2-fluorobicyclo[4.2.0]octa-1(6),2,4-triene-7-carboxylic acid

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 2-fluorobicyclo[4.2.0]octa-1(6),2,4-triene-7-carboxylic acid
• 英文别名: 2-Fluorobicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic Acid
• 化学式: C₉H₇FO₂
• 分子量: 166.152
• InChiKey: SAAFUQNNJBPULR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,3-二氢-1,4-苯并二烷-5-基)哌嗪盐酸盐 、 2-fluorobicyclo[4.2.0]octa-1(6),2,4-triene-7-carboxylic acid 在 N,N'-羰基二咪唑 作用下， 生成 [4-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl]-(2-fluoro-bicyclo[4.2.0]octa-1(6),2,4-trien-7-yl)-methanone
  参考文献：
  名称：

  Characterization of Potent and Selective Antagonists at Postsynaptic 5-HT1A Receptors in a Series of N4-Substituted Arylpiperazines

  摘要：

  Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)pipe (3a) was chosen as a model of an arylpiperazine in view of its selectivity for 5-HT1A receptors versus alpha(1)-, alpha(2)-, and beta-adrenergic receptors, as well as dopamine D-1 and D-2 receptors. Two other closely-related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1-(benzofuran-7-yl)piperazine (3c), were also examined in this study. Al compounds showed high affinity at 5-HT1A sites (8.10 less than or equal to pK(i)s less than or equal to 9.35), and the majority behaved as antagonists in vivo in blocking the hypothermia induced by the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at equivalent doses. An in vivo evaluation of dopamine D-2 receptor antagonist properties revealed that the majority of compounds was devoid of activity at this site, in marked contrast to BMY 7378 which displayed virtually no selectivity for 5-HT1A versus dopamine D-2 receptors. Moreover, six compounds of the present series, 8, 10, 11, 14, 25, and, 37, showed > 10-fold selectivity in vitro for 5-HT1A versus alpha(1)-adrenergic receptors. Compound 14 displayed an optimal compromise between potency (pK(i) = 8.75), marked antagonist activity, and selectivity toward alpha(1)-adrenergic (81-fold) and dopamine D-2 (195-fold) receptors. These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The availability of 14 (S 15535) should facilitate the further elucidation of the functional role and potential therapeutic significance of 5-HT1A receptors.

  DOI：

  10.1021/jm00020a020
• 作为产物：
  描述：

  methyl 2-(2-bromo-5-fluorophenyl)acetate 在 palladium diacetate 、 sodium hydride 、 potassium carbonate 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 46.0h， 生成 2-fluorobicyclo[4.2.0]octa-1(6),2,4-triene-7-carboxylic acid
  参考文献：
  名称：

  [EN] NOVEL SUBSTITUTED N'-HYDROXYCARBAMIMIDOYL-1,2,5-OXADIAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS
  [FR] NOUVEAUX COMPOSÉS DE N'-HYDROXYCARBAMIMIDOYL -1,2,5-OXADIAZOLE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO)

  摘要：

  本文揭示了化合物的化学式(I)，或其药学上可接受的盐：化学式(I)。本文还揭示了所述化合物在潜在治疗或预防IDO相关疾病或紊乱中的用途。本文还揭示了包含所述化合物的组合物。本文还揭示了所述组合物在潜在治疗或预防IDO相关疾病或紊乱中的用途。

  公开号：

  WO2018044663A1

文献信息

• Substituted n′-hydroxycarbamimidoyl-1,2,5-oxadiazole compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10988487B2

  公开（公告）日：2021-04-27

  Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Formula (I). Also disclosed herein are uses of the compounds disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

  本文公开了一种式 (I) 的化合物或其药学上可接受的盐：式 (I)。本文还公开了本文公开的化合物在潜在治疗或预防 IDO 相关疾病或紊乱中的用途。本文还公开了包含本文公开的化合物的组合物。本文进一步公开了这些组合物在潜在治疗或预防 IDO 相关疾病或紊乱中的用途。
• NOVEL SUBSTITUTED N'-HYDROXYCARBAMIMIDOYL-1,2,5-OXADIAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3504185B1

  公开（公告）日：2021-11-24
• US5194437A
  申请人：——

  公开号：US5194437A

  公开（公告）日：1993-03-16
• Characterization of Potent and Selective Antagonists at Postsynaptic 5-HT1A Receptors in a Series of N4-Substituted Arylpiperazines
  作者：Jean-Louis Peglion、Herve Canton、Karin Bervoets、Valerie Audinot、Mauricette Brocco、Alain Gobert、Sylvie Le Marouille-Girardon、Mark J. Millan

  DOI：10.1021/jm00020a020

  日期：1995.9

  Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)pipe (3a) was chosen as a model of an arylpiperazine in view of its selectivity for 5-HT1A receptors versus alpha(1)-, alpha(2)-, and beta-adrenergic receptors, as well as dopamine D-1 and D-2 receptors. Two other closely-related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1-(benzofuran-7-yl)piperazine (3c), were also examined in this study. Al compounds showed high affinity at 5-HT1A sites (8.10 less than or equal to pK(i)s less than or equal to 9.35), and the majority behaved as antagonists in vivo in blocking the hypothermia induced by the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at equivalent doses. An in vivo evaluation of dopamine D-2 receptor antagonist properties revealed that the majority of compounds was devoid of activity at this site, in marked contrast to BMY 7378 which displayed virtually no selectivity for 5-HT1A versus dopamine D-2 receptors. Moreover, six compounds of the present series, 8, 10, 11, 14, 25, and, 37, showed > 10-fold selectivity in vitro for 5-HT1A versus alpha(1)-adrenergic receptors. Compound 14 displayed an optimal compromise between potency (pK(i) = 8.75), marked antagonist activity, and selectivity toward alpha(1)-adrenergic (81-fold) and dopamine D-2 (195-fold) receptors. These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The availability of 14 (S 15535) should facilitate the further elucidation of the functional role and potential therapeutic significance of 5-HT1A receptors.
• [EN] NOVEL SUBSTITUTED N'-HYDROXYCARBAMIMIDOYL-1,2,5-OXADIAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS DE N'-HYDROXYCARBAMIMIDOYL -1,2,5-OXADIAZOLE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO)
  申请人：MERCK SHARP & DOHME

  公开号：WO2018044663A1

  公开（公告）日：2018-03-08

  Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Formula (I). Also disclosed herein are uses of the compounds disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

  本文揭示了化合物的化学式(I)，或其药学上可接受的盐：化学式(I)。本文还揭示了所述化合物在潜在治疗或预防IDO相关疾病或紊乱中的用途。本文还揭示了包含所述化合物的组合物。本文还揭示了所述组合物在潜在治疗或预防IDO相关疾病或紊乱中的用途。