(S)-4-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-fluorobenzoic acid | 1128075-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-4-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-fluorobenzoic acid
• 英文别名: (S)-4-(1-(Boc)pyrrolidin-2-yl)-2-fluorobenzoic acid；2-fluoro-4-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]benzoic acid
• CAS: 1128075-42-2
• 化学式: C₁₆H₂₀FNO₄
• 分子量: 309.338
• InChiKey: MUXQNPCTAODZDG-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-二氨基苯甲酰胺盐酸盐 、 (S)-4-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-fluorobenzoic acid 在 吡啶 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor

  摘要：

  We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K-i of 1 nM and an EC50 of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.

  DOI：

  10.1021/jm901775y
• 作为产物：
  描述：

  (S)-tert-butyl 2-(3-fluoro-4-(methoxycarbonyl)phenyl)pyrrolidine-1-carboxylate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 (S)-4-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-fluorobenzoic acid
  参考文献：
  名称：

  Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor

  摘要：

  We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K-i of 1 nM and an EC50 of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.

  DOI：

  10.1021/jm901775y

文献信息

• Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (<i>S</i>)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1<i>H</i>-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor
  作者：Thomas D. Penning、Gui-Dong Zhu、Jianchun Gong、Sheela Thomas、Viraj B. Gandhi、Xuesong Liu、Yan Shi、Vered Klinghofer、Eric F. Johnson、Chang H. Park、Elizabeth H. Fry、Cherrie K. Donawho、David J. Frost、Fritz G. Buchanan、Gail T. Bukofzer、Luis E. Rodriguez、Velitchka Bontcheva-Diaz、Jennifer J. Bouska、Donald J. Osterling、Amanda M. Olson、Kennan C. Marsh、Yan Luo、Vincent L. Giranda

  DOI：10.1021/jm901775y

  日期：2010.4.22

  We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K-i of 1 nM and an EC50 of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.