(+)-1,1-dimethylethyl<<<4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11(R)-yl)-1-piperidinyl>-carbonyl>-methyl>-1-piperidinecarboxylate | 193276-76-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: (+)-1,1-dimethylethyl<<<4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11(R)-yl)-1-piperidinyl>-carbonyl>-methyl>-1-piperidinecarboxylate
• 英文别名: (R)-tert-Butyl 4-(2-(4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl)-2-oxoethyl)piperidine-1-carboxylate；tert-butyl 4-[2-[4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl]-2-oxoethyl]piperidine-1-carboxylate
• CAS: 193276-76-5
• 化学式: C₃₁H₃₈Br₂ClN₃O₃
• 分子量: 695.922
• InChiKey: RMGMZHYJLCICSR-MUUNZHRXSA-N

物化性质

• 沸点：
  707.5±60.0 °C(Predicted)
• 密度：
  1.436±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-1,1-dimethylethyl<<<4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11(R)-yl)-1-piperidinyl>-carbonyl>-methyl>-1-piperidinecarboxylate 在 盐酸 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 16.0h， 生成 洛那法尼
  参考文献：
  名称：

  一种新的对映选择性烷基化及其在抗癌剂合成中的应用。

  摘要：

  报道了具有仲亲电试剂的双苄基底物的新型对映选择性烷基化。合成了一种简单的基于去氧麻黄碱的手性配体，该烷基化产物的收率为95％，ee为95％。揭示了对对映选择性的独特水效应。使用许多双苄基底物和第二亲电试剂可获得良好至优异的ee值。该新反应已被应用于有希望的抗癌剂的合成。

  DOI：

  10.1021/jo034380t
• 作为产物：
  描述：

  4-<3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11-ylidene>-1-piperidinecarboxylic acid ethyl ester 在 盐酸 、 乙胺嗪 、 二异丁基氢化铝 、 1-羟基苯并三唑 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 40.67h， 生成 (+)-1,1-dimethylethyl<<<4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11(R)-yl)-1-piperidinyl>-carbonyl>-methyl>-1-piperidinecarboxylate
  参考文献：
  名称：

  (+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide (SCH-66336):  A Very Potent Farnesyl Protein Transferase Inhibitor as a Novel Antitumor Agent

  摘要：

  We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.

  DOI：

  10.1021/jm980462b

文献信息

• Novel N-substituted urea inhibitors of farnesyl-protein transferase
  申请人：——

  公开号：US20020119981A1

  公开（公告）日：2002-08-29

  Novel halo-N-substituted urea compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel halo-N-substituted urea compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.

  本发明涉及一种新型的卤代-N-取代脲类化合物和制药组合物，它们是韦尼酰基蛋白转移酶的抑制剂。同时，本发明还公开了一种抑制Ras功能，从而抑制细胞异常生长的方法。该方法包括将新型的卤代-N-取代脲类化合物用于生物系统。特别地，该方法可抑制哺乳动物，如人类中细胞的异常生长。
• NOVEL N-SUBSTITUTED UREA INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0989979A1

  公开（公告）日：2000-04-05
• US6358968B1
  申请人：——

  公开号：US6358968B1

  公开（公告）日：2002-03-19
• US6699872B2
  申请人：——

  公开号：US6699872B2

  公开（公告）日：2004-03-02
• [EN] NOVEL N-SUBSTITUTED UREA INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE<br/>[FR] NOUVEAUX COMPOSES D'UREE N-SUBSTITUES INHIBITEURS DE LA FARNESYL TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：WO1998057948A1

  公开（公告）日：1998-12-23

  (EN) Novel halo-N-substituted urea compounds and pharmaceutical compositions of formula (1.0) or a pharmaceutically acceptable salt or solvate theroef, are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel halo-N-substituted urea compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.(FR) La présente invention concerne de nouveaux composés d'urée halogéno N-substitués et des compositions pharmaceutiquement acceptables de formules (1.0) ainsi que leurs sels ou solvates pharmaceutiquement acceptables, qui sont des inhibiteurs de l'enzyme farnésyl transférase. La présente invention concerne également une méthode d'inhibition de la fonction Ras et donc de la croissance anormale des cellules. Cete méthode, qui consiste à administrer le nouveau composé d'urée halogéno N-substitué à un système biologique permet notamment d'inhiber la croissance anormale des cellules chez des mammifères tel que l'homme.