3-(9H-fluoren-ylmethoxycarbonylamino)-5-(4-hydroxybenzyl)benzoic acid | 869096-90-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 3-(9H-fluoren-ylmethoxycarbonylamino)-5-(4-hydroxybenzyl)benzoic acid
• 英文别名: 3-(9H-fluoren-9-ylmethoxycarbonylamino)-5-(4-hydroxybenzyl)benzoic acid；3-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[(4-hydroxyphenyl)methyl]benzoic acid
• CAS: 869096-90-2
• 化学式: C₂₉H₂₃NO₅
• 分子量: 465.505
• InChiKey: UKGYKWBFNMFHSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(9H-fluoren-ylmethoxycarbonylamino)-5-(4-hydroxybenzyl)benzoic acid 、 [2-(叠氮基甲基)苯基]乙酸 以9.4 mg的产率得到2-(2-((3-(4-Hydroxybenzyl)-5-aminobenzamido)methyl)phenyl)acetic acid
  参考文献：
  名称：

  Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2

  摘要：

  Analogues of the hexapeptide angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr(2) and a phenylacetic or benzoic acid moiety replacing His4-Pro5-Phe6 have been synthesized and evaluated in biological assays. The analogues inhibited the proteolytic activity of cystinyl aminopeptidase ( CAP), frequently referred to as the insulin-regulated aminopeptidase ( IRAP), and were found less efficient as inhibitors of aminopeptidase N (AP-N). The best Ang IV mimetics in the series were approximately 20 times less potent than Ang IV as IRAP inhibitors. Furthermore, it was found that the ligands at best exhibited a 140 times lower binding affinity to the membrane-bound IRAP/AT4 receptor than Ang IV. Although the best compounds still exert lower activities than Ang IV, it is notable that these compounds comprise only two amino acid residues and are considerably less peptidic in character than the majority of the Ang IV analogues previously reported as IRAP inhibitors in the literature. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.046
• 作为产物：
  描述：

  3-(9H-fluoren-9-ylmethoxycarbonyl)amino-5-(4-methoxybenzyl)benzoic acid 在 boron trifluoride-dimethyl sulfide complex 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 以93%的产率得到3-(9H-fluoren-ylmethoxycarbonylamino)-5-(4-hydroxybenzyl)benzoic acid
  参考文献：
  名称：

  Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2

  摘要：

  Analogues of the hexapeptide angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr(2) and a phenylacetic or benzoic acid moiety replacing His4-Pro5-Phe6 have been synthesized and evaluated in biological assays. The analogues inhibited the proteolytic activity of cystinyl aminopeptidase ( CAP), frequently referred to as the insulin-regulated aminopeptidase ( IRAP), and were found less efficient as inhibitors of aminopeptidase N (AP-N). The best Ang IV mimetics in the series were approximately 20 times less potent than Ang IV as IRAP inhibitors. Furthermore, it was found that the ligands at best exhibited a 140 times lower binding affinity to the membrane-bound IRAP/AT4 receptor than Ang IV. Although the best compounds still exert lower activities than Ang IV, it is notable that these compounds comprise only two amino acid residues and are considerably less peptidic in character than the majority of the Ang IV analogues previously reported as IRAP inhibitors in the literature. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.046

文献信息

• Angiotensin II Pseudopeptides Containing 1,3,5-Trisubstituted Benzene Scaffolds with High AT₂ Receptor Affinity
  作者：Jennie Georgsson、Christian Sköld、Bianca Plouffe、Gunnar Lindeberg、Milad Botros、Mats Larhed、Fred Nyberg、Nicole Gallo-Payet、Adolf Gogoll、Anders Karlén、Anders Hallberg

  DOI：10.1021/jm050280z

  日期：2005.10.1

  Two 1,3,5-trisubstituted aromatic scaffolds intended to serve as gamma-turn mimetics have been synthesized and incorporated in five pseudopeptide analogues of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), replacing Val-Tyr-Ile, Val-Tyr, or Tyr-Ile. All the tested compounds exhibited nanomolar affinity for the AT(2) receptor with the best compound (3) having a K-i of 1.85 nM. Four pseudopeptides were AT(2) selective, while one (5) also exhibited good affinity for the AT(1) receptor (K-i = 30.3 nM). This pseudopeptide exerted full agonistic activity in an AT(2) receptor induced neurite outgrowth assay but displayed no agonistic effect in an AT(2) receptor functional assay. Molecular modeling, using the program DISCOtech, showed that the high-affinity ligands could interact similarly with the AT(2) receptor as other ligands with high affinity for this receptor. A tentative agonist model is proposed for AT(2) receptor activation by angiotensin 11 analogues. We conclude that the 1,3,5-trisubstituted benzene rings can be conveniently prepared and are suitable as gamma-turn mimics.
• Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2
  作者：Hanna Andersson、Heidi Demaegdt、Georges Vauquelin、Gunnar Lindeberg、Anders Karlén、Mathias Hallberg

  DOI：10.1016/j.bmc.2008.05.046

  日期：2008.7

  Analogues of the hexapeptide angiotensin IV (Ang IV, Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr(2) and a phenylacetic or benzoic acid moiety replacing His4-Pro5-Phe6 have been synthesized and evaluated in biological assays. The analogues inhibited the proteolytic activity of cystinyl aminopeptidase ( CAP), frequently referred to as the insulin-regulated aminopeptidase ( IRAP), and were found less efficient as inhibitors of aminopeptidase N (AP-N). The best Ang IV mimetics in the series were approximately 20 times less potent than Ang IV as IRAP inhibitors. Furthermore, it was found that the ligands at best exhibited a 140 times lower binding affinity to the membrane-bound IRAP/AT4 receptor than Ang IV. Although the best compounds still exert lower activities than Ang IV, it is notable that these compounds comprise only two amino acid residues and are considerably less peptidic in character than the majority of the Ang IV analogues previously reported as IRAP inhibitors in the literature. (c) 2008 Elsevier Ltd. All rights reserved.