methyl 6,7-dihydro-5[H]-cyclopenta[c]pyridine-7-carboxylate | 154618-37-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 6,7-dihydro-5[H]-cyclopenta[c]pyridine-7-carboxylate
• 英文别名: methyl5H,6H,7H-cyclopenta[c]pyridine-7-carboxylate；methyl 6,7-dihydro-5H-cyclopenta[c]pyridine-7-carboxylate
• CAS: 154618-37-8
• 化学式: C₁₀H₁₁NO₂
• 分子量: 177.203
• InChiKey: BWLFVHLVSVJGMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 6,7-dihydro-5[H]-cyclopenta[c]pyridine-7-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 6,7-dihydro-5H-cyclopenta[c]pyridine-7-carboxylic acid
  参考文献：
  名称：

  Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies

  摘要：

  The complex formed from crystallization of human farnesyl pyrophosphate synthase (hFPPS) from a solution of racemic [ 6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501,8), a chiral analog of the anti-osteoporotic drug risedronate, contained the R enantiomer in the enzyme active site. This enantiospecificity was assessed by computer modeling of inhibitor-active site interactions using Autodock 3, which was also evaluated for predictive ability in calculations of the known configurations of risedronate, zoledronate, and minodronate complexed in the active site of hFPPS. In comparison with these structures, the 8 complex exhibited certain differences, including the presence of only one Mg2+, which could contribute to its 100-fold higher IC50. An improved synthesis of 8 is described, which decreases the number of steps from 12 to 8 and increases the overall yield by 17-fold. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.088
• 作为产物：
  描述：

  methyl 7[H]-cyclopenta[c]pyridine-7-carboxylate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以70%的产率得到methyl 6,7-dihydro-5[H]-cyclopenta[c]pyridine-7-carboxylate
  参考文献：
  名称：

  Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies

  摘要：

  The complex formed from crystallization of human farnesyl pyrophosphate synthase (hFPPS) from a solution of racemic [ 6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501,8), a chiral analog of the anti-osteoporotic drug risedronate, contained the R enantiomer in the enzyme active site. This enantiospecificity was assessed by computer modeling of inhibitor-active site interactions using Autodock 3, which was also evaluated for predictive ability in calculations of the known configurations of risedronate, zoledronate, and minodronate complexed in the active site of hFPPS. In comparison with these structures, the 8 complex exhibited certain differences, including the presence of only one Mg2+, which could contribute to its 100-fold higher IC50. An improved synthesis of 8 is described, which decreases the number of steps from 12 to 8 and increases the overall yield by 17-fold. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.088

文献信息

• Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies
  作者：Sylvine Deprèle、Boris A. Kashemirov、James M. Hogan、Frank H. Ebetino、Bobby L. Barnett、Artem Evdokimov、Charles E. McKenna

  DOI：10.1016/j.bmcl.2008.03.088

  日期：2008.5

  The complex formed from crystallization of human farnesyl pyrophosphate synthase (hFPPS) from a solution of racemic [ 6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501,8), a chiral analog of the anti-osteoporotic drug risedronate, contained the R enantiomer in the enzyme active site. This enantiospecificity was assessed by computer modeling of inhibitor-active site interactions using Autodock 3, which was also evaluated for predictive ability in calculations of the known configurations of risedronate, zoledronate, and minodronate complexed in the active site of hFPPS. In comparison with these structures, the 8 complex exhibited certain differences, including the presence of only one Mg2+, which could contribute to its 100-fold higher IC50. An improved synthesis of 8 is described, which decreases the number of steps from 12 to 8 and increases the overall yield by 17-fold. (c) 2008 Elsevier Ltd. All rights reserved.