3-amino-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione | 170856-32-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-amino-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione
• 英文别名: 3-amino-1H-1,5-benzodiazepine-2,4(3H,5H)-dione；3-amino-1,5-dihydro-1,5-benzodiazepine-2,4-dione
• CAS: 170856-32-3
• 化学式: C₉H₉N₃O₂
• 分子量: 191.189
• InChiKey: BZZQVDQDOOUGRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  504.1±50.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione 在 盐酸 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 1,5-bis-(cyclopropylcarbonylmethyl)-3-amino-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione
  参考文献：
  名称：

  有力和亚型选择性CCK-B /胃泌素受体拮抗剂：具有对称平面的2,4-二氧-1,5-苯并二氮杂pine。

  摘要：

  设计，合成了一系列具有对称平面的CCK-B /胃泌素受体拮抗剂，2,4-二氧代-1,5-苯并二氮杂卓衍生物，并评估了其拮抗活性。构效关系研究表明，在N-1和N-5位置上的羰基甲基和亲水基团（例如在C-3位置与脲基相连的苯环上的羧基）带来了强大的亲和力和亚型对CCK-B /胃泌素受体的选择性。在麻醉的大鼠中，几种化合物对五肽胃泌素诱导的胃酸分泌具有出色的体内抑制作用。

  DOI：

  10.1016/s0968-0896(97)00083-7
• 作为产物：
  描述：

  1,5-dihydrobenzo[b][1,4]diazepine-2,3,4-trione 3-(O-methyloxime) 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以62%的产率得到3-amino-1H-1,5-benzodiazepine-2,4-(3H,5H)-dione
  参考文献：
  名称：

  有力和亚型选择性CCK-B /胃泌素受体拮抗剂：具有对称平面的2,4-二氧-1,5-苯并二氮杂pine。

  摘要：

  设计，合成了一系列具有对称平面的CCK-B /胃泌素受体拮抗剂，2,4-二氧代-1,5-苯并二氮杂卓衍生物，并评估了其拮抗活性。构效关系研究表明，在N-1和N-5位置上的羰基甲基和亲水基团（例如在C-3位置与脲基相连的苯环上的羧基）带来了强大的亲和力和亚型对CCK-B /胃泌素受体的选择性。在麻醉的大鼠中，几种化合物对五肽胃泌素诱导的胃酸分泌具有出色的体内抑制作用。

  DOI：

  10.1016/s0968-0896(97)00083-7

文献信息

• Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds
  申请人：——

  公开号：US20020045747A1

  公开（公告）日：2002-04-18

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

  公开了抑制β-淀粉样肽释放和/或其合成的化合物，因此可用于治疗阿尔茨海默病。还公开了包含抑制β-淀粉样肽释放和/或其合成的化合物的药物组合物，以及使用这些药物组合物预防性和治疗性治疗阿尔茨海默病的方法。
• [EN] PIPERAZINE SUBSTITUTED ARYL BENZODIAZEPINES<br/>[FR] ARYL BENZODIAZEPINES SUBSTITUEES PAR DE LA PIPERAZINE
  申请人：LILLY CO ELI

  公开号：WO2004014895A1

  公开（公告）日：2004-02-19

  Described herein are compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, S, and O; Alk is (C1-4) alkylene or hydroxy substituted (C1-4) alkylene; X is oxygen or sulfur; R1 is hydrogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, or -CN; R2 is H, halogen, (C1-6) fluoroalkyl, (C1-6) cycloalkyl, OR4, SR4, N02, CN, COR4, C(O)OR4, CONR5R6 , NR5R6, S02NR5R6, NR5COR4, NR5SO2R4, optionally substituted aromatic, or (C1-6) alkyl, wherein (C1-6) alkyl is unsubstituted or substituted with a hydroxy group; R3 is hydrogen, (C1-6) fluoroalkyl, (C2-6) alkenyl, Ar, (C1-4)alkyl-Ar, or (C1-4) alkyl wherein (C1-4) alkyl is unsubsituted or substituted with a phenyl; R4 is hydrogen, (C1-6 alkyl, (C1-6) fluoroalkyl, or optionally substituted aromatic; R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted aromatic, R7 is hydrogen, (C1-6) alkyl, (C1-6) fluoroalkyl, or optionally substituted aromatic; R8 and R9 are independently hydrogen, (C1-6) alkyl, or optionally substituted aromatic; Ar is optionally substituted phenyl, napthyl, monocyclic heteroaromatic or bicyclic heteroaromatic; Z1 and Z2 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, NR8R9, and optionally substituted aromatic; and all salts, solvates, optical and geometric isomers, and crystalline forms thereof. Also, described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treament of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了以下式(I)的化合物：其中：是一个可选的苯并嵌合的五元或六元芳香环，其中含有从N、S和O中独立选择的零至三个杂原子；Alk是(C1-4)烷基或羟基取代的(C1-4)烷基；X是氧或硫；R1是氢、(C1-6)氟烷基、(C3-6)环烷基或(C1-4)烷基，其中(C1-4)烷基未取代或取代为羟基、甲氧基、乙氧基、OCH2CH2OH或-CN；R2是H、卤素、(C1-6)氟烷基、(C1-6)环烷基、OR4、SR4、N02、CN、COR4、C(O)OR4、CONR5R6、NR5R6、S02NR5R6、NR5COR4、NR5SO2R4、可选取代的芳香基或(C1-6)烷基，其中(C1-6)烷基未取代或取代为羟基；R3是氢、(C1-6)氟烷基、(C2-6)烯基、Ar、(C1-4)烷基-Ar或(C1-4)烷基，其中(C1-4)烷基未取代或取代为苯基；R4是氢、(C1-6)烷基、(C1-6)氟烷基或可选取代的芳香基；R5和R6独立地是氢、(C1-6)烷基或可选取代的芳香基，R7是氢、(C1-6)烷基、(C1-6)氟烷基或可选取代的芳香基；R8和R9独立地是氢、(C1-6)烷基或可选取代的芳香基；Ar是可选取代的苯基、萘基、单环杂芳基或双环杂芳基；Z1和Z2独立地选自氢、卤素、(C1-6)烷基、(C1-6)氟烷基、OR7、SR7、NO2、CN、COR7、CONR8R9、NR8R9和可选取代的芳香基；以及其所有盐、溶剂化合物、光学和几何异构体以及结晶形式。此外，还描述了将上述式(I)的化合物用作多巴胺D2受体拮抗剂以及用于治疗精神病和双相情感障碍的药剂，以及上述式(I)的药物配方。
• [EN] PIPERAZINE SUBSTITUTED ARYL BENZODIAZEPINES AND THEIR USE AS DOPAMINE RECEPTOR ANTAGONISTS FOR THE TREATMENT OF PSYCHOTIC DISORDERS<br/>[FR] ARYLES BENZODIAZEPINES A SUBSTITUTION DE PIPERAZINE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DE RECEPTEUR DE DOPAMINE DANS LE TRAITEMENT DE TROUBLES PSYCHOTIQUES
  申请人：LILLY CO ELI

  公开号：WO2003082877A1

  公开（公告）日：2003-10-09

  Described herein are antipyschotic compounds of formula (I) wherein, A is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; Alk is (C1-4) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R1 is hydrogen or (C1-4) alkyl optionally substituted with OH, OR3, or OCH2CH2OH, wherein R3 is (C1-2) alkyl; R2 is H, (C1-6) alkyl, halogen, fluorinated (C1-6) alkyl, OR4, SR4, NO2, CN, COR4, CONR5R6, SO2NR5R6, NR5R6, NR5COR4, NR5SO2R4, or optionally substituted phenyl,wherein R4 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, benzyl, or optionally substituted phenyl, R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, SO2NR8R9, NR8SO2R7, NR8R9, or optionally substituted phenyl, wherein R7 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, benzyl, or optionally substituted phenyl, R8 and R9 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I). Also described are compounds useful as intermediates for the synthesis of the compounds of formula (I).

  本文描述了公式（I）的抗精神药物化合物，其中，A是一个可选的苯并嵌有零至三个异原子（N、O和S）的五元或六元芳香环；Alk是（C1-4）烷基烯，可选地取代为OH、甲氧基、乙氧基或F；Ar是可选取代的苯基、萘基、单环杂芳基或双环杂芳基；R1是氢或（C1-4）烷基，可选地取代为OH、OR3或OCH2CH2OH，其中R3是（C1-2）烷基；R2是H、（C1-6）烷基、卤素、氟代（C1-6）烷基、OR4、SR4、NO2、CN、COR4、CONR5R6、SO2NR5R6、NR5R6、NR5COR4、NR5SO2R4或可选取代的苯基，其中R4是氢、（C1-6）烷基、氟代（C1-6）烷基、苄基或可选取代的苯基，R5和R6独立地是氢、（C1-6）烷基或可选取代的苯基；Z是一个或两个取代基，独立地选自氢、卤素、（C1-6）烷基、氟代（C1-6）烷基、OR7、SR7、NO2、CN、COR7、CONR8R9、SO2NR8R9、NR8SO2R7、NR8R9或可选取代的苯基，其中R7是氢、（C1-6）烷基、氟代（C1-6）烷基、苄基或可选取代的苯基，R8和R9独立地是氢、（C1-6）烷基或可选取代的苯基；以及其盐、溶剂合物和晶型。还描述了将公式（I）的化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相障碍的药物，以及公式（I）的化合物的制剂。还描述了作为公式（I）化合物合成的中间体有用的化合物。
• Benzodiazepine derivatives as app modulators
  申请人：——

  公开号：US20040082572A1

  公开（公告）日：2004-04-29

  A novel class of 1,4- and 1,5-benzodiazepines of formula (I) is disclosed. The compounds modulate the processing of amyloid precursor protein by &ggr;-secretase, and hence find use in the treatment or prevention of conditions associated with the deposition of &bgr;-amyloid, such as Alzheimer's disease. 1

  公开了一种式(I)的新型1,4-和1,5-苯二氮平类化合物。这些化合物调节&ggr;-分泌酶对淀粉样前体蛋白的加工作用，因此可用于治疗或预防与&bgr;-淀粉样蛋白沉积相关的疾病，如阿尔茨海默病。
• [EN] BENZODIAZEPINE DERIVATIVES AS APP MODULATORS<br/>[FR] DERIVES DE BENZODIAZEPINE UTILISES COMME MODULATEURS DE LA PROTEINE PRECURSEUR AMYLOIDE (APP)
  申请人：MERCK SHARP & DOHME

  公开号：WO2001090084A1

  公开（公告）日：2001-11-29

  A novel class of 1,4- and 1,5-benzodiazepines of formula (I) is disclosed. The compounds modulate the processing of amyloid precursor protein by η-secretase, and hence find use in the treatment or prevention of conditions associated with the deposition of β-amyloid, such as Alzheimer's disease.

  一种新型的1,4-和1,5-苯二氮平类化合物的式(I)被揭示。这些化合物通过调节η-分泌酶对淀粉样前体蛋白的加工，因此可用于治疗或预防与β-淀粉样蛋白沉积有关的疾病，如阿尔茨海默病。