3'',3'''-dichloro-5'',5'''-dicarboxy-4'',4'''-di[p-(carboxymethyl)benzyloxy]-4',4'-diphenyl-3β-(3'-buten-1'-yl)cholestane

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3'',3'''-dichloro-5'',5'''-dicarboxy-4'',4'''-di[p-(carboxymethyl)benzyloxy]-4',4'-diphenyl-3β-(3'-buten-1'-yl)cholestane
• 英文别名: 5-[1-[3-carboxy-4-[[4-(carboxymethyl)phenyl]methoxy]-5-chlorophenyl]-4-[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]but-1-enyl]-2-[[4-(carboxymethyl)phenyl]methoxy]-3-chlorobenzoic acid
• 化学式: C₆₃H₇₆Cl₂O₁₀
• 分子量: 1064.2
• InChiKey: QCJIIXGSUOMOPP-YOHDAQLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  18
• 重原子数：
  75
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  铵5-[(Z)-1-(3-羧基-5-氯-4-羟基苯基)-4-[(3S,10S,13R,17R)-10,13-二甲基-17-(6-甲基庚烷-2-基)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-十四氢-1H-环戊二烯并[a]菲-3-基]丁-1-烯基]-3-氯-2-羟基苯甲酸酯 在 potassium cyanide 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 38.0h， 生成 3'',3'''-dichloro-5'',5'''-dicarboxy-4'',4'''-di[p-(carboxymethyl)benzyloxy]-4',4'-diphenyl-3β-(3'-buten-1'-yl)cholestane
  参考文献：
  名称：

  Correlation of Anti-HIV Activity with Anion Spacing in a Series of Cosalane Analogues with Extended Polycarboxylate Pharmacophores

  摘要：

  Cosalane and its synthetic derivatives inhibit the binding of gp120 to CD4 as well as the fusion of the viral envelope with the cell membrane. The binding of the cosalanes to CD4 is proposed to involve ionic interactions of the negatively charged carboxylates of the ligands with positively charged arginine and lysine amino acid side chains of the protein. To investigate the effect of anion spacing on anti-HIV activity in the cosalane system, a series of cosalane tetracarboxylates was synthesized in which the two proximal and two distal carboxylates are separated by 6-12 atoms. Maximum activity was observed when the proximal and distal carboxylates are separated by 8 atoms. In a series of cosalane amino acid derivatives containing glutamic acid, glycine, aspartic acid, beta -alanine, leucine, and phenylalanine residues, maximum activity was displayed by the di(glutamic acid) analogue. A hypothetical model has been devised for the binding of the cosalane di(glutamic acid) conjugate to CD4. In general, the compounds in this series are more potent against HIV-1(RF) in CEM-SS cells than they are vs HIV-1(IIIB) in MT-4 cells, and they are least potent vs HIV-2(ROD) in MT-4 cells.

  DOI：

  10.1021/jm000290u

文献信息

• Correlation of Anti-HIV Activity with Anion Spacing in a Series of Cosalane Analogues with Extended Polycarboxylate Pharmacophores
  作者：Kalpathy C. Santhosh、Gitendra C. Paul、Erik De Clercq、Christophe Pannecouque、Myriam Witvrouw、Tracy L. Loftus、Jim A. Turpin、Robert W. Buckheit,、Mark Cushman

  DOI：10.1021/jm000290u

  日期：2001.3.1

  Cosalane and its synthetic derivatives inhibit the binding of gp120 to CD4 as well as the fusion of the viral envelope with the cell membrane. The binding of the cosalanes to CD4 is proposed to involve ionic interactions of the negatively charged carboxylates of the ligands with positively charged arginine and lysine amino acid side chains of the protein. To investigate the effect of anion spacing on anti-HIV activity in the cosalane system, a series of cosalane tetracarboxylates was synthesized in which the two proximal and two distal carboxylates are separated by 6-12 atoms. Maximum activity was observed when the proximal and distal carboxylates are separated by 8 atoms. In a series of cosalane amino acid derivatives containing glutamic acid, glycine, aspartic acid, beta -alanine, leucine, and phenylalanine residues, maximum activity was displayed by the di(glutamic acid) analogue. A hypothetical model has been devised for the binding of the cosalane di(glutamic acid) conjugate to CD4. In general, the compounds in this series are more potent against HIV-1(RF) in CEM-SS cells than they are vs HIV-1(IIIB) in MT-4 cells, and they are least potent vs HIV-2(ROD) in MT-4 cells.