2-phenyl-2-[2-(1H-pyrrol-1-yl)phenoxy]acetic acid | 177578-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-phenyl-2-[2-(1H-pyrrol-1-yl)phenoxy]acetic acid
• 英文别名: 2-phenyl-2-(2-pyrrol-1-ylphenoxy)acetic acid
• CAS: 177578-77-7
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: GJFBVGMHULTJQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-phenyl-2-[2-(1H-pyrrol-1-yl)phenoxy]acetic acid 在 五氯化磷 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.0h， 以58%的产率得到5-phenyl-6-oxa-10b-aza-benzo[e]azulen-4-one
  参考文献：
  名称：

  Pyrrolobenzothiazepinones and Pyrrolobenzoxazepinones:  Novel and Specific Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors with Antiviral Activity

  摘要：

  Two novel classes of pyrrolobenzothiazepinones and pyrrolobenzoxazepinones were investigated as potential anti-AIDS drugs. These compounds were found to inhibit HIV-1 reverse transcriptase (RT) enzyme in vitro and to prevent HIV-1 cytopathogenicity in T4 lymphocytes, without appreciable activity on HIV-2 cytopathic effects, and against HBV as well as calf-thymus DNA alpha-polymerase. Their potency is influenced by substituents at position 6 and on the fused aromatic ring. Specifically, small lipophilic substituents at C-6 were preferred, whereas substitutions on the benzo-fused ring were found to be detrimental to activity, with respect to the unsubstituted compounds. Modification of the pi-system at C-6 is well tolerated, although the replacement of the benzo-fused with a [2,3]naphtho-fused ring leads to a less active compound. Maximum potency and specificity is achieved with a phenyl and an ethyl group at position 6 of the pyrrolobenzoxazepinone system. In the enzymatic assay the oxazepinone derivative (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5] 16e (IC50 = 0.25 mu M) was found to be more potent than nevirapine (IC50 = 0.5 mu M), tested in the same experimental conditions using rC . dG as a template-primer. In cell culture assay benzoxazepine 16e was active against HIV-1, both wild type and AZT-sensitive, and HIV-1 (IIIB) strains, but not against HIV-2. In enzyme assay although 16e inhibited HIV-1 RT, it was inactive against the nevirapine-resistant recombinant RT Y181C at 50 mu M. Molecular modeling studies suggest that these derivatives present a 3D pharmacophoric arrangement similar to that of other nonnucleoside inhibitors such as nevirapine.

  DOI：

  10.1021/jm950702c
• 作为产物：
  描述：

  2-(1H-吡咯-1-基)苯醇 在 sodium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 19.0h， 生成 2-phenyl-2-[2-(1H-pyrrol-1-yl)phenoxy]acetic acid
  参考文献：
  名称：

  Pyrrolobenzothiazepinones and Pyrrolobenzoxazepinones:  Novel and Specific Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors with Antiviral Activity

  摘要：

  Two novel classes of pyrrolobenzothiazepinones and pyrrolobenzoxazepinones were investigated as potential anti-AIDS drugs. These compounds were found to inhibit HIV-1 reverse transcriptase (RT) enzyme in vitro and to prevent HIV-1 cytopathogenicity in T4 lymphocytes, without appreciable activity on HIV-2 cytopathic effects, and against HBV as well as calf-thymus DNA alpha-polymerase. Their potency is influenced by substituents at position 6 and on the fused aromatic ring. Specifically, small lipophilic substituents at C-6 were preferred, whereas substitutions on the benzo-fused ring were found to be detrimental to activity, with respect to the unsubstituted compounds. Modification of the pi-system at C-6 is well tolerated, although the replacement of the benzo-fused with a [2,3]naphtho-fused ring leads to a less active compound. Maximum potency and specificity is achieved with a phenyl and an ethyl group at position 6 of the pyrrolobenzoxazepinone system. In the enzymatic assay the oxazepinone derivative (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5] 16e (IC50 = 0.25 mu M) was found to be more potent than nevirapine (IC50 = 0.5 mu M), tested in the same experimental conditions using rC . dG as a template-primer. In cell culture assay benzoxazepine 16e was active against HIV-1, both wild type and AZT-sensitive, and HIV-1 (IIIB) strains, but not against HIV-2. In enzyme assay although 16e inhibited HIV-1 RT, it was inactive against the nevirapine-resistant recombinant RT Y181C at 50 mu M. Molecular modeling studies suggest that these derivatives present a 3D pharmacophoric arrangement similar to that of other nonnucleoside inhibitors such as nevirapine.

  DOI：

  10.1021/jm950702c

文献信息

• TRICYCLIC OXAZEPINES AS IN VIVO IMAGING COMPOUNDS
  申请人：Hammersmith Imanet, Ltd

  公开号：EP2024373A1

  公开（公告）日：2009-02-18
• [EN] TRICYCLIC OXAZEPINES AS IN VIVO IMAGING COMPOUNDS<br/>[FR] OXAZÉPINES TRICYCLIQUES UTILISÉES EN TANT QUE COMPOSÉS D'IMAGERIE IN VIVO
  申请人：HAMMERSMITH IMANET LTD

  公开号：WO2007141491A1

  公开（公告）日：2007-12-13

  [EN] Novel compounds of formula (I): suitable for use as in vivo imaging agents are provided as well as precursors suitable for the preparation of said compounds.The present invention also provides pharmaceuticals comprising the compounds and kits for the preparation of the pharmaceuticals. Furthermore, use of the compounds for imaging peripheral benzodiazepine receptors in a subject is provided, in particular for imaging pathological conditions in which PBR are upregulated, e.g. Parkinson's disease, multiple sclerosis, Alzheimer's disease and Huntington's disease, neuropathic pain, arthritis, asthma, atherosclerosis and cancer.
  [FR] La présente invention concerne de nouveaux composés répondant à la formule (I), appropriés à une utilisation en tant qu'agents d'imagerie in vivo, ainsi que des précurseurs appropriés à la préparation desdits composés. La présente invention concerne également des produits pharmaceutiques contenant les composés et des trousses destinées à la préparation desdits produits pharmaceutiques. L'invention concerne en outre l'utilisation des composés pour l'imagerie des récepteurs périphériques de la benzodiazépine chez un sujet, en particulier, l'imagerie de pathologies caractérisées par une régulation à la hausse des récepteurs périphériques de la benzodiazépine, notamment la maladie de Parkinson, la sclérose en plaques, la maladie d'Alzheimer et la maladie de Huntington, la douleur névropathique, l'arthrite, l'asthme, l'athérosclérose et le cancer.
• Pyrrolobenzothiazepinones and Pyrrolobenzoxazepinones:  Novel and Specific Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors with Antiviral Activity
  作者：Giuseppe Campiani、Vito Nacci、Isabella Fiorini、Maria P. De Filippis、Antonio Garofalo、Giovanni Greco、Ettore Novellino、Sergio Altamura、Laura Di Renzo

  DOI：10.1021/jm950702c

  日期：1996.1.1

  Two novel classes of pyrrolobenzothiazepinones and pyrrolobenzoxazepinones were investigated as potential anti-AIDS drugs. These compounds were found to inhibit HIV-1 reverse transcriptase (RT) enzyme in vitro and to prevent HIV-1 cytopathogenicity in T4 lymphocytes, without appreciable activity on HIV-2 cytopathic effects, and against HBV as well as calf-thymus DNA alpha-polymerase. Their potency is influenced by substituents at position 6 and on the fused aromatic ring. Specifically, small lipophilic substituents at C-6 were preferred, whereas substitutions on the benzo-fused ring were found to be detrimental to activity, with respect to the unsubstituted compounds. Modification of the pi-system at C-6 is well tolerated, although the replacement of the benzo-fused with a [2,3]naphtho-fused ring leads to a less active compound. Maximum potency and specificity is achieved with a phenyl and an ethyl group at position 6 of the pyrrolobenzoxazepinone system. In the enzymatic assay the oxazepinone derivative (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5] 16e (IC50 = 0.25 mu M) was found to be more potent than nevirapine (IC50 = 0.5 mu M), tested in the same experimental conditions using rC . dG as a template-primer. In cell culture assay benzoxazepine 16e was active against HIV-1, both wild type and AZT-sensitive, and HIV-1 (IIIB) strains, but not against HIV-2. In enzyme assay although 16e inhibited HIV-1 RT, it was inactive against the nevirapine-resistant recombinant RT Y181C at 50 mu M. Molecular modeling studies suggest that these derivatives present a 3D pharmacophoric arrangement similar to that of other nonnucleoside inhibitors such as nevirapine.