1-[(4R)-2,2-dimethyl-1,3-dioxolane-4-methyl]-3-{[(1S,3R,6S)-2,1'-spirocyclopropane(bicyclo[2.2.1]heptane)-1'-norbornylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one | 1173088-98-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1-[(4R)-2,2-dimethyl-1,3-dioxolane-4-methyl]-3-{[(1S,3R,6S)-2,1'-spirocyclopropane(bicyclo[2.2.1]heptane)-1'-norbornylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
• 英文别名: 1-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-3-[1-[[(1S,2S,4R)-spiro[bicyclo[2.2.1]heptane-3,1'-cyclopropane]-2-yl]methyl]piperidin-4-yl]benzimidazol-2-one
• CAS: 1173088-98-6
• 化学式: C₂₈H₃₉N₃O₃
• 分子量: 465.636
• InChiKey: HJVZZHPEJZCMGC-MQFRRQCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  45.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(4R)-2,2-dimethyl-1,3-dioxolane-4-methyl]-3-{[(1S,3R,6S)-2,1'-spirocyclopropane(bicyclo[2.2.1]heptane)-1'-norbornylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以61%的产率得到1-[(2R)-2,3-dihydroxypropyl]-3-{[(1S,3R,6S)-2,1'-spirocyclopropane(bicyclo[2.2.1]heptane)-1'-norbornylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one hydrochloride
  参考文献：
  名称：

  Identification of an Orally Active Opioid Receptor-like 1 (ORL1) Receptor Antagonist 4-{3-[(2R)-2,3-Dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1′-cyclopropan]-3-ylmethyl]piperidine as Clinical Candidate

  摘要：

  Our efforts to optimize prototype opioid receptor-like I (ORL1) antagonist 1 led to the discovery of 4-{3-[(2R)-2, 3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine 10. 10 showed potent ORL1 antagonistic activity, excellent selectivity over other opioid receptors, and in vivo efficacy after oral dosing. Currently clinical trials of 10 are underway.

  DOI：

  10.1021/jm900581g
• 作为产物：
  描述：

  1-{[(1S,3R,6S)-2,1'-spirocyclopropane(bicyclo[2.2.1]heptane)-1'-norbornylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one 、 (R)-(-)-对甲基苯磺酸-2,2-二甲基-1,3-二氧戊环基-4-甲酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 以73%的产率得到1-[(4R)-2,2-dimethyl-1,3-dioxolane-4-methyl]-3-{[(1S,3R,6S)-2,1'-spirocyclopropane(bicyclo[2.2.1]heptane)-1'-norbornylmethyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  Identification of an Orally Active Opioid Receptor-like 1 (ORL1) Receptor Antagonist 4-{3-[(2R)-2,3-Dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1′-cyclopropan]-3-ylmethyl]piperidine as Clinical Candidate

  摘要：

  Our efforts to optimize prototype opioid receptor-like I (ORL1) antagonist 1 led to the discovery of 4-{3-[(2R)-2, 3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine 10. 10 showed potent ORL1 antagonistic activity, excellent selectivity over other opioid receptors, and in vivo efficacy after oral dosing. Currently clinical trials of 10 are underway.

  DOI：

  10.1021/jm900581g

文献信息

• Identification of an Orally Active Opioid Receptor-like 1 (ORL1) Receptor Antagonist 4-{3-[(2<i>R</i>)-2,3-Dihydroxypropyl]-2-oxo-2,3-dihydro-1<i>H</i>-benzimidazol-1-yl}-1-[(1<i>S</i>,3<i>S</i>,4<i>R</i>)-spiro[bicyclo[2.2.1]heptane-2,1′-cyclopropan]-3-ylmethyl]piperidine as Clinical Candidate
  作者：Atsushi Satoh、Takeshi Sagara、Hiroki Sakoh、Masaya Hashimoto、Hiroshi Nakashima、Tetsuya Kato、Yasuhiro Goto、Sayaka Mizutani、Tomoko Azuma-Kanoh、Takeshi Tani、Shoki Okuda、Osamu Okamoto、Satoshi Ozaki、Yoshikazu Iwasawa、Hisashi Ohta、Hiroshi Kawamoto

  DOI：10.1021/jm900581g

  日期：2009.7.23

  Our efforts to optimize prototype opioid receptor-like I (ORL1) antagonist 1 led to the discovery of 4-3-[(2R)-2, 3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine 10. 10 showed potent ORL1 antagonistic activity, excellent selectivity over other opioid receptors, and in vivo efficacy after oral dosing. Currently clinical trials of 10 are underway.