3-[[5-chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-(3H)-one | 202822-96-6

• 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-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-(3H)-one
• 英文别名: 3-[[5-Chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one；3-[[5-chloro-2-methoxy-4-(2-oxo-1H-imidazol-3-yl)phenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one
• CAS: 202822-96-6
• 化学式: C₂₀H₁₄ClF₃N₄O₄
• 分子量: 466.804
• InChiKey: BCQSMUJTOGJEJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  83.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-[[5-chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-(3H)-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 3-[[5-Chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-hydroxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one
  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：

  在 甲酸 作用下， 反应 18.0h， 以850 mg的产率得到3-[[5-chloro-4-(2,3-dihydro-2-oxo-1H-imidazol-1-yl)-2-methoxyphenyl]-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-(3H)-one
  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

文献信息

• Diphenyl oxadiazolones as potassium channel modulators
  申请人：Bristol-Myers Squibb Company

  公开号：US05869509A1

  公开（公告）日：1999-02-09

  Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: ##STR1## wherein "Het" is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; R.sup.a, R.sup.b and R.sup.c each are independently selected from hydrogen, halogen, OH, CF.sub.3, ##STR2## provided R.sup.c is not hydrogen; and when R.sup.a and R.sup.b are hydrogen, R.sup.c may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol- 2-yl, and pyridinyl; R.sup.d and R.sup.e each are independently selected from hydrogen, halogen, CF.sub.3, NO.sub.2 or imidazol-1-yl; m, n and p each are independently selected from an integer of O or 1; and R.sup.f and R.sup.g each are independently hydrogen; C.sub.1-4 alkyl; or R.sup.f and R.sup.g, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

  公式1的新化合物可用于治疗对大导电钙激活钾通道开放剂敏感的疾病：其中"Het"是一组选择的杂环基团之一；Z独立于每次出现，选自O或S；R.sup.a、R.sup.b和R.sup.c各自独立地选自氢、卤素、OH、CF.sub.3、##STR2##，只要R.sup.c不是氢；当R.sup.a和R.sup.b为氢时，R.sup.c可以是从咪唑-1-基、吗啉甲基、N-甲基咪唑-2-基和吡啶基组成的杂环基团之一；R.sup.d和R.sup.e各自独立地选自氢、卤素、CF.sub.3、NO.sub.2或咪唑-1-基；m、n和p各自独立地选自O或1的整数；而R.sup.f和R.sup.g各自独立地是氢、C.sub.1-4烷基；或者R.sup.f和R.sup.g与它们所附着的氮原子一起，是从N-甲基哌嗪、吗啉、硫代吗啉、N-苄基哌嗪和咪唑啉酮组成的杂环基团之一。
• US6077861A
  申请人：——

  公开号：US6077861A

  公开（公告）日：2000-06-20
• US6271249B1
  申请人：——

  公开号：US6271249B1

  公开（公告）日：2001-08-07