(RS)-3-amino-5-phenyl-3,4,6,7,-tetrahydropyrrolo<3,2,1-jk><1,4>benzodiazepin-4(3H)-one | 126149-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (RS)-3-amino-5-phenyl-3,4,6,7,-tetrahydropyrrolo<3,2,1-jk><1,4>benzodiazepin-4(3H)-one
• 英文别名: 3-amino-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one；(3RS)-3-amino-3,4,6,7-tetrahydro-4-oxo-1-phenylpyrrolo[3,2,1-jk][1,4]benzodiazepine；11-Amino-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one
• CAS: 126149-54-0
• 化学式: C₁₇H₁₅N₃O
• 分子量: 277.326
• InChiKey: MORIYLHQIVTWAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (RS)-3-amino-5-phenyl-3,4,6,7,-tetrahydropyrrolo<3,2,1-jk><1,4>benzodiazepin-4(3H)-one 在 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 硫酸 、 N-乙酰-L-苯丙氨酸 、 potassium nitrate 、 N,N-二异丙基乙胺 、 tin(ll) chloride 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.25h， 生成 (3R)-4-amino-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino [6,7,1-hi]indol-3-yl)-3,5-dichlorobenzamide
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Pharmacological Profile of 9-Amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6,7,1-hi]indoles:  Discovery of Potent, Selective Phosphodiesterase Type 4 Inhibitors

  摘要：

  The synthesis, structure-activity relationships, and biological properties of a novel series of; potent and selective phosphodiesterase type 4 (PDE4) inhibitors are described. These new aminodiazepinoindoles displayed in vitro PDE4 activity with submicromolar IC50 values and PDE4 selectivity vs PDE1, -3, and -5. Specifically, one compound (CI-1044, 10e) provided efficient in vitro inhibition of TNF alpha release from hPBMC and; hWB with IC50:values of 0.34 and 0.84 muM, respectively. This compound was found to exhibit potent in vivo activity in antigen-induced eosinophil recruitment in Brown-Norway rats (ED50 = 3.2 mg/kg po) and in production of TNF alpha in Wistar fats (ED50 = 2.8; mg/kg po). No emetic side effects at therapeutic doses were observed in ferrets.

  DOI：

  10.1021/jm000315p
• 作为产物：
  描述：

  2,3-二氢-1H-吲哚-7-基(苯基)甲酮 在 吡啶 、 sodium hydroxide 、 盐酸羟胺 、 氨 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 (RS)-3-amino-5-phenyl-3,4,6,7,-tetrahydropyrrolo<3,2,1-jk><1,4>benzodiazepin-4(3H)-one
  参考文献：
  名称：

  Studies on a Novel, Potent and Orally Effective Cholecystokinin A Antagonist, FK-480. Synthesis and Structure-Activity Relationships of FK-480 and Related Compounds.

  摘要：

  我们制备了多种新型三环1,4-苯并二氮杂䓬衍生物作为胆囊收缩素（CCK）A受体拮抗剂，并初步评估了它们对<125>I-CCK-8与大鼠胰腺膜体外结合的抑制作用以及对CCK-8诱导的小鼠活性炭餐胃排空的抑制作用。基于构效关系（SAR）研究以及这些化合物的起始原料的稳定性和可获得性，我们选择了(S)-N-[1-(2-氟苯基)-3,4,6,7-四氢-4-氧代-吡咯并[3,2,1-jk][1,4]苯并二氮杂䓬-3-基]-1H-吲哚-2-甲酰胺（9f, FK-480）作为候选化合物进行进一步评估。通过与(S)-α-甲基苄基异氰酸酯的脲基衍生物的X射线晶体学研究，确定了FK-480前体(3S)-氨基-1,4-苯并二氮杂䓬衍生物（(S)-8a, R1=F）的绝对构型。FK-480目前正在进行治疗慢性胰腺炎的临床研究。

  DOI：

  10.1248/cpb.42.2071

文献信息

• [EN] MALONAMIDE DERIVATIVES AS GAMMA-SECRETASE INHIBITORS<br/>[FR] DERIVES DE MALONAMIDE UTILISES COMME INHIBITEURS DE LA GAMMA-SECRETASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004069826A1

  公开（公告）日：2004-08-19

  The invention relates to malonamide derivatives of formula (IA) or (IB) and to pharmaceutically suitable acid addition salts thereof. The compounds are Ϝ-secretase inhibitors and the related compounds may be useful in the treatment of Alzheimer's disease.

  这项发明涉及公式（IA）或（IB）的马隆酰胺衍生物及其药用适宜的酸盐。这些化合物是Ϝ-分泌酶抑制剂，相关化合物可能在治疗阿尔茨海默病方面有用。
• Tricyclic compounds
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04981847A1

  公开（公告）日：1991-01-01

  Tricyclo benzodiazepines are cholecystokinin antagonists.

  三环苯二氮卓类药物是胆囊收缩素拮抗剂。
• Malonamide derivatives
  申请人：——

  公开号：US20040220222A1

  公开（公告）日：2004-11-04

  The invention relates to malonamide derivatives of formula 1 wherein 2 is a cyclic ring, selected from the group consisting of phenyl, pyridinyl, furanyl, benzo[b]thiophenyl, tetrahydronaphthyl, indanyl, 2,2-dimethyl-[1,3]dioxolanyl and tetrahydrofuranyl; 3 is selected from the group consisting of 4 and R 1 , R 1′ , R 2 , R 3 , R 11 , R 12 , R 13 , R 14 , n and X are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof The compounds are &ggr;-secretase inhibitors. Thus, the invention also relates to pharmaceutical compositions containing these compounds and to a method of treating Alzheimer's disease by administering the compounds of the invention.

  本发明涉及公式1的马隆酰胺衍生物，其中2是选自苯基、吡啶基、呋喃基、苯[b]噻吩基、四氢萘基、茚基、2,2-二甲基-[1,3]二氧杂环己基和四氢呋喃基的环状环，3选自4和R1、R1′、R2、R3、R11、R12、R13、R14、n和X，如规范中所定义，并且其药学上可接受的酸盐。这些化合物是&ggr;-分泌酶抑制剂。因此，本发明还涉及含有这些化合物的制药组合物，并通过给予本发明的化合物治疗阿尔茨海默病的方法。
• Tricyclic compounds, processes for their preparation and pharmaceutical compositions comprising them
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0360079A1

  公开（公告）日：1990-03-28

  A compound of the formula : wherein R1 is aryl which may have suitable substituent(s), X is -O- or (in which R3 is hydrogen or lower alkyl), A is a bond or lower alkylene which may have lower alkyl group(s), and R2 is hydrogen or an acyl group, and a pharmaceutically acceptable salt thereof, processes for their preparation and pharmaceutical compositions comprising them as an active ingredient in admixture with pharmaceutically acceptable carriers.

  式中的化合物 式中 R1 是芳基，可具有合适的取代基、 X 是 -O- 或 (其中 R3 为氢或低级烷基）、 A 是键或低级亚烷基，可带有低级烷基，以及 R2 是氢或酰基、 及其药学上可接受的盐、 它们的制备工艺以及由它们作为活性成分与药学上可接受的载体混合而成的药物组合物。
• J. Med. Chem. 2000, 43, 4850-4867
  作者：

  DOI：——

  日期：——