2-benzyloxycarbonylamino-1,3-diphenyl-4,7-dihydro-2H-isoindole | 229153-49-5

• 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-benzyloxycarbonylamino-1,3-diphenyl-4,7-dihydro-2H-isoindole
• 英文别名: 1,3-diphenyl-2-benzyloxycarbonylamino-4,7-dihydro-2H-isoindole；benzyl N-(1,3-diphenyl-4,7-dihydroisoindol-2-yl)carbamate
• CAS: 229153-49-5
• 化学式: C₂₈H₂₄N₂O₂
• 分子量: 420.511
• InChiKey: DLECTQZPAHUNBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  43.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-benzyloxycarbonylamino-1,3-diphenyl-4,7-dihydro-2H-isoindole 在 10percent Pd/C 吡啶 、 ammonium formate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 1,3-diphenyl-2-methanesulphonylamino-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：

  肼基甲酸苄酯 、 (6-benzoylcyclohex-3-enyl)(phenyl)methanone 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 2-benzyloxycarbonylamino-1,3-diphenyl-4,7-dihydro-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

• Pyrrole compounds
  申请人：Adir et Compagnie

  公开号：US06063804A1

  公开（公告）日：2000-05-16

  Compounds of formula (I): ##STR1## wherein: R represents hydrogen, alkyl, optionally-substituted amino, or linear or branched (C.sub.1 -C.sub.6)-acyl, R.sub.1 and R.sub.2, which may be identical or different, each represents independently of the other aryl, heteroaryl, or (C.sub.5 -C.sub.7)-cycloalkyl, or one of those groups optionally substituted, A, together with the atoms in common with the pyrrole, represents saturated or unsaturated, monocyclic or bicyclic (C.sub.3 -C.sub.12)-cycloalkyl, or a saturated heterocycle having 5 to 7 ring members and containing one or two nitrogen, or 7-oxabicyclo[2.2.1]heptane, or one of those groups optionally substituted, their isomers, and also addition salts thereof with a pharmaceutically-acceptable acid or base, pharmaceutical compositions thereof, and use thereof as medicaments.

  式(I)的化合物：##STR1## 其中：R代表氢、烷基、可选取代的氨基或线性或支链(C.sub.1-C.sub.6)-酰基，R.sub.1和R.sub.2，它们可以相同或不同，每个独立地代表芳基、杂芳基或(C.sub.5-C.sub.7)-环烷基，或这些基团中的一个可选取代的基团，A与吡咯共有的原子一起代表饱和或不饱和、单环或双环(C.sub.3-C.sub.12)-环烷基，或含有5至7个环成员并含有一或两个氮的饱和杂环，或7-氧代双环[2.2.1]庚烷，或这些基团中的一个可选取代的基团，它们的异构体，以及与药学上可接受的酸或碱的加合物，其制备的制药组合物，以及其作为药物的用途。
• Olefin polymerization catalyst component, olefin polymerization catalyst and process for producing olefin polymer
  申请人：SUMITOMO CHEMICAL COMPANY, LIMITED

  公开号：EP0761694A1

  公开（公告）日：1997-03-12

  An olefin polymerization catalyst component represented by the general formula (1); (wherein M is the transition-metai element of the 4th Group or the Lanthanide Series in the Periodic Table and 0 is an oxygen atom. Each of A and A' is a hydrocarbon or halogenated hydrocarbon having 1 to 50 carbon atoms, or a hydrocarbon or halogenated hydrocarbon group having 1 to 50 carbon atoms and a substituent containing an oxygen atom, and A and A' may be the same or different. B is a residual group of an element of the 13th to 15th Groups capable of forming bonds at three positions. Each of X and X' is a halogen atom or a hydrocarbon group having 1 to 20 carbon atoms and X and X' may be the same or different. Y represents a hydrocarbon or halogenated hydrocarbon group containing at least one hetero atom and having 1 to 20 carbon atoms.), an olefin polymerization catalyst containing the said catalyst component, and a process for producing an olefin polymer with the said catalyst.

  由通式(1)表示的烯烃聚合催化剂组分； (其中 M 为元素周期表中第 4 族或镧系的过渡金属元素，0 为氧原子。A 和 A'中的每一个都是具有 1 至 50 个碳原子的烃或卤代烃，或具有 1 至 50 个碳原子的烃或卤代烃基团和含有氧原子的取代基，A 和 A'可以相同或不同。B 是第 13 至第 15 组元素的残基，能在三个位置形成键。X 和 X'中的每一个都是卤素原子或具有 1 至 20 个碳原子的烃基，X 和 X'可以相同或不同。Y 代表含有至少一个杂原子并具有 1 至 20 个碳原子的烃基或卤代烃基）、含有上述催化剂组分的烯烃聚合催化剂，以及用上述催化剂生产烯烃聚合物的工艺。
• 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。
• US5840646A
  申请人：——

  公开号：US5840646A

  公开（公告）日：1998-11-24
• US6034190A
  申请人：——

  公开号：US6034190A

  公开（公告）日：2000-03-07