1,3-di-(4-fluorophenyl)-4,7-dihydro-4,7-methano-2H-isoindole | 316124-14-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 1,3-di-(4-fluorophenyl)-4,7-dihydro-4,7-methano-2H-isoindole
• 英文别名: 3,5-Bis(4-fluorophenyl)-4-azatricyclo[5.2.1.02,6]deca-2,5,8-triene
• CAS: 316124-14-8
• 化学式: C₂₁H₁₅F₂N
• 分子量: 319.354
• InChiKey: IMVOJEMXLCTUSD-UHFFFAOYSA-N

物化性质

• 熔点：
  189 °C
• 沸点：
  453.2±45.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  15.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,3-di-(4-fluorophenyl)-4,7-dihydro-4,7-methano-2H-isoindole 在 10percent Pd/C 环己烯 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 1,3-di-(4-fluorophenyl)-4,7-methano-4,5,6,7-tetrahydro-2H-isoindole
  参考文献：
  名称：

  1,3-Diaryl-4,5,6,7-tetrahydro-2H-isoindole Derivatives:  A New Series of Potent and Selective COX-2 Inhibitors in Which a Sulfonyl Group Is Not a Structural Requisite

  摘要：

  Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,S-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC50 = 0.6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED50 for inhibition of exudate PGE2 of 3 mg/kg and gastric PGEB of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED50 values for edema inhibition in the noninjected paw of 0.35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.

  DOI：

  10.1021/jm990965x
• 作为产物：
  描述：

  氟苯 在 二硫化碳 、 三氯化铝 、 ammonium acetate 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 24.0h， 生成 1,3-di-(4-fluorophenyl)-4,7-dihydro-4,7-methano-2H-isoindole
  参考文献：
  名称：

  1,3-Diaryl-4,5,6,7-tetrahydro-2H-isoindole Derivatives:  A New Series of Potent and Selective COX-2 Inhibitors in Which a Sulfonyl Group Is Not a Structural Requisite

  摘要：

  Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,S-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC50 = 0.6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED50 for inhibition of exudate PGE2 of 3 mg/kg and gastric PGEB of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED50 values for edema inhibition in the noninjected paw of 0.35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.

  DOI：

  10.1021/jm990965x

文献信息

• Nouveaux derives de pyrrole leur procédé de preparation et les compositions pharmaceutiques qui les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0921119A1

  公开（公告）日：1999-06-09

  Composés de formule (I) : dans laquelle : Rreprésente un atome d'hydrogène, un groupement alkyle, un groupement amino éventuellement substitué ou un groupement acyle (C1-C6) linéaire ou ramifié, R1, R2,identiques ou différents, représentent chacun indépendamment l'un de l'autre un groupement aryle, hétéroaryle ou cycloalkyle (C5-C7), chacun de ces groupements pouvant être éventuellement substitué, A,avec les atomes communs du pyrrole, représente un cycloalkyle (C3-C12), monocyclique ou bicyclique, saturé ou insaturé, un hétérocycle saturé de 5 à 7 chaînons contenant un ou deux atomes d'azote ou un oxa-7 bicyclo[2.2.1]heptane, chacun de ces cycles pouvant être éventuellement substitué, leurs isomères ainsi que leurs sels d'addition à un acide ou à une base pharmaceutiquement acceptable. Medicaments.

  式(I)化合物 其中： R 代表氢原子、烷基、任选取代的氨基或直链或支链（C1-C6）酰基、 R1 和 R2（可以相同或不同）各自独立地代表芳基、杂芳基或（C5-C7）环烷基，其中每个基团都有可能被任选取代、 A，连同吡咯的公共原子，代表饱和或不饱和、单环或双环（C3-C12）环烷基、含有一个或两个氮原子的饱和 5 至 7 元杂环或 7-氧杂双环[2.2.1]庚烷，其中每个环都可能被任选取代、 它们的异构体及其与药学上可接受的酸或碱的加成盐。 药物。
• 高純度β−ヒドロキシエチルジメチルヒドラジニウムヒドロキシドの製造方法
  申请人：日本ヒドラジン工業株式会社

  公开号：JP2000007636A

  公开（公告）日：2000-01-11

  (57)【要約】 （修正有）\n【課題】 高純度β−ヒドロキシエチルジメチルヒドラジニウムヒドロキシドの製造方法を提供する。\n【解決手段】 エチレンオキシド付加副生成物を含むβ−ヒドロキシエチルジメチルヒドラジニウム化合物と１，１’−ビス−β−ナフトールなどを反応させて副生成物を含まないβ−ヒドロキシエチルジメチルヒドラジニウム包接錯体を分離し、これを炭酸ガスと反応分解させ、高純度β−ヒドロキシエチルジメチルヒドラジニウム−カーボネイト及び／又は−ビカーボネイトを取得する。この水溶液を陽イオン交換膜隔膜で電気分解してβ−ヒドロキシエチルジメチルヒドラジニウムヒドロキシドを副生成物や他のアニオンの挟雑なしに水溶液の形で得る。この水溶液に目的物の分解生成物であるアンモニアやＮ，Ｎ−ジメチルエタノールアミンが混在する場合には水溶液を減圧濃縮して留去する。

  (57）[摘要]（有修改）．n[问题]提供一种生产高纯度β-羟乙基二甲基肼氢氧化物的方法。\将含有环氧乙烷加成副产物的 β-羟乙基二甲基肼化合物与 1,1'-双-β-萘酚等反应。通过与 1,1'-双-β-萘酚等反应，分离出不含副产物的 β-羟乙基二甲基肼包合物，然后通过与二氧化碳气体反应进行分解，得到高纯度的 β-羟乙基二甲基肼-碳酸盐和/或-碳酸氢盐。该溶液在阳离子交换膜隔膜上进行电解，以获得不含副产物或其他阴离子的水溶液形式的 β-羟乙基二甲基肼氢氧化物。如果水溶液中含有目标产物的分解产物氨或 N,N-二甲基乙醇胺，则通过减压浓缩溶液将其去除。
• US6063804A
  申请人：——

  公开号：US6063804A

  公开（公告）日：2000-05-16
• US6114360A
  申请人：——

  公开号：US6114360A

  公开（公告）日：2000-09-05
• 1,3-Diaryl-4,5,6,7-tetrahydro-2<i>H</i>-isoindole Derivatives:  A New Series of Potent and Selective COX-2 Inhibitors in Which a Sulfonyl Group Is Not a Structural Requisite
  作者：Bernard Portevin、Charles Tordjman、Philippe Pastoureau、Jacqueline Bonnet、Guillaume De Nanteuil

  DOI：10.1021/jm990965x

  日期：2000.11.1

  Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,S-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC50 = 0.6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED50 for inhibition of exudate PGE2 of 3 mg/kg and gastric PGEB of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED50 values for edema inhibition in the noninjected paw of 0.35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.