tert-butyl 4-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: tert-butyl 4-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]piperidine-1-carboxylate
• 化学式: C₂₁H₃₀N₂O₃
• 分子量: 358.481
• InChiKey: TVWBZPMRDIDEIG-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]piperidine-1-carboxylate 在 盐酸 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery and Optimization of Potent and CNS Penetrant M₅-Preferring Positive Allosteric Modulators Derived from a Novel, Chiral N-(Indanyl)piperidine Amide Scaffold

  摘要：

  The pharmacology of the M-5 muscarinic acetylcholine receptor (mAChR) is the least understood of the five mAChR subtypes due to a historic lack of selective small molecule tools. To address this shortcoming, we have continued the optimization effort around the prototypical M-5 positive allosteric modulator (PAM) ML380 and have discovered and optimized a new series of M-5 PAMs based on a chiral N-(indanyl)piperidine amide core with robust SAR, human and rat M-5 PAM EC50 values <100 nM and rat brain/plasma K-P values of similar to 0.40. Interestingly, unlike M, and M-4 PAMs with unprecedented mAChR subtype selectivity, this series of M-5 PAMs displayed varying degrees of PAM activity at the other two natively G(q)-coupled mAChRs, M, and M-3, yet were inactive at M-2 and M-4.

  DOI：

  10.1021/acschemneuro.8b00126
• 作为产物：
  描述：

  (R)-(-)-1,2,3,4-四氢-1-萘胺 、 1-Boc-4-哌啶甲酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl 4-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery and Optimization of Potent and CNS Penetrant M₅-Preferring Positive Allosteric Modulators Derived from a Novel, Chiral N-(Indanyl)piperidine Amide Scaffold

  摘要：

  The pharmacology of the M-5 muscarinic acetylcholine receptor (mAChR) is the least understood of the five mAChR subtypes due to a historic lack of selective small molecule tools. To address this shortcoming, we have continued the optimization effort around the prototypical M-5 positive allosteric modulator (PAM) ML380 and have discovered and optimized a new series of M-5 PAMs based on a chiral N-(indanyl)piperidine amide core with robust SAR, human and rat M-5 PAM EC50 values <100 nM and rat brain/plasma K-P values of similar to 0.40. Interestingly, unlike M, and M-4 PAMs with unprecedented mAChR subtype selectivity, this series of M-5 PAMs displayed varying degrees of PAM activity at the other two natively G(q)-coupled mAChRs, M, and M-3, yet were inactive at M-2 and M-4.

  DOI：

  10.1021/acschemneuro.8b00126