[(S)-((1S,2S)-2-Azidomethyl-cyclopropyl)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-methyl]-carbamic acid benzyl ester | 561324-07-0

• 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: [(S)-((1S,2S)-2-Azidomethyl-cyclopropyl)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-methyl]-carbamic acid benzyl ester
• CAS: 561324-07-0
• 化学式: C₁₉H₂₄N₄O₅
• 分子量: 388.423
• InChiKey: XBFVAALMXDDDBQ-GFMKDAKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  114.78
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  [(S)-((1S,2S)-2-Azidomethyl-cyclopropyl)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-methyl]-carbamic acid benzyl ester 在 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 35.0h， 生成 [(S)-[(1S,2S)-2-(Acetimidoylamino-methyl)-cyclopropyl]-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-methyl]-carbamic acid benzyl ester; hydrobromide
  参考文献：
  名称：

  Synthesis and evaluation of trans 3,4-cyclopropyl l-arginine analogues as isoform selective inhibitors of nitric oxide synthase

  摘要：

  Four optically pure conformationally restricted L-arginine analogues syn-1 and anti- 2 trans- 3,4-cyclopropyl L-arginine, and syn-3 and anti- trans- 3,4-cyclopropyl N-(1-iminoethyl) L-ornithine 4 were synthesized. These compounds were tested as potential inhibitors against the three isoforms of nitric oxide synthase (NOS). Compound I was determined to be a poor substrate of NOS, while compound 2 was determined to be a poor mixed type inhibitor and did not exhibit any isoform selectivity. Syn- 3 and anti- trans- 3,4-cyclopropyl N-(I-iminoethyl) L-ornithine 4 were found to be competitive inhibitors of NOS. These compounds were time dependent inhibitors of inducible NOS (iNOS), but not of neuronal NOS (nNOS) or endothelial NOS (eNOS). Compound 3 was 10- to 100-fold more potent an inhibitor than 4, exhibited a 5-fold increase in nNOS/iNOS and eNOS/iNOS selectivity over 4, and displayed tight binding characteristics against iNOS. These results indicate that the relative configuration of the cyclopropyl ring in the L-arginine analogues significantly affects their inhibitory potential and NOS isoform selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00554-0
• 作为产物：
  描述：

  [(S)-((1S,2S)-2-Hydroxymethyl-cyclopropyl)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-methyl]-carbamic acid benzyl ester 在 迭氮酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 苯 为溶剂， 以85%的产率得到[(S)-((1S,2S)-2-Azidomethyl-cyclopropyl)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-methyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Synthesis and evaluation of trans 3,4-cyclopropyl l-arginine analogues as isoform selective inhibitors of nitric oxide synthase

  摘要：

  Four optically pure conformationally restricted L-arginine analogues syn-1 and anti- 2 trans- 3,4-cyclopropyl L-arginine, and syn-3 and anti- trans- 3,4-cyclopropyl N-(1-iminoethyl) L-ornithine 4 were synthesized. These compounds were tested as potential inhibitors against the three isoforms of nitric oxide synthase (NOS). Compound I was determined to be a poor substrate of NOS, while compound 2 was determined to be a poor mixed type inhibitor and did not exhibit any isoform selectivity. Syn- 3 and anti- trans- 3,4-cyclopropyl N-(I-iminoethyl) L-ornithine 4 were found to be competitive inhibitors of NOS. These compounds were time dependent inhibitors of inducible NOS (iNOS), but not of neuronal NOS (nNOS) or endothelial NOS (eNOS). Compound 3 was 10- to 100-fold more potent an inhibitor than 4, exhibited a 5-fold increase in nNOS/iNOS and eNOS/iNOS selectivity over 4, and displayed tight binding characteristics against iNOS. These results indicate that the relative configuration of the cyclopropyl ring in the L-arginine analogues significantly affects their inhibitory potential and NOS isoform selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00554-0