3,4-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one | 78679-18-2

• 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: 3,4-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one
• 英文别名: 3,5-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one；3,5-dimethyl-3,4-dihydro-1H-1,5-benzodiazepin-2-one
• CAS: 78679-18-2
• 化学式: C₁₁H₁₄N₂O
• mdl: MFCD01334031
• 分子量: 190.245
• InChiKey: ZPZUYPYVUSRUHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  355.6±35.0 °C(Predicted)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one 在 tetraphosphorus decasulfide 、 一水合肼 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 2.0h， 生成 (3,5-Dimethyl-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-hydrazine
  参考文献：
  名称：

  2,3-Dihydro-1H-1,5-benzodiazepines: A conversion of thiolactams to amidines

  摘要：

  The synthesis of a new series of diversely N-4 substituted amidines of 2,3-dihydro-1H-1,5-benzodiazepine has been accomplished starting from tetrahydro-1,5-benzodiazepin-2-one derivatives. These compounds were transformed into the desired thiolactams 2a-i which reacted in the presence of mercuric chloride with ammonia, as well as primary or secondary amines to give amidines 3a-i. Hydrazidines 3j-1 were prepared by treatment of thiolactams with an excess of hydrazine.

  DOI：

  10.1007/bf00807260
• 作为产物：
  描述：

  1,3,4,5-四氢-3-甲基-2H-1,5-苯并二氮杂卓-2-酮 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3,4-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one
  参考文献：
  名称：

  Nuclear magnetic resonance spectra of psychotherapeutic agents. V*—conformational analysis of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones

  摘要：

  AbstractThe conformational analysis of biologically active lofendazam (7‐chloro‐5‐phenyl‐1,3,4,5‐tetrahydro‐2H‐1,5‐benzodiazepin‐2‐one) is carried out by means of lanthanide shift reagent assisted 1H NMR spectroscopy: the lanthanide induced shift computer simulation suggests that in deuteriochloroform the heterocyclic ring of lofendazam assumes a cycloheptene‐like chair conformation, where 1‐N moves away from trigonal stereochemistry to a very flattened pyramidal structure. At room temperature the conformational equilibrium is markedly shifted (85%) towards the conformer showing pseudoaxial H‐1 and 5‐Ph. The remarkable influence of steric requirements in controlling conformation, and the importance of 3‐ and/or 4‐methyl groups in hindering the ring inversion at room temperature, have been verified by conformational analysis of suitable analogous 1,3,4,5‐tetraydro‐2H‐1,5‐benzodiazepin‐2‐ones.

  DOI：

  10.1002/mrc.1270150414

文献信息

• NOVEL COMPOUNDS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS
  申请人：Froestl Wolfgang

  公开号：US20100144793A1

  公开（公告）日：2010-06-10

  The present invention relates to compounds of the general formula (I) wherein (formula 2) independently represents a single bond or a double bond, represents a linking group A and A′ are each independently a 5- to 7-membered heterocyclic ring, wherein the heterocyclic rings A und A′ are optionally substituted by one or more substituents, selected from C 1-6 alkyl, C 3-6 cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, C 1-4 alkylene-(optionally substituted phenyl) and C 1-4 alkylene-(optionally substituted heteroaryl), or two substituents may be joined to form an optionally substituted, saturated, unsaturated or aromatic 5- to 7-membered ring which is fused with the heterocyclic ring A or A′, and wherein the heterocyclic rings A und A′ may contain in addition to the units X, X′, Y and Y′ one or more heteroatoms, selected from N, NR, S and Ol wherein R is selected from H and C 1-4 alkyl; the units X and X′ are each independently a H-bond acceptor; and the units Y and Y′ are each independently a H-bond donor. The compound of formula (I) can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system.

  本发明涉及通式（I）的化合物，其中（式2）独立表示单键或双键，表示连接基团A和A'各自独立是5-至7-成员杂环环，其中杂环环A和A'可以选择性地被一个或多个取代基取代，所述取代基可从C1-6烷基，C3-6环烷基，可选择性取代的苯基，可选择性取代的杂环烷基，C1-4烷基烯基（可选择性取代的苯基）和C1-4烷基烯基（可选择性取代的杂环基）中选择，或者两个取代基可以连接形成一个可选择性取代的饱和、不饱和或芳香的5-至7-成员环，其与杂环环A或A'融合，杂环环A和A'除了包含单位X、X'、Y和Y'外，还可以包含一个或多个来自N、NR、S和Ol的杂原子，其中R从H和C1-4烷基中选择；单位X和X'各自独立地是H键受体；单位Y和Y'各自独立地是H键供体。通式（I）的化合物可用于治疗与淀粉样蛋白相关的一类疾病和异常，如阿尔茨海默病，以及与淀粉样蛋白相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织中病理异常/变化相关的眼部疾病。
• Janciene, Regina; Vektariene, Ausra; Mikulskiene, Gema, ARKIVOC, 2013, vol. 2013, # 4, p. 1 - 19
  作者：Janciene, Regina、Vektariene, Ausra、Mikulskiene, Gema、Javorskis, Tomas、Vektaris, Gytis、Klimavicius, Algirdas

  DOI：——

  日期：——
• Bromination of aromatic ring of tetrahydro-1,5-benzodiazepin-2-ones
  作者：B. Puodziunaite、R. Janciene、Z. Stumbreviciute、L. Kosychova

  DOI：10.1007/bf02297679

  日期：2000.6
• 2,3-Dihydro-1H-1,5-benzodiazepines: A conversion of thiolactams to amidines
  作者：B. Puodžiūnaitė、L. Kosychova、R. Jančienė、Z. Stumbrevičiūtė

  DOI：10.1007/bf00807260

  日期：1997.12

  The synthesis of a new series of diversely N-4 substituted amidines of 2,3-dihydro-1H-1,5-benzodiazepine has been accomplished starting from tetrahydro-1,5-benzodiazepin-2-one derivatives. These compounds were transformed into the desired thiolactams 2a-i which reacted in the presence of mercuric chloride with ammonia, as well as primary or secondary amines to give amidines 3a-i. Hydrazidines 3j-1 were prepared by treatment of thiolactams with an excess of hydrazine.
• Nuclear magnetic resonance spectra of psychotherapeutic agents. V*—conformational analysis of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones
  作者：M. C. Aversa、P. Giannetto、G. Romeo、P. Ficarra、M. G. Vigorita

  DOI：10.1002/mrc.1270150414

  日期：1981.4

  AbstractThe conformational analysis of biologically active lofendazam (7‐chloro‐5‐phenyl‐1,3,4,5‐tetrahydro‐2H‐1,5‐benzodiazepin‐2‐one) is carried out by means of lanthanide shift reagent assisted 1H NMR spectroscopy: the lanthanide induced shift computer simulation suggests that in deuteriochloroform the heterocyclic ring of lofendazam assumes a cycloheptene‐like chair conformation, where 1‐N moves away from trigonal stereochemistry to a very flattened pyramidal structure. At room temperature the conformational equilibrium is markedly shifted (85%) towards the conformer showing pseudoaxial H‐1 and 5‐Ph. The remarkable influence of steric requirements in controlling conformation, and the importance of 3‐ and/or 4‐methyl groups in hindering the ring inversion at room temperature, have been verified by conformational analysis of suitable analogous 1,3,4,5‐tetraydro‐2H‐1,5‐benzodiazepin‐2‐ones.