Trifluoro-methanesulfonic acid 1-(bis-benzyloxy-phosphoryl)-propyl ester | 133859-21-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: Trifluoro-methanesulfonic acid 1-(bis-benzyloxy-phosphoryl)-propyl ester
• 英文别名: 1-Bis(phenylmethoxy)phosphorylpropyl trifluoromethanesulfonate
• CAS: 133859-21-9
• 化学式: C₁₈H₂₀F₃O₆PS
• 分子量: 452.388
• InChiKey: FYWRVCHELVQSBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Trifluoro-methanesulfonic acid 1-(bis-benzyloxy-phosphoryl)-propyl ester 在 sodium hydroxide 、 potassium carbonate 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 66.0h， 生成 {(R)-1-[(S)-1-((S)-5-Benzyloxycarbonylamino-1-methylcarbamoyl-pentylcarbamoyl)-3-methyl-butylamino]-propyl}-phosphonic acid dibenzyl ester
  参考文献：
  名称：

  Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase

  摘要：

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).

  DOI：

  10.1021/jm00027a020
• 作为产物：
  描述：

  亚磷酸二苄酯 在 2,6-二甲基吡啶 、 aluminum oxide 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 Trifluoro-methanesulfonic acid 1-(bis-benzyloxy-phosphoryl)-propyl ester
  参考文献：
  名称：

  Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase

  摘要：

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).

  DOI：

  10.1021/jm00027a020

文献信息

• PHOSPHONOPEPTIDES WITH COLLAGENASE INHIBITING ACTIVITY
  申请人：Beecham Group p.l.c.

  公开号：EP0527761A1

  公开（公告）日：1993-02-24
• [EN] PHOSPHONOPEPTIDES WITH COLLAGENASE INHIBITING ACTIVITY
  申请人：BEECHAM GROUP PLC

  公开号：WO1991015506A1

  公开（公告）日：1991-10-17

  (EN) Azalactam derivatives processes for their preparation and their use as collagenase inhibitors having structure (I).(FR) Dérivés d'azalactame, procédés servant à leur préparation et utilisation comme inhibiteurs de collagénase, ayant le formule (I).
• Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase
  作者：John Bird、Rachel C. De Mello、Gregory P. Harper、David J. Hunter、Eric H. Karran、Roger E. Markwell、Anette J. Miles-Williams、Shahzad S. Rahman、Robert W. Ward

  DOI：10.1021/jm00027a020

  日期：1994.1

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).