2-hydroxy-3-(3-phenylpropyl)benzoic acid | 93434-76-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2-hydroxy-3-(3-phenylpropyl)benzoic acid
• CAS: 93434-76-5
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: VPTXPMBNBZLRET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-溴水杨酸 在 aluminum (III) chloride 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 20.0~160.0 ℃ 、101.33 kPa 条件下， 反应 13.33h， 生成 2-hydroxy-3-(3-phenylpropyl)benzoic acid
  参考文献：
  名称：

  Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors

  摘要：

  HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl] benzoic acid (25) was selectively active against integrase strand transfer, with an IC50 of 3.7 mu M. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3'-processing and strand transfer with IC50 values of 11 +/- 4 and 5 +/- 2 mu M, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl) acryloyl] benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl) acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 mu M, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r(2) of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q(2) and r(2) values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC(50) values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.047

文献信息

• Pharmaceutical preparations containing a mollusc extract
  申请人：Mc Farlane, Stuart John

  公开号：EP0010061B1

  公开（公告）日：1983-07-13
• US4455298A
  申请人：——

  公开号：US4455298A

  公开（公告）日：1984-06-19
• [EN] PHARMACEUTICAL PREPARATIONS
  申请人：——

  公开号：WO1980000661A1

  公开（公告）日：1980-04-17

  (EN) Novel pharmaceutical preparations containing A) an extract of the mollusc Perna canaliculus, a mussel which is found on the shores of New Zealand, and B) a pharmaceutically active substance, especially medicaments having anti-phlogistic, anti-pyretic and/or analgetic action, which, when taken per se, may cause as a side effect imitation of the gastro-intestinal mucosae and possibly the formation of ulcers. The addition of a mollusc extract according to A) to the said medicaments has a gastro-protective action, in that the occurrence of the said side effects is prevented or diminished. The component A) is preferably used as a dry powder of the whole of the flesh of the mollusc or a dry powder obtained from the gonads thereof. In a typical preparation according to the invention an extract of the gonads is e.g. combined with acetyl-salicylic acid. The preparations may contain the 2 components in one and the same dosage unit form, e.g. a capsule or in 2 different ones, e.g. a capsule and a tablet. The invention also includes a method for preventing, alleviating or treating gastro-intestinal imitation or ulcer formation by administering an effective amount of the mollusc extract as defined under A. (FR) Nouvelles preparations pharmaceutiques contenant A) un extrait du mollusque Perna canaliculus, une moule que l"on trouve sur les cotes de Nouvelle-Zelande, et B) une substance pharmaceutique active, specialement des medicaments ayant une activite antiphlogistique, antipyretique e/ou analgesique, qui, lorsqu"ils sont pris per se, peuvent entrainer un effet secondaire d"irritation de la muqueuse gastro-intestinale et eventuellement former des ulceres, L"addition d"un extrait de mollusques selon A) auxdits medicaments presente une action gastro-protectrice, dans le sens que lesdits effets secondaires sont elimines ou diminues. Le composant A) est utilise de preference sous forme d"une poudre seche de la totalite de la chair du mollusque ou sous forme d"une poudre seche obtenue a partir de ces gonades. Dans une preparation caracteristique selon l"invention, un extrait des gonades est par exemple combine avec de l"acide acetylsalicylique. Les preparations peuvent contenir les deux composants dans une meme et unique forme d"unite de dosage, p. ex. une capsule ou en deux formes differentes, p.ex. une capsule et un comprime. Methodes preventives, calmantes ou de traitement des irritations gastro-intestinales ou de formation d"ulceres en administrant une quantite effective de l"extrait de mollusques tel qu"il est defini sous A.
• Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors
  作者：Horrick Sharma、Shivaputra Patil、Tino W. Sanchez、Nouri Neamati、Raymond F. Schinazi、John K. Buolamwini

  DOI：10.1016/j.bmc.2011.01.047

  日期：2011.3

  HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl] benzoic acid (25) was selectively active against integrase strand transfer, with an IC50 of 3.7 mu M. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3'-processing and strand transfer with IC50 values of 11 +/- 4 and 5 +/- 2 mu M, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl) acryloyl] benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl) acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 mu M, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r(2) of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q(2) and r(2) values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC(50) values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors (C) 2011 Elsevier Ltd. All rights reserved.