10-chloro-2t,7-dimethyl-11b-phenyl-(11br)-2,3,7,11b-hexahydro-benzo[f]oxazolo[3,2-e][1,4]diazepin-6-one | 24111-48-6

• 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: 10-chloro-2t,7-dimethyl-11b-phenyl-(11br)-2,3,7,11b-hexahydro-benzo[f]oxazolo[3,2-e][1,4]diazepin-6-one
• 英文别名: 10-chloro-2,7-dimethyl-2,3,5,11b-tetrahydro-11b-phenyloxazolo[3,2-d] [1,4]benzodiazepin-6(7h)-one；10-chloro-2,7-dimethyl-2,3,5,11b-tetrahydro-11b-phenyloxazolo[3,2-d][1,4]benzodiazepin-6(7H)-one；10-chloro-2,7-dimethyl-11b-phenyl-3,5-dihydro-2H-[1,3]oxazolo[3,2-d][1,4]benzodiazepin-6-one
• CAS: 24111-48-6
• 化学式: C₁₉H₁₉ClN₂O₂
• 分子量: 342.825
• InChiKey: RGTAMTZPLZALGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  10-chloro-2t,7-dimethyl-11b-phenyl-(11br)-2,3,7,11b-hexahydro-benzo[f]oxazolo[3,2-e][1,4]diazepin-6-one 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  The acid-base equilibrium reaction of benzodiazepinooxazoles.

  摘要：

  研究了恶唑仑（10-氯-2, 3, 5, 6, 7, 11b-hexahydro-2-methyl-11b-phenylbenzo [6, 7]-1, 4-diazepino [5, 4-b] oxazol-6-one）和 1, 4-苯并二氮杂卓（BDOZ）的 13 种其他衍生物的酸碱平衡反应。研究采用紫外吸收光谱和荧光光谱来获得平衡常数。在大多数 BDOZ 中，质子化的物质会在与二氮杂卓核融合的恶唑烷环上迅速裂解，并与原始物质达到平衡。少数特殊化合物的平衡需要明显的时间差。从物理有机化学的角度讨论了取代基对 pKa 值的影响。

  DOI：

  10.1248/cpb.30.3810
• 作为产物：
  描述：

  地西泮 在 三氯化铝 作用下， 以 正己烷 、 methyloxirane 、 苯 为溶剂， 生成 10-chloro-2t,7-dimethyl-11b-phenyl-(11br)-2,3,7,11b-hexahydro-benzo[f]oxazolo[3,2-e][1,4]diazepin-6-one
  参考文献：
  名称：

  Intermediates for tricyclic benzodiazepines

  摘要：

  描述了在三环苯二氮卓衍生物（“A”）中，1位位置带有一个氢氧基较低的烷基取代基，以及在苯二氮卓基团的4位和5位之间连接的杂环环。该杂环环将包含出现在苯二氮卓环的4位的氮原子，以及连接到苯二氮卓环5位的碳原子上的杂原子，该杂原子可能是氧或氮。“A”中带有新杂环环中的氧原子可以通过在酸催化剂存在下用环氧化合物处理相应的4,5-不饱和苯二氮卓制备而成。“A”中带有新杂环环中的氮或氧原子可以通过对应开放化合物的环化制备而成。“A”可用作镇静剂、肌肉松弛剂和抗惊厥剂。

  公开号：

  US03965151A1

文献信息

• Studies on Benzodiazepinooxazoles. III. Reactions and Rearrangements of Benzo [6, 7]-1, 4-diazepino-[5, 4-<I>b</I>] oxazole Derivatives
  作者：ATSUSUKE TERADA、YUICHIRO YABE、TETSUO MIYADERA、RYUJI TACHIKAWA

  DOI：10.1248/cpb.21.742

  日期：——

  Treatment of 10-halogeno-2, 3, 5, 6, 7, 11b -hexahydro -7-methyl-11b-phenylbenzo [6, 7]-1, 4-diazepino [5, 4-b] oxazol-6-one (IIIa-d) with dimethyl formamide in the presence of sodium hydride gave exo -methylene compounds (Va-d). On the other hand, the compounds (IIIe-g) having halogen at o-position of the 11b-phenyl group gave no exomethylene compounds, but isoindoles (XVIIIe-g) and acridanone derivatives (XIXe-g). A mechanistic assumption for the formation of these compounds from benzo [6, 7]-1, 4-diazepino [5, 4-b] oxazole derivatives was given.

  在氢化钠存在下，用二甲基甲酰胺处理 10-卤代-2，3，5，6，7，11b-六氢-7-甲基-11b-苯基苯并[6，7]-1，4-二氮杂卓[5，4-b]恶唑-6-酮（IIIa-d），可得到外亚甲基化合物（Va-d）。另一方面，11b-苯基的 o 位上有卤素的化合物（IIIe-g）没有生成外亚甲基化合物，但生成了异吲哚（XVIIIe-g）和吖啶酮衍生物（XIXe-g）。对这些化合物从苯并 [6，7]-1，4-二氮杂卓 [5，4-b] 恶唑衍生物中生成的机理进行了假设。
• Intermediates for the production of tricyclic benzodiazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04017531A1

  公开（公告）日：1977-04-12

  Tricyclic benzodiazepine derivatives ("A") bearing a hydroxylower alkyl substituent in the 1-position and a heterocyclic ring joined between positions 4 and 5 of the benzodiazepine moiety are described. The heterocyclic ring will contain the nitrogen atom appearing at position 4 of the benzodiazepine ring as well as the hetero atom, which may be either oxygen or nitrogen, attached to the carbon atom at the 5-position of the benzodiazepine ring. A bearing an oxygen atom in the new heterocyclic ring may be formed from the corresponding 4,5-unsaturated benzodiazepines by treatment with an epoxide compound in the presence of an acid catalyst. A bearing either a nitrogen or an oxygen atom in the new heterocyclic ring may be prepared by cyclization of the corresponding open compound. A are useful as sedative, muscle relaxant and anti-convulsant agents.

  本文描述了三环苯二氮平衍生物（“A”），其在1位具有一个羟基较低烷基取代基，并且在苯二氮平骨架的4和5位之间连接了一个杂环环。杂环环将包含出现在苯二氮平环的4位的氮原子，以及连接到苯二氮平环的5位碳原子上的杂原子，可以是氧原子或氮原子。在存在酸催化剂的情况下，通过用环氧化合物处理相应的4,5-不饱和苯二氮平来形成在新杂环环中具有氧原子的A。通过环化相应的开放化合物来制备在新杂环环中具有氮原子或氧原子的A。A可用作镇静剂、肌肉松弛剂和抗惊厥剂。
• Anxiolytic sedatives. 1. Synthesis and pharmacology of benzo[6,7]-1,4-diazepino[5,4-b]oxazole derivatives and analogs
  作者：Ryuji Tachikawa、Tetsuo Miyadera、Atsusuke Terada、Mitsunobu Fukunaga、Yoichi Kawano、Toshiharu Kamioka、Chihiro Tamura、Hiromu Takagi

  DOI：10.1021/jm00288a015

  日期：1971.6
• Multi-API Loading Prodrugs
  申请人：Zeidan Tarek A.

  公开号：US20120202823A1

  公开（公告）日：2012-08-09

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.
• MULTI-API LOADING PRODRUGS
  申请人：Alkermes Pharma Ireland Limited

  公开号：US20180194732A1

  公开（公告）日：2018-07-12

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.