O—C(═O)—、—C(═O)—O—、—NR 5 —C(═O)—O—或—O—C(═O)—NR 5 —）；L 2 是被羟基、氧代、—OR 4 、—O—C(═O)—R 4 、—N(R 8 )—C(═O)—R 9 、—N(R 8 )—C(═O)—OR 9 、—N(R 8 )—SO 2 —R 9 或—NY 3 Y 4 取代的烷基链；Y是羧基或酸生物同位素；以及相应的N-氧化物，它们的前药；以及这些化合物及其N-氧化物和前药的药学上可接受的盐和溶剂。 这些化合物具有有价值的药理特性，特别是调节VCAM-1和纤维连接蛋白与整合素VLA-4（α4β1）相互作用的能力。
• SUBSTITUTED BICYCLIC COMPOUNDS
  申请人：Aventis Pharma Limited

  公开号：EP1177181A1

  公开（公告）日：2002-02-06
• [EN] SUBSTITUTED BICYCLIC COMPOUNDS<br/>[FR] COMPOSES BICYCLIQUES SUBSTITUES
  申请人：AVENTIS PHARMA LTD

  公开号：WO2000068213A1

  公开（公告）日：2000-11-16

  The invention is directed to physiologically active compounds of general formula (I): wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring system containing at least one heteroatom selected from O, S or N; R1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; R2 is hydrogen, halogen, lower alkyl or lower alkoxy; Z?1 is NR5; L1¿ is a -R6-R7- linkage (where R6 is alkylene, alkenylene or alkynylene and R7 is a direct bond, cycloalkylene, heterocycloalkylene, aryldiyl, heteroaryldiyl, -C(=Z?3)-NR5-, -NR5-C(=Z3)-, -Z3¿-, -C(=O)-, -C(=NOR?5)-, -NR5-, -NR5-C(=Z3)-NR5¿-, -SO¿2?-NR?5-, -NR5-SO¿2-, -O-C(=O)-, -C(=O)-O-, -NR5-C(=O)-O- or -O-C(=O)-NR5-); L2 is an alkylene chain substituted by hydroxy, oxo, -OR4, -O-C(=O)-R?4, -N(R8¿)-C(=O)-R?9, -N(R8¿)-C(=O)-OR?9, -N(R8)-SO¿2-R9, or -NY3 Y4; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1)
• Synthesis, in Vitro and in Vivo Biological Evaluation, and Comprehensive Understanding of Structure−Activity Relationships of Dipeptidyl Boronic Acid Proteasome Inhibitors Constructed from β-Amino Acids
  作者：Yongqiang Zhu、Gang Wu、Xinrong Zhu、Yuheng Ma、Xin Zhao、Yuejie Li、Yunxia Yuan、Jie Yang、Sen Yu、Feng Shao、Meng Lei

  DOI：10.1021/jm1009742

  日期：2010.12.23

  An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from beta-amino acids is reported. SAR analysis revealed that bicyclic groups at the RI position, 3-F substituents at the R-2 position, and bulky aliphatic groups at the R-3 position were favorable to the activities. Enzymatic screening results showed that compound 78, comprising all of these features, was the most active inhibitor against the 20S human proteasome at less than a 2 nM level, as active as the marketed drug bortezomib. Cellular assays confirmed that compound 78 was the most potent against two hematologic and some solid tumor cells with IC50 values less than 1 mu M. Pharmacokinetic profiles suggested that 78 showed higher plasma exposure and a longer half-life than bortezomib.
• Rodionow et al., Zhurnal Obshchei Khimii, 1956, vol. 26, p. 520,524; engl. Ausg. S. 551, 554
  作者：Rodionow et al.

  DOI：——

  日期：——