2-benzyloxy-3-octadecyloxypropyl 4-trimethylammoniobutyl phosphate | 108003-46-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 英文名称: 2-benzyloxy-3-octadecyloxypropyl 4-trimethylammoniobutyl phosphate
• 英文别名: (3-octadecoxy-2-phenylmethoxypropyl) 4-(trimethylazaniumyl)butyl phosphate
• CAS: 108003-46-9
• 化学式: C₃₅H₆₆NO₆P
• 分子量: 627.886
• InChiKey: GWIYEEUGKSINNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.84
• 重原子数：
  43.0
• 可旋转键数：
  31.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  77.05
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-benzyloxy-3-octadecyloxypropyl 4-trimethylammoniobutyl phosphate 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 23.0h， 生成 (2-Acetyloxy-3-octadecoxypropyl) 4-(trimethylazaniumyl)butyl phosphate
  参考文献：
  名称：

  Analogs of platelet activating factor. 4. Some modifications of the phosphocholine moiety

  摘要：

  Racemic analogues of platelet activating factor (PAF) in which the methylene bridge separating the phosphate and trimethylammonium moieties is altered in length (7a-f) have been prepared. Increasing the length of this bridge results in a progressive decrease in the hypotensive and platelet aggregation responses. Analogues in which the phosphocholine group is substituted with a methyl group (7h and 7i) or a phenyl group (5j) or in which the methylene bridge is replaced with a meta-substituted benzyl group (5k) have been prepared. With respect to both the blood pressure and platelet aggregation responses, 7i and 5k showed little if any changes in potency compared to racemic C16-PAF (1a). While 7h is more potent than 1a with respect to both the hypotensive and platelet aggregation properties, 5j is less potent. Replacement of the phosphate moiety of C18-PAF (1b) with a phosphonate group (7g) leads to decreased activity in both assays. Analogue 11, in which the phosphocholine group has been replaced with a 4-(trimethylammonio)butoxy group, exhibited no detectable hypotensive or platelet aggregating activity. None of the analogues exhibited a separation of the blood pressure and platelet aggregation activities.

  DOI：

  10.1021/jm00153a005
• 作为产物：
  描述：

  1-O-octadecyl-2-O-benzylglycerol 在 sodium acetate 、 三乙胺 作用下， 以 四氢呋喃 、 四氯化碳 、 氯仿 、 乙腈 为溶剂， 反应 21.5h， 生成 2-benzyloxy-3-octadecyloxypropyl 4-trimethylammoniobutyl phosphate
  参考文献：
  名称：

  Analogs of platelet activating factor. 4. Some modifications of the phosphocholine moiety

  摘要：

  Racemic analogues of platelet activating factor (PAF) in which the methylene bridge separating the phosphate and trimethylammonium moieties is altered in length (7a-f) have been prepared. Increasing the length of this bridge results in a progressive decrease in the hypotensive and platelet aggregation responses. Analogues in which the phosphocholine group is substituted with a methyl group (7h and 7i) or a phenyl group (5j) or in which the methylene bridge is replaced with a meta-substituted benzyl group (5k) have been prepared. With respect to both the blood pressure and platelet aggregation responses, 7i and 5k showed little if any changes in potency compared to racemic C16-PAF (1a). While 7h is more potent than 1a with respect to both the hypotensive and platelet aggregation properties, 5j is less potent. Replacement of the phosphate moiety of C18-PAF (1b) with a phosphonate group (7g) leads to decreased activity in both assays. Analogue 11, in which the phosphocholine group has been replaced with a 4-(trimethylammonio)butoxy group, exhibited no detectable hypotensive or platelet aggregating activity. None of the analogues exhibited a separation of the blood pressure and platelet aggregation activities.

  DOI：

  10.1021/jm00153a005

文献信息

• Synthesis and antitumor activity of new alkylphospholipids containing modifications of the phosphocholine moiety.
  作者：Kiyoshi UKAWA、Eiko IMAMIYA、Hiroaki YAMAMOTO、Katsutoshi MIZUNO、Akihiro TASAKA、Zen-ichi TERASHITA、Tetsuya OKUTANI、Hiroaki NOMURA、Takashi KASUKABE、Motoo HOZUMI、Ichiro KUDO、Keizo INOUE

  DOI：10.1248/cpb.37.1249

  日期：——

  New antitumor alkylglycerophospholipids, in which primarily the phosphocholine moiety of the platelet activating factor (PAF) molecule was modified, were synthesized from 1-alkyl-2-substituted glycerols by introducing polar head phosphoryl groups having methylene bridges of various lengths (from 2 to 14 carbons). They were tested for PAF agonistic activity and antitumor properties. In a series of 1-octadecyl-2-acetoacetylglycerophospholipids (1a-f), an increase in the length of the methylene bridge separating the phosphate and trimethylammonio group in the polar head side chain at position 3 of the glycerol backbone resulted in a progressive decrease in PAF agonistic activity and a characteristic change in antitumor activity against human promyelocytic leukemia cells (HL-60). Maximal potency was obtained with the compound having a decamethylene bridge (1e, IC50 value=1.5 μg/ml). Thus, alkylphospholipids possessing a decanmethylene bridge and a variety of substituents at position 2 (1g-n) were synthesized. They showed potent inhibitory activity with IC50 values ranging from 0.4 to 1.9 μg/ml, depending on the nature of the 2-substituent in the phospholipid molecule. In in vivo tests of the present series of alkylglycerophospholipids (1a-n), using mice bearing sarcoma 180 and mice with mammary carcinoma MM46 (both cells and compounds were given i.p.), 1-octadecyl-2-acetoacetyl-3-glyceryl ω-trimethylammoniodecyl phosphate (1e) showed the most potent life-prolonging effect. The structure-activity relationships are discussed.

  新型抗肿瘤烷基甘油磷脂是通过对血小板活化因子（PAF）分子中的磷酸胆碱部分进行修饰，从1-烷基-2-取代甘油中合成而得。通过引入具有不同长度（从2到14个碳）的亚甲基桥的极性头部磷酰基团进行了合成，并测试了其对PAF激动活性和抗肿瘤性质的影响。在一系列1-十八烷基-2-乙酰乙酰甘油磷脂（1a-f）中，随着甘油主链位置3处的磷酸和三甲铵基团之间的亚甲基桥长度增加，PAF激动活性逐渐降低，对人类早幼粒白血病细胞（HL-60）的抗肿瘤活性也发生了特征性变化。通过具有癸二烯桥的化合物（1e，IC50值=1.5μg/ml）获得了最大效力。因此，合成了具有癸二烯桥和在位置2具有各种取代基的烷基磷脂（1g-n）。它们表现出强烈的抑制活性，IC50值范围从0.4到1.9μg/ml，具体取决于磷脂分子中2-取代基的性质。在体内测试中，通过使用携带肉瘤180的小鼠和携带乳腺瘤MM46的小鼠（两种细胞和化合物均以腹腔途径给予），1-十八烷基-2-乙酰乙酰-3-甘油ω-三甲铵癸二烯磷酸酯（1e）表现出最强的延长寿命效果。讨论了结构-活性关系。
• UKAWA, KIYOSHI;IMAMIYA, EIKO;YAMAMOTO, HIROAKI;MIZUNO, KATSUTOSHI;TASAKA,+, CHEM. AND PHARM. BULL., 37,(1989) N, C. 1249-1255
  作者：UKAWA, KIYOSHI、IMAMIYA, EIKO、YAMAMOTO, HIROAKI、MIZUNO, KATSUTOSHI、TASAKA,+

  DOI：——

  日期：——