tert-butyl 8-fluoro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate | 1174568-46-7

• 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: tert-butyl 8-fluoro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate
• 英文别名: 8-Fluoro-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepine-4-carboxylic acid tert-butyl ester；tert-butyl 8-fluoro-2-oxo-3,5-dihydro-1H-1,4-benzodiazepine-4-carboxylate
• CAS: 1174568-46-7
• 化学式: C₁₄H₁₇FN₂O₃
• 分子量: 280.299
• InChiKey: UZHQFJLFXGSCIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 8-fluoro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate 在 三乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.03h， 生成 4-((S)-3-amino-3-((S)-5,6-difluoro-2,3-dihydro-1H-inden-1-yl)propanoyl)-8-fluoro-4,5-dihydro-1H-benzo[e][1,4]diazepin-2(3H)-one
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Fused β-Homophenylalanine Derivatives as Potent DPP-4 Inhibitors

  摘要：

  Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused beta-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.

  DOI：

  10.1021/acsmedchemlett.5b00074
• 作为产物：
  描述：

  4-氟-2-硝基甲苯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 铁粉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.08h， 生成 tert-butyl 8-fluoro-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepine-4(5H)-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Fused β-Homophenylalanine Derivatives as Potent DPP-4 Inhibitors

  摘要：

  Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused beta-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.

  DOI：

  10.1021/acsmedchemlett.5b00074

文献信息

• Heterocyclic compounds
  申请人：Jain Rajesh

  公开号：US08455479B2

  公开（公告）日：2013-06-04

  The present invention relates to novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers including R and S isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising compounds of Formula I and methods of treating or preventing one or more conditions that may be regulated or normalized via inhibition of dipeptidyl peptidase IV (DPP-IV).

  本发明涉及一种新的I式化合物，其药学上可接受的衍生物，互变异构体，包括R和S异构体，多晶形，前药，代谢物，盐或其溶剂。本发明还涉及合成新的I式化合物，其药学上可接受的衍生物，互变异构体，立体异构体，多晶形，前药，代谢物，盐或其溶剂的过程。本发明还提供了包含I式化合物的制药组合物，以及通过抑制二肽基肽酶IV（DPP-IV）来治疗或预防可以通过调节或规范的一种或多种情况的方法。
• NOVEL HETEROCYCLIC COMPOUNDS
  申请人：Jain Rajesh

  公开号：US20100311732A1

  公开（公告）日：2010-12-09

  The present invention relates to novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers including R and S isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising compounds of Formula I and methods of treating or preventing one or more conditions that may be regulated or normalized via inhibition of dipeptidyl peptidase IV (DPP-IV).

  本发明涉及一种新型I式化合物，其药学上可接受的衍生物、互变异构体、立体异构体（包括R和S异构体）、多晶形、前药、代谢物、盐或溶剂化物。本发明还涉及制备新型I式化合物、其药学上可接受的衍生物、互变异构体、立体异构体、多晶形、前药、代谢物、盐或溶剂化物的方法。本发明还提供了包含I式化合物的制药组合物和通过抑制二肽基肽酶IV（DPP-IV）来治疗或预防可能通过调节或规范的一种或多种情况的方法。
• [EN] PYRIDINE DERIVATIVE RELATED TO KMD5 PATHWAY<br/>[FR] DÉRIVÉ DE PYRIDINE LIÉ À LA VOIE KMD5<br/>[ZH] 与KMD5通路相关的吡啶衍生物
  申请人：MEDSHINE DISCOVERY INC

  公开号：WO2019154261A1

  公开（公告）日：2019-08-15

  本发明公开了一类吡啶衍生物，具体公开了式(Ⅲ)所示化合物及其药学上可接受的盐。
• [EN] NOVEL HETEROCYCLIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES
  申请人：PANACEA BIOTEC LTD

  公开号：WO2009093269A9

  公开（公告）日：2009-10-15
• US8455479B2
  申请人：——

  公开号：US8455479B2

  公开（公告）日：2013-06-04