benzyl (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysene-3a-carboxylate | 863753-92-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: benzyl (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysene-3a-carboxylate
• 英文别名: benzyl 3β-hydroxy-21-oxolup-18-en-28-oate；benzyl (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3H-cyclopenta[a]chrysene-3a-carboxylate
• CAS: 863753-92-8
• 化学式: C₃₇H₅₂O₄
• 分子量: 560.817
• InChiKey: PODWQTKNDHWGLA-CNFIRYCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysene-3a-carboxylate 在 四(三苯基膦)钯 、 草酰氯 、 sodium carbonate 、 pyridinium chlorochromate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成 ethyl 4-((3aR,5aR,5bR,7aR,11aS,11bR,13aS)-3a-(chlorocarbonyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a-hexadecahydro-2H-cyclopenta[a]chrysen-9-yl)cyclohex-3-ene-1-carboxylate
  参考文献：
  名称：

  [EN] OXOLUPENE DERIVATIVES
  [FR] DÉRIVÉS D'OXOLUPÈNE

  摘要：

  具有药物和生物活性的化合物、其药物组合物及其用途被详细说明。特别是，提供了具有独特抗病毒活性的白桦酸衍生物，作为HIV成熟抑制剂，由公式I和II所示的化合物代表。这些化合物可用于治疗HIV和艾滋病。

  公开号：

  WO2016077561A1
• 作为产物：
  描述：

  (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-acetoxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-2,3,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-3aH-cyclopenta[a]chrysene-3a-carboxylic acid 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 benzyl (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysene-3a-carboxylate
  参考文献：
  名称：

  [EN] OXOLUPENE DERIVATIVES
  [FR] DÉRIVÉS D'OXOLUPÈNE

  摘要：

  具有药物和生物活性的化合物、其药物组合物及其用途被详细说明。特别是，提供了具有独特抗病毒活性的白桦酸衍生物，作为HIV成熟抑制剂，由公式I和II所示的化合物代表。这些化合物可用于治疗HIV和艾滋病。

  公开号：

  WO2016077561A1

文献信息

• 2-Deoxyglycoside Conjugates of Lupane Triterpenoids with High Cytotoxic Activity—Synthesis, Activity, and Pharmacokinetic Profile
  作者：Pavla Perlikova、Miroslav Kvasnica、Milan Urban、Marian Hajduch、Jan Sarek

  DOI：10.1021/acs.bioconjchem.9b00565

  日期：2019.11.20

  A set of 41 glycosidic conjugates of pentacyclic triterpenes was synthesized in order to improve the solubility of highly cytotoxic parent compounds. Their in vitro cytotoxic activity was evaluated in 25 cancer cell lines and 2 noncancer fibroblasts. Fifteen compounds had high cytotoxicity on the T-lymphoblastic leukemia cell line CCRF-CEM and 6 of them were active in multiple cell lines of various histogenic origin and not toxic in fibroblasts. Compound 11a had IC50 of 0.64 μM in CCRF-CEM cells, 0.60 μM in K-562 cells, and 0.37 μM in PC-3 cells; compound 12a had IC50 of 0.64 μM in CCRF-CEM cells and 0.71 μM in SW620 cells; compound 17b had IC50 of 0.86 μM in HCT116 cells and 0.92 μM in PC-3 cells. Compounds 11b and 12b were slightly less active than the previously mentioned derivatives; however, their solubility was significantly better, and therefore they were selected for the in vivo evaluation of the pharmacokinetic profile in mice. In both compounds, the maximum concentration in plasma was achieved very rapidly—the highest level in plasma was found 1 h after administration (22.2, respectively, 6.4 μM). For compound 12b, the resorption was followed with fast elimination, and 12 h after administration, the compound was not detected in plasma. In contrast, compound 11b was eliminated more slowly; it was still present in plasma after 12 h, but its concentration dropped below the detection limit after 24 h. The elimination half-time determined for compound 11b was 2.4 h and for compound 12b just about 1.4 h. These values are reasonable for further drug development.

  为了改善高细胞毒性母体的溶解度，我们合成了41种五环三萜糖苷复合物。在25种癌细胞系和2种非癌成纤维细胞中评估了它们的体外细胞毒性活性。15种化合物对T淋巴细胞白血病细胞系CCRF-CEM具有高细胞毒性，其中6种化合物对多种不同组织来源的细胞系具有活性，且对成纤维细胞无毒。化合物11a在CCRF-CEM细胞中的IC50为0.64μM，在K-562细胞中的IC50为0.60μM，在PC-3细胞中的IC50为0.37μM；化合物12a在CCRF-CEM细胞中的IC50为0.64μM，在SW620细胞中的IC50为0.71μM；化合物17b在HCT116细胞中的IC50为0.86μM，在PC-3细胞中的IC50为0.92μM。化合物11b和12b的活性略低于前面提到的衍生物，但溶解度明显更好，因此被选用于小鼠体内药代动力学评估。两种化合物在血浆中的最大浓度都很快达到——给药后1小时血浆中的浓度最高（分别为22
• METHOD OF PREPARATION OF A SOLUBLE FORMULATION OF WATER-INSOLUBLE PENTACYCLIC AND TETRACYCLIC TERPENOIDS, A SOLUBLE FORMULATION OF A PENTACYCLIC OR TETRACYCLIC TERPENOID AND A PHARMACEUTICAL COMPOSITION CONTAINING THIS SOLUBLE FORMULATION
  申请人：Sarek Jan

  公开号：US20090325919A1

  公开（公告）日：2009-12-31

  The invention relates to a method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpenoids, wherein the water-insoluble terpenoid having a free carboxylic, hydroxy or amino functional group is derivatized on this functional group with a substituent selected from the group comprising substituents of general formula Xa bound to the hydroxy group of the terpenoid, wherein Xa is —OC—R—COOH, substituents of general formula Xa bound to the amino group of the terpenoid, wherein Xa is —OC—R—COOH, quarternary ammonium substituents of general formula Xb bound to the carboxy group of the terpenoid, wherein Xb is —(CH2)nN+R3Y—, quarternary ammonium substituents of general formula Xc bound to the carboxy group of the terpenoid, wherein Xc je —(CH2)nR+Y—, substituents of general formula Xd bound to the carboxy group of the terpenoid, wherein Xd represents —R—COOH, glycosylic substituents Xe bound by alpha or beta glycosidic bond to the hydroxy group or to the carboxy group of the terpenoid, wherein Xe is selected from the group comprising glucosyl, galactosyl, arabinosyl, rhamnosyl, lactosyl, cellobiosyl, maltosyl and the 2-deoxyanalogues thereof, and subsequently, the prepared derivative is dissolved in the solution containing water, a cyclodextrin and optionally pharmaceutically acceptable auxiliary substances, forming an inclusion derivative with the cyclodextrin. Object of the invention is further a soluble formulation of a pentacyclic or tetracyclic triterpenoid, containing an inclusion complex of the derivatized pentacyclic or tetracyclic terpenoid with a cyclodextrin, and optionally water and pharmaceutically acceptable auxiliary substances and further a pharmaceutical composition containing the soluble formulation.

  本发明涉及一种制备水不溶性五环和四环萜类化合物可溶性配方的方法，其中具有自由羧基，羟基或氨基官能团的水不溶性萜类化合物在该官能团上被衍生物取代，所述衍生物选自包括通式Xa的取代基组成的群体，所述通式Xa与萜类化合物的羟基团结合，其中Xa为—OC—R—COOH；通式Xa与萜类化合物的氨基团结合，其中Xa为—OC—R—COOH；与萜类化合物的羧基团结合的季铵取代基通式Xb，其中Xb为—(CH2)nN+R3Y—；与萜类化合物的羧基团结合的季铵取代基通式Xc，其中Xc为—( )nR+Y—；与萜类化合物的羧基团结合的取代基通式Xd，其中Xd代表—R—COOH；通过α或β糖苷键与萜类化合物的羟基或羧基结合的糖基取代基Xe，其中Xe选自包括葡萄糖基，半乳糖基，阿拉伯糖基，鼠李糖基，乳糖基，纤维二糖基，麦芽糖基及其2-去氧衍生物的群体，随后，所制备的衍生物在含有水，环糊精和可选药学辅料的溶液中溶解，形成与环糊精的包含物衍生物。本发明的目标进一步是一种五环或四环三萜类化合物的可溶性配方，其中包含衍生的五环或四环萜类化合物与环糊精的包含物复合物，以及可选的水和药学辅料，并进一步提供了包含该可溶性配方的制药组合物。
• WO2008/37226
  申请人：——

  公开号：——

  公开（公告）日：——
• OXOLUPENE DERIVATIVES
  申请人：ViiV Healthcare UK (No.5) Limited

  公开号：US20170334946A1

  公开（公告）日：2017-11-23

  Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I and II: These compounds are useful for the treatment of HIV and AIDS.
• US8653056B2
  申请人：——

  公开号：US8653056B2

  公开（公告）日：2014-02-18