40-(R)-trifluoromethanesulfonylrapamycin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: 40-(R)-trifluoromethanesulfonylrapamycin
• 英文别名: [(1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl] trifluoromethanesulfonate
• 化学式: C₅₂H₇₈F₃NO₁₅S
• 分子量: 1046.25
• InChiKey: BBAKURMOLWTFDW-HGUXUYOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  72
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  227
• 氢给体数：
  2
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  40-(R)-trifluoromethanesulfonylrapamycin 在 copper(ll) sulfate pentahydrate 、 叠氮化四丁基铵 、 sodium ascorbate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成
  参考文献：
  名称：

  Synthesis of rapamycin glycoconjugates via a CuAAC-based approach

  摘要：

  The conversion of the C40 secondary hydroxyl group of rapamycin into the azido group was followed by copper catalyzed cycloaddition of the resulting azido-rapamcin with various unprotected propargyl O-and S-glycosides and a C-ethynyl derivative. This approach furnished a collection of triazole-bridged rapamycin glycoconjugates (14 examples) in 44-83% isolated yield. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.10.026
• 作为产物：
  描述：

  三氟甲磺酸酐 、 雷帕霉素 在 2,6-二甲基吡啶 作用下， 以 醋酸异丙酯 为溶剂， 反应 0.67h， 生成 40-(R)-trifluoromethanesulfonylrapamycin
  参考文献：
  名称：

  One pot synthesis of tetrazole derivatives of sirolimus

  摘要：

  提供了一种单步、一锅法的方法来大规模获得左旋西罗莫司和其他雷帕霉素衍生物，该方法改进了目前可用的合成方案。在一种实施例中，干燥的雷帕霉素溶解在丙酮酸异丙酯（IPAc）中。溶液冷却后，加入2,6-二甲基吡啶，随后缓慢加入三氟甲磺酸酐，在-30°C下进行。通过过滤去除盐。向三氟甲磺酸酯溶液中加入四唑，随后加入一种叔基二异丙基乙基胺（DIEA）的叔碱。在室温下孵育后，产品被浓缩并通过硅胶柱使用THF/庚烷作为洗脱剂进行纯化。收集含有产品的分数，浓缩并再次使用丙酮/庚烷柱进行纯化。含有产品的分数被浓缩。将产品溶解在t-BME中，用庚烷沉淀。将固体溶解在丙酮中，加入叔丁基羟基甲苯（BHT），并浓缩溶液。使用丙酮重复两次此过程以去除溶剂。在干燥之前添加至少一种稳定剂，例如0.5%的BHT。

  公开号：

  US20080167335A1

文献信息

• RAFAMYCIN ANALOGS AND METHODS FOR MAKING SAME
  申请人：HANGZHOU ZYLOX PHARMA CO., LTD

  公开号：US20150051242A1

  公开（公告）日：2015-02-19

  A semi-synthetic rapamycin analog with a triazole moiety or a pharmaceutically acceptable salt or prodrug thereof, is a broad-spectrum cytostatic agent and a mTOR inhibitor, and is useful in the treatment of various cancers, or tumors in organs such as kidney, liver, breast, head and neck, lung, prostate, and restenosis in coronary arteries, peripheral arteries, and arteries in the brain, immune and autoimmune diseases. Also disclosed are fungal growth-, restenosis-, post-transplant tissue rejection- and immune- and autoimmune disease-inhibiting compositions and a method of inhibiting cancer, fungal growth, restenosois, post-transplant tissue rejection, and immune and autoimmune disease in a mammal. One particular preferred application of such triazole-moiety containing rapamycin analog is in treating renal carcinoma, lung cancer, colon cancer, and breast cancers wherein potency of the drug, its half-life, tissue distribution properties, and its pharmacokinetic properties including bioavailability through oral and intravenous routes are essential to the clinical outcomes.

  一种含有三唑基团或其药用可接受盐或前药的半合成雷帕霉素类似物，是一种广谱细胞静止剂和 mTOR 抑制剂，可用于治疗各种癌症或器官肿瘤，如肾脏、肝脏、乳腺、头颈部、肺部、前列腺，以及冠状动脉、外周动脉和脑动脉的再狭窄，免疫和自身免疫疾病。还公开了抑制真菌生长、再狭窄、移植后组织排斥以及免疫和自身免疫疾病的组合物和在哺乳动物中抑制癌症、真菌生长、再狭窄、移植后组织排斥以及免疫和自身免疫疾病的方法。其中一种特定的首选应用是含有三唑基团的雷帕霉素类似物在治疗肾癌、肺癌、结肠癌和乳腺癌方面，药物的效力、半衰期、组织分布特性以及其药代动力学特性，包括口服和静脉途径的生物利用度对临床结果至关重要。
• One pot synthesis of tetrazole derivatives of sirolimus
  申请人：Dhaon Madhup K.

  公开号：US20080167335A1

  公开（公告）日：2008-07-10

  A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale is presented, which improves currently available synthesis schemes. In one embodiment, dried rapamycin is dissolved in isopropylacetate (IPAc). The solution is cooled, and 2,6-Lutidine is added, followed slowly adding triflic anhydride at −30° C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine (DIEA) is added to the triflate solution. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated. The process is repeated twice with acetone to remove solvents. At least one stabilizing agent is added, such as BHT at 0.5% before drying.

  提供了一种单步、一锅法的方法来大规模获得左旋西罗莫司和其他雷帕霉素衍生物，该方法改进了目前可用的合成方案。在一种实施例中，干燥的雷帕霉素溶解在丙酮酸异丙酯（IPAc）中。溶液冷却后，加入2,6-二甲基吡啶，随后缓慢加入三氟甲磺酸酐，在-30°C下进行。通过过滤去除盐。向三氟甲磺酸酯溶液中加入四唑，随后加入一种叔基二异丙基乙基胺（DIEA）的叔碱。在室温下孵育后，产品被浓缩并通过硅胶柱使用THF/庚烷作为洗脱剂进行纯化。收集含有产品的分数，浓缩并再次使用丙酮/庚烷柱进行纯化。含有产品的分数被浓缩。将产品溶解在t-BME中，用庚烷沉淀。将固体溶解在丙酮中，加入叔丁基羟基甲苯（BHT），并浓缩溶液。使用丙酮重复两次此过程以去除溶剂。在干燥之前添加至少一种稳定剂，例如0.5%的BHT。
• MEDICAL DEVICES CONTAINING RAPAMYCIN ANALOGS
  申请人：Abbott Laboratories

  公开号：US20160220739A1

  公开（公告）日：2016-08-04

  A medical device comprises a supporting structure capable of containing or supporting a pharmaceutically acceptable carrier or excipient, which carrier or excipient may contain one or more therapeutic agents or substances, with the carrier preferably including a coating on the surface thereof, and the coating containing the therapeutic substances, such as, for example, drugs. Supporting structures for the medical devices that are suitable for use in this invention include, but are not limited to, coronary stents, peripheral stents, catheters, arterio-venous grafts, by-pass grafts, and drug delivery balloons used in the vasculature. Drugs that are suitable for use in this invention include, but are not limited to drugs of Formula (I). The drugs of Formula (I) can be used in combination with another drug including those selected from anti-proliferative agents, anti-platelet agents, anti-inflammatory agents, anti-thrombotic agents, cytotoxic drugs, agents that inhibit cytokine or chemokine binding, cell de-differentiation inhibitors, anti-lipaedemic agents, matrix metalloproteinase inhibitors, cytostatic drugs, or combinations of these drugs.

  一种医疗器械包括一个支撑结构，该支撑结构能够容纳或支撑一种药学上可接受的载体或赋形剂，该载体或赋形剂可以含有一个或多个治疗剂或物质，其中载体最好在其表面包含一层涂层，该涂层含有治疗物质，例如药物。适用于本发明的医疗器械的支撑结构包括但不限于冠状动脉支架、外周支架、导管、动静脉移植物、旁路移植物和用于血管系统的药物输送球。适用于本发明的药物包括但不限于公式（I）中的药物。公式（I）中的药物可以与另一种药物结合使用，包括从抗增殖剂、抗血小板剂、抗炎剂、抗血栓剂、细胞毒性药物、抑制细胞因子或趋化因子结合的药物、细胞去分化抑制剂、降脂药、基质金属蛋白酶抑制剂、细胞周期停滞药或这些药物的组合中选择的药物。
• [EN] RAPAMYCIN ANALOGS AND METHODS FOR MAKING SAME<br/>[FR] ANALOGUE DE LA RAPAMYCINE ET PROCÉDÉS DE FABRICATION ASSOCIÉS
  申请人：HANGZHOU ZYLOX PHARMA CO LTD

  公开号：WO2014082286A9

  公开（公告）日：2014-11-13
• [EN] PROTEIN-BINDING COMPOUNDS<br/>[FR] COMPOSÉS À LIAISON PROTÉINIQUE
  申请人：BAYLE JOSEPH HENRI

  公开号：WO2020076738A3

  公开（公告）日：2020-05-22