3-[(5-Chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl)-phenyl]-1,3,4-oxadiazol-2(3H)-one | 202822-68-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[(5-Chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl)-phenyl]-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 3-(5-chloro-2-methoxybenzyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one；3-[(5-chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one
• CAS: 202822-68-2
• 化学式: C₁₇H₁₂ClF₃N₂O₃
• 分子量: 384.742
• InChiKey: AYUHREFIMUIAMC-UHFFFAOYSA-N

物化性质

• 熔点：
  144-145 °C
• 沸点：
  427.0±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[(5-Chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl)-phenyl]-1,3,4-oxadiazol-2(3H)-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 60.0h， 以77%的产率得到3-[(5-chloro-2-methoxyphenyl)methyl]-5-[(4-trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-(3H)-thione
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n
• 作为产物：
  描述：

  5-氯-2-甲氧苄基醇 在 三聚氯氰 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 22.0h， 生成 3-[(5-Chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl)-phenyl]-1,3,4-oxadiazol-2(3H)-one
  参考文献：
  名称：

  一种BMS-191011的合成方法

  摘要：

  本发明涉及一种BMS‑191011化合物的合成方法。该方法以4‑三氟甲基苯甲酰肼作为原料经氧化羰基化，甲基保护，卤化，胺化和脱保护等步骤制得BMS‑191011。本发明采用CO气球代替光气，降低了反应的毒性，增加了反应的可操作性。该方法具有原料简单易得，反应条件温和，操作工艺简洁的特点。

  公开号：

  CN104710379B

文献信息

• Phosphate derivatives of diaryl 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US05939405A1

  公开（公告）日：1999-08-17

  The present invention provides novel phosphate derivatives having the general formula wherein A, R.sup.1 and R.sup.2 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of potassium channels.

  本发明提供了具有一般式的新型磷酸盐衍生物，其中A、R^1和R^2如本文所定义，或其无毒的药用可接受盐或溶剂，可用于治疗对钾通道开放有响应的疾病。
• Amino acid derivatives of diaryl 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US05977150A1

  公开（公告）日：1999-11-02

  The present invention provides novel amino acid derivatives having the general formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of potassium channels.

  本发明提供了具有一般式##STR1##的新型氨基酸衍生物，其中R.sup.1、R.sup.2和R.sup.3如本文所定义，或其无毒药学上可接受的盐或溶剂，用于治疗对钾通道开放有响应的疾病。
• Derivatives of 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US06034113A1

  公开（公告）日：2000-03-07

  The present invention provides novel oxadiazolone derivatives having the general formula ##STR1## wherein A, B, D and R are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of the large conductance calcium-activated potassium channels.

  本发明提供了一种新型的噁唑烷酮衍生物，其具有以下一般式：##STR1## 其中A、B、D和R如本文所定义，或其无毒药学上可接受的盐或溶剂，可用于治疗对大导电钙激活钾通道开放有响应的疾病。
• Carbamate derivatives of diaryl 1,3,4-oxadiazolone
  申请人：Bristol-Myers Squibb Company

  公开号：US06162817A1

  公开（公告）日：2000-12-19

  The present invention provides novel carbamate oxadiazolone derivatives having the general formula ##STR1## wherein R.sup.1 and R.sup.2 are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of the large conductance calcium-activated potassium channels.

  本发明提供了具有通式 ##STR1## 的新型碳酸酯噁二唑酮衍生物，其中 R.sup.1 和 R.sup.2 如本文所定义，或其无毒药学上可接受的盐或溶剂，可用于治疗对大导电性钙激活钾通道的开放具有响应的疾病。
• [EN] DERIVATIVES OF 1,3,4-OXADIAZOLONE<br/>[FR] DERIVES BENZOATE DE 1,3,4-OXADIAZOLONE
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1999038510A1

  公开（公告）日：1999-08-05

  (EN) The present invention provides novel oxadiazolone derivatives having general formula (I), wherein A, B, D and R are as defined herein, or a nontoxic pharmaceutically acceptable salt or solvate thereof and are useful in the treatment of disorders which are responsive to the opening of the large conductance calcium-activated potassium channels.(FR) Cette invention, qui a trait à de nouveaux dérivés benzoate correspondant à la formule générale: dans laquelle A, B, D et R sont tels que définis dans le descriptif, concerne également un sel ou un solvate, non toxique et acceptable du point de vue pharmaceutique, de ces dérivés. Ces substances sont efficaces dans le cadre du traitement d'affections influencées par l'ouverture des canaux potassium à importante conductance activés par le calcium.

  (EN) 本发明提供了具有一般式（I）的新型噁唑酮衍生物，其中A、B、D和R如本文所定义，或其无毒药学上可接受的盐或溶剂，在治疗对大电导钙激活钾通道开放有反应的疾病方面具有用处。 (FR) 本发明提供了新的苯甲酸酯衍生物，其通式如下：其中A、B、D和R如本文所定义，或其无毒药学上可接受的盐或溶剂，可用于治疗对开放大电导钙激活钾通道有反应的疾病。