N^α-(10,11-dihydroo-5H-dibenz[b.f]azepine-5-carbonyl)toluenesulfonyl-L-arginine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: N^α-(10,11-dihydroo-5H-dibenz[b.f]azepine-5-carbonyl)toluenesulfonyl-L-arginine
• 英文别名: (2S)-2-(5,6-dihydrobenzo[b][1]benzazepine-11-carbonylamino)-5-[[N-(p-tolylsulfonyl)carbamimidoyl]amino]pentanoic acid；(2S)-5-[[amino-[(4-methylphenyl)sulfonylamino]methylidene]amino]-2-(5,6-dihydrobenzo[b][1]benzazepine-11-carbonylamino)pentanoic acid
• 化学式: C₂₈H₃₁N₅O₅S
• 分子量: 549.651
• InChiKey: AIRJBEJQEUOHEG-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苄氧羰基-L-精氨酸 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 丙酮 为溶剂， 反应 26.0h， 生成 N^α-(10,11-dihydroo-5H-dibenz[b.f]azepine-5-carbonyl)toluenesulfonyl-L-arginine
  参考文献：
  名称：

  The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease

  摘要：

  A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 Angstrom with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N-G-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00078-3

文献信息

• The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease
  作者：Earl E Rutenber、James J De Voss、Lucas Hoffman、Robert M Stroud、Kwan H Lee、Juan Alvarez、Fiona McPhee、Charles Craik、Paul R Ortiz de Montellano

  DOI：10.1016/s0968-0896(97)00078-3

  日期：1997.7

  A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 Angstrom with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N-G-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors. (C) 1997 Elsevier Science Ltd.