2-(3-Allyl-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide | 174180-47-3

• 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: 2-(3-Allyl-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide
• 英文别名: 2-(3-methyl-2,4-dioxo-5-phenyl-3-prop-2-enyl-1,5-benzodiazepin-1-yl)-N-phenyl-N-propan-2-ylacetamide
• CAS: 174180-47-3
• 化学式: C₃₀H₃₁N₃O₃
• 分子量: 481.594
• InChiKey: DLUWAFIPZDNQJK-UHFFFAOYSA-N

物化性质

• 沸点：
  713.9±60.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  60.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-Allyl-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide 在 ruthenium trichloride 、 sodium periodate 、 水 作用下， 以 四氯化碳 为溶剂， 反应 24.0h， 以92%的产率得到2-[3-methyl-2,4-dioxo-1-[2-oxo-2-(N-propan-2-ylanilino)ethyl]-5-phenyl-1,5-benzodiazepin-3-yl]acetic acid
  参考文献：
  名称：

  3-[2-(N-Phenylacetamide)]-1,5-benzodiazepines:  Orally Active, Binding Selective CCK-A Agonists

  摘要：

  A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in. vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.

  DOI：

  10.1021/jm960205b
• 作为产物：
  描述：

  2-bromo-N-isopropyl-N-phenyl-acetamide 在 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 生成 2-(3-Allyl-3-methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide
  参考文献：
  名称：

  3-[2-(N-Phenylacetamide)]-1,5-benzodiazepines:  Orally Active, Binding Selective CCK-A Agonists

  摘要：

  A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in. vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.

  DOI：

  10.1021/jm960205b

文献信息

• CCK or gastrin modulating benzo \x9bb!\x9b1,4! diazepines derivatives
  申请人：Glaxo Wellcome Inc.

  公开号：US05859007A1

  公开（公告）日：1999-01-12

  Benzo\x9bb!\x9b1,4!diazepine compounds of formula (I), where R.sup.1 is selected from C.sub.1 C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl, or substituted phenyl; R.sup.2 is selected from C.sub.3 -C.sub.6 alkyl, C.sub.3 C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 alkenyl, benzyl, phenylC.sub.1 -C.sub.3 alkyl of substituted phenyl; or NR.sup.1 R.sup.2 together form 1,2,3,4-tetrahydroquinoline or benzazepine, mono-, di-, or trisubstituted independently with C.sub.1-6 alkyl C.sub.1-6 alkoxy or halogen substituents; p is an integer 0 or 1; q is an integer 0 or 1; r is an integer 0 or 1; t is an integer 0 or 1, provided that when r is 0 then t is 0; R.sup.3, R.sup.5, and R.sup.6 are independently hydrogen or C.sub.1-6 alkyl; R.sup.4 is C.sub.1-6 alkyl or C.sub.1-6 alkenyl; R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 cycloalkyl, C.sub.1-6 alkenyl, phenyl, substituted phenyl, napthyl, heteroaryl, substituted heteroaryl, bicycloheteroaryl or substituted bicycloheteroaryl; or NR.sup.6 R.sup.7 together form a saturated 5,6, or 7 membered ring optionally interrupted by 1,2,3 or 4 N, S or O heteroatoms, with the proviso that any two O or S atoms are not bonded to each other, m is an integer selected from the group of 0, 1, 2, 3 or 4; R.sup.8 and R.sup.9 are selected from a variety of substituents; Z is hydrogen or halogen; novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).

  以下是您提供的化学公式和描述的中文翻译： 本专利涉及1,4-苯并二氮杂卓化合物，其分子式为(I)，其中R1选自C1-C6烷基、C3-C6环烷基、苯基或取代苯基；R2选自C3-C6烷基、C3-C6环烷基、C3-C6烯基、苄基、苯基C1-C3烷基或取代苯基；或NR1R2共同形成1,2,3,4-四氢喹啉或苯并氮卓环，且单独或同时以C1-6烷基、C1-6烷氧基或卤素取代基进行单、双或三取代；p为0或1的整数；q为0或1的整数；r为0或1的整数；t为0或1的整数，条件是当r为0时，t也为0；R3、R5和R6独立地为氢或C1-6烷基；R4为C1-6烷基或C1-6烯基；R7选自氢、C1-6烷基、C1-6环烷基、C1-6烯基、苯基、取代苯基、萘基、杂芳基、取代杂芳基、双环杂芳基或取代双环杂芳基；或NR6R7共同形成一个由1,2,3或4个N、S或O杂原子隔断的饱和的5,6或7元环，条件是任意两个O或S原子不得相互连接；m为0、1、2、3或4的整数；R8和R9选自多种取代基；Z为氢或卤素；本专利还包括新颖的中间体、用于治疗肥胖、胆囊淤滞、胰腺分泌障碍的药物组合物，以及用于治疗这些疾病的方法和制备公式(I)化合物的方法。
• [EN] CCK OR GASTRIN MODULATING 1,5 BENZODIAZEPINES DERIVATIVES<br/>[FR] DERIVES DES 1,5-BENZODIAZEPINES PRESENTANT UNE ACTIVITE MODULATRICE DE LA COLECYSTOKININE (CCK) OU DE LA GASTRINE
  申请人：GLAXO WELLCOME INC.

  公开号：WO1995028391A1

  公开（公告）日：1995-10-26

  (EN) 1,5 Benzodiazepine compounds of formula (I), where R1 is selected from C1-C6alkyl, C3-C6cycloalkyl, phenyl, or substituted phenyl; R2 is selected from C3-C6alkyl, C3-C6cycloalkyl, C3-C6alkenyl, benzyl, phenylC1-C3alkyl or substituted phenyl; or NR1R2 together form 1,2,3,4-tetrahydroquinoline or benzazepine, mono-, di-, or trisubstituted independently with C1-6alkyl, C1-6alkoxy or halogen substituents; p is an integer 0 or 1; q is an integer 0 or 1; r is an integer 0 or 1; t is an integer 0 or 1, provided that when r is 0 then t is 0; R3, R5 and R6 are independently hydrogen or C1-6alkyl; R4 is C1-6alkyl or C1-6alkenyl; R7 is selected from the group consisting of hydrogen, C1-6alkyl, C1-6cycloalkyl, C1-6alkenyl, phenyl, substituted phenyl, napthyl, heteroaryl, substituted heteroaryl, bicycloheteroaryl or substituted bicycloheteroaryl; or NR6R7 together form a saturated 5, 6 or 7 membered ring optionally interrupted by 1, 2, 3 or 4 N, S or O heteroatoms, with the proviso that any two O or S atoms are not bonded to each other; m is an integer selected from the group of 0, 1, 2, 3 or 4; R8 and R9 are selected from a variety of substituents; Z is hydrogen or halogen; novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).(FR) Composés 1,5-benzodiazépines de la formule (I) dans laquelle R1 est choisi parmi alcoyle C1-C6, cycloalcoyle C3-C6, phényle, ou phényle substitué; R2 est choisi parmi alcoyle C3-C6, cycloalcoyle C3-C6, alcényle C3-C6, benzyle, phényle alcoyle C1-C3, ou phényle substitué; ou NR1R2 forment ensemble 1,2,3,4-tétrahydroquinoline ou benzazépine, mono, di ou trisubstituée indépendamment par des substituants alcoyle C1-6, alcoxy C1-6 ou halogène; p est un nombre entier valant 0 ou 1; q est un nombre entier valant 0 ou 1; r est un nombre entier valant 0 ou 1; t est un nombre entier valant 0 ou 1, à condition que lorsque r vaut 0, t vaut également 0; R3, R5 et R6 représentent indépendamment hydrogène ou alcoyle C1-6; R4 représente alcoyle C1-6 ou alcényle C1-6; R7 est choisi parmi le groupe consistant en hydrogène, alcoyle C1-6, cycloalcoyle C1-6, alcényle C1-6, phényle, phényle substitué, naphtyle, hétéroaryle, hétéroaryle substitué, bicyclohétéroaryle ou bicyclohétéroaryle substitué; ou bien NR6R7 forment ensemble un noyau saturé à 5, 6 ou 7 chaînons éventuellement interrompu par 1, 2, 3 ou 4 hétéroatomes de N, S ou O, à la condition que deux atomes quelconques de O ou S ne soient pas liés l'un à l'autre; m est un nombre entier valant 0, 1, 2, 3 ou 4; R8 et R9 sont choisis parmi plusieurs substituants; Z représente hydrogène ou halogène; l'invention concerne également de nouveaux intermédiaires des composés de la formule (I), une composition pharmaceutique destinée à traiter l'obésité, la stase de la vésicule biliaire, les troubles de la sécrétion pancréatique; l'invention concerne encore des procédés de traitement de ces affections ainsi que des procédés de préparation desdits composés.

  1,5-苯并氧化它 cinematic 的化合物（I）的结构式，其中 R1 选自 C1-C6 甲基、C3-C6 深烷基、苯基或苯基取代基；R2 选自 C3-C6 甲基、C3-C6 深烷基、C3-C6 烯基、苯基、苯基 C1-C3 甲基或苯基取代；或 NR1R2 一起构成 1,2,3,4-四氢-quinoline 或苯azepine、单、双、三取代的苯或者其他 C1-6 甲基、C1-6 甲氧基或卤素取代；p、q、r、t 均为0或1整数，且当 r=0 时 t=0；R3、R5 和 R6 为独立之 H 或 C1-6 甲基；R4 为 C1-6 甲基或 C1-6 烯基；R7 选自独立之 H、C1-6 甲基、C1-6 深烷基、C1-6 烯基、苯基、苯基取代、 napthyl、异环、取代的异环、双环-异环或取代的双环-异环；或 NR6R7 一起形成一个饱和的 5、6 或 7 成员环，此环可被 1、2、3 或 4 个 N、S 或 O �eteroatoms 必要时中断，注意其中任何两个 O 或 S 都不能互相连接；m 为 0、1、2、3 或 4 的整数选择；R8 和 R9 选自若干取代基；Z 选自 H 或卤素；该文还涉及了合成这种分子结构（I）的新中间体，用于治疗肥胖症、胆囊结石、胰腺分泌紊乱的医药制剂、该种治疗的方法以及它们的合成工艺。
• CCK OR GASTRIN MODULATING 1,5 BENZODIAZEPINES DERIVATIVES
  申请人：GLAXO WELLCOME INC.

  公开号：EP0755384A1

  公开（公告）日：1997-01-29
• 3-[2-(<i>N</i>-Phenylacetamide)]-1,5-benzodiazepines:  Orally Active, Binding Selective CCK-A Agonists
  作者：Timothy M. Willson、Brad R. Henke、Tanya M. Momtahen、Peter L. Myers、Elizabeth E. Sugg、Rayomand J. Unwalla、Dallas K. Croom、Robert W. Dougherty、Mary K. Grizzle、Michael F. Johnson、Kennedy L. Queen、Thomas J. Rimele、Jeffrey D. Yingling、Michael K. James

  DOI：10.1021/jm960205b

  日期：1996.1.1

  A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in. vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.