摩熵化学
数据库官网
小程序
打开微信扫一扫
首页 分子通 化学资讯 化学百科 反应查询 关于我们
请输入关键词

西罗莫司脂化物 | 162635-04-3

中文名称
西罗莫司脂化物
中文别名
西罗莫司;替西罗莫司;雷帕霉素42-[3-羟基-2-(羟甲基)-2-甲基丙酸酯
英文名称
temsirolimus
英文别名
(1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontyne-3-yl]propyl}-2-methoxycyclohexyl-3-hydroxy-2-(hydroxylmethyl)-2-methylpropanoate;(1R,2R,4S)-4-[(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl]-2-methoxycyclohexyl-3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate;(1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate;rapamycin 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate];42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]rapamycin;[(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] 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate
西罗莫司脂化物化学式
CAS
162635-04-3
化学式
C56H87NO16
mdl
——
分子量
1030.3
InChiKey
CBPNZQVSJQDFBE-FUXHJELOSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    99-101°C
  • 沸点:
    1048.4±75.0 °C(Predicted)
  • 密度:
    1.21
  • 闪点:
    587.8℃
  • 溶解度:
    易溶于可溶于氯仿、甲醇。
  • 物理描述:
    Solid
  • 颜色/状态:
    White to off-white powder
  • 解离常数:
    No ionizable functional groups

计算性质

  • 辛醇/水分配系数(LogP):
    5.6
  • 重原子数:
    73
  • 可旋转键数:
    11
  • 环数:
    4.0
  • sp3杂化的碳原子比例:
    0.75
  • 拓扑面积:
    242
  • 氢给体数:
    4
  • 氢受体数:
    16

ADMET

代谢
西罗莫司是坦西莫司的活性代谢物,是人类静脉给药后主要的代谢物。其余代谢物在血浆中的放射性不到10%。
Sirolimus, an active metabolite of temsirolimus, is the principal metabolite in humans following intravenous treatment. The remainder of the metabolites account for less than 10% of radioactivity in the plasma.
来源:Hazardous Substances Data Bank (HSDB)
代谢
Temsirolimus 通过解代谢为西罗莫司,后者是主要的活性代谢物。Temsirolimus 和西罗莫司均通过细胞色素 P-450(CYP)同工酶 3A4 进行代谢。尽管 Temsirolimus 被代谢为西罗莫司,但 Temsirolimus 本身具有抗肿瘤活性,并不被认为是一种前药。
Temsirolimus is metabolized by hydrolysis to sirolimus, the principal active metabolite. Both temsirolimus and sirolimus also are metabolized by cytochrome P-450 (CYP) isoenzyme 3A4. Although temsirolimus is metabolized to sirolimus, temsirolimus itself exhibits antitumor activity and is not considered a prodrug.
来源:Hazardous Substances Data Bank (HSDB)
代谢
体外代谢的研究使用了人肝微体和重组人细胞色素P450酶,包括CYP3A4、1A2、2A6、2C8、2C9、2C19和2E1。通过液相色谱-串联质谱(LC-MS/MS或MS/MS/MS)检测到了15个代谢物。CYP3A4被鉴定为主要负责该化合物代谢的酶。与重组CYP3A4的孵育产生了大多数通过人肝微体孵育检测到的代谢物,这用于大规模制备代谢物。通过硅胶色谱和半制备反相色谱,分离和纯化了各个代谢物,以进行结构鉴定和生物活性研究。通过正负质谱(MS)和MS/MS光谱方法,将小量代谢物(峰1-7)鉴定为羟基化或去甲基化的巨环内酯环开环的替西罗利姆衍生物。由于这些化合物不稳定且仅以微量存在,因此没有进行进一步的研究。通过结合LC-MS、MS/MS、MS/MS/MS和NMR技术,确定了六个主要代谢物,分别为36-羟基替西罗利姆(M8)、35-羟基替西罗利姆(M9)、开环的11-羟基替西罗利姆(M10和M11)、N-氧化替西罗利姆(M12)和32-O-去甲基替西罗利姆(M13)。与母体化合物相比,这些代谢物对LNCaP细胞增殖的活性显著降低。
The in vitro metabolism of temsirolimus, (rapamycin-42-[2,2-bis-(hydroxymethyl)]-propionate), an antineoplastic agent, was studied using human liver microsomes as well as recombinant human cytochrome P450s, namely CYP3A4, 1A2, 2A6, 2C8, 2C9, 2C19, and 2E1. Fifteen metabolites were detected by liquid chromatography (LC)-tandem mass spectrometry (MS/MS or MS/MS/MS). CYP3A4 was identified as the main enzyme responsible for the metabolism of the compound. Incubation of temsirolimus with recombinant CYP3A4 produced most of the metabolites detected from incubation with human liver microsomes, which was used for large-scale preparation of the metabolites. By silica gel chromatography followed by semipreparative reverse-phase high-performance liquid chromatography, individual metabolites were separated and purified for structural elucidation and bioactivity studies. The minor metabolites (peaks 1-7) were identified as hydroxylated or desmethylated macrolide ring-opened temsirolimus derivatives by both positive and negative mass spectrometry (MS) and MS/MS spectroscopic methods. Because these compounds were unstable and only present in trace amounts, no further investigations were conducted. Six major metabolites were identified as 36-hydroxyl temsirolimus (M8), 35-hydroxyl temsirolimus (M9), 11-hydroxyl temsirolimus with an opened hemiketal ring (M10 and M11), N- oxide temsirolimus (M12), and 32-O-desmethyl temsirolimus (M13) using combined LC-MS, MS/MS, MS/MS/MS, and NMR techniques. Compared with the parent compound, these metabolites showed dramatically decreased activity against LNCaP cellular proliferation.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 肝毒性
血清转酶升高发生在30%到40%接受坦西罗利姆治疗的病人中,碱性磷酸酶升高发生在60%到70%的病人中,但这些异常通常是轻微的、无症状的,并且是自限性的,很少需要调整剂量或停药。肝酶升高超过正常上限5倍的情况只发生在1%到3%的病人中。自从批准并广泛临床使用以来,没有报告因使用坦西罗利姆而导致的明显临床肝损伤的案例。坦西罗利姆和西罗利姆一样,具有免疫抑制作用,乙肝病毒再激活被认为是治疗的可能并发症。然而,尽管有超过10年的临床使用,没有报告因坦西罗利姆治疗而导致的乙肝病毒再激活。因此,由于坦西罗利姆导致的急性肝损伤和黄疸可能是非常罕见的,如果真的发生的话。对坦西罗利姆输注的过敏反应并不少见(因此推荐使用抗组胺药进行预处理),并且已经报告了史蒂文斯-约翰逊综合征的病例。
Serum aminotransferase elevations occur in 30% to 40% and alkaline phosphatase in 60% to 70% of patients receiving temsirolimus, but the abnormalities are usually mild, asymptomatic and self-limiting, rarely requiring dose modification or discontinuation. Elevations of liver enzymes above 5 times the upper limit of normal occur in only 1% to 3% of patients. Since approval and wide spread clinical use, there have been no case reports of clinically apparent liver injury attributed to temsirolimus use. Temsirolimus, like sirolimus, is immunosuppressive, and reactivation of hepatitis B is considered a possible complication of therapy. Yet despite more than 10 years of clinical use, there have been no reports of reactivation of hepatitis B attributed to temsirolimus therapy. Thus, acute liver injury with jaundice due to temsirolimus is probably quite rare, if it occurs at all. Hypersensitivity reactions to temsirolimus infusions are not uncommon (for which reason premedication with an antihistamine is recommended) and instances of Stevens Johnson syndrome have been reported.
来源:LiverTox
毒理性
  • 在妊娠和哺乳期间的影响
使用期间总结:坦西罗利姆是西罗利姆的前药。由于缺乏关于坦西罗利姆或西罗利姆在哺乳期间使用的信息,建议使用其他药物,特别是在哺乳新生儿或早产儿时。制造商建议在坦西罗利姆治疗期间及最后剂量后的3周内停止哺乳。 对哺乳婴儿的影响:截至修订日期,未找到相关的已发布信息。 对泌乳和母乳的影响:截至修订日期,未找到相关的已发布信息。
◉ Summary of Use during Lactation:Temsirolimus is a prodrug of sirolimus. Because no information is available on the use of temsirolimus or sirolimus during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The manufacturer recommends that breastfeeding be discontinued during temsirolimus therapy and for 3 weeks following the last dose. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)
毒理性
  • 相互作用
CYP3A4抑制剂:潜在的药代动力学相互作用(主要活性代谢物西罗莫司的血药浓度增加)。应避免与强效CYP3A4抑制剂同时使用;如果没有替代品,应考虑调整替西罗莫司的剂量。
CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma concentrations of the principal active metabolite sirolimus). Concomitant use with a potent CYP3A4 inhibitors should be avoided; if no alternative is available, consideration should be given to temsirolimus dosage adjustment.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
CYP3A4诱导剂:潜在的药代动力学相互作用(主要活性代谢物西罗莫司的血浆浓度降低)。应避免与强效CYP3A4诱导剂同时使用;如果没有替代品,应考虑调整坦西莫司的剂量。
CYP3A4 inducers: Potential pharmacokinetic interaction (decreased plasma concentrations of the principal active metabolite sirolimus). Concomitant use with potent CYP3A4 inducers should be avoided; if no alternative is available, consideration should be given to temsirolimus dosage adjustment.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
血管性肿型反应在同时使用血管紧张素转换酶(ACE)抑制剂治疗期间观察到。建议谨慎。
Angioedema-type reactions observed during concomitant therapy with angiotensin-converting enzyme (ACE) inhibitors. Caution is advised.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在癌症患者中单次给予25毫克剂量的坦西莫利布斯后,全血中坦西莫利布斯的平均Cmax为585 ng/mL(变异系数,CV=14%),血液中的平均AUC为1627 ng·hr/mL(CV=26%)。通常Cmax发生在输注结束时。在1毫克到25毫克的剂量范围内,坦西莫利布斯的暴露量增加幅度小于剂量比例,而西罗利布斯的暴露量则与剂量成比例增加。在癌症患者中单次给予25毫克静脉剂量后,西罗利布斯的AUC是坦西莫利布斯AUC的2.7倍,这主要是由于西罗利布斯半衰期较长。
Following administration of a single 25 mg dose of temsirolimus in patients with cancer, mean temsirolimus Cmax in whole blood was 585 ng/mL (coefficient of variation, CV =14%), and mean AUC in blood was 1627 ng.hr/mL (CV=26%). Typically Cmax occurred at the end of infusion. Over the dose range of 1 mg to 25 mg, temsirolimus exposure increased in a less than dose proportional manner while sirolimus exposure increased proportionally with dose. Following a single 25 mg intravenous dose in patients with cancer, sirolimus AUC was 2.7-fold that of temsirolimus AUC, due principally to the longer half-life of sirolimus.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在给予单次25毫克静脉注射后,患有癌症的患者全血中替西罗利姆的稳态分布体积为172升。替西罗利姆和西罗利姆都会广泛地分配到形成的血细胞中。
Following a single 25 mg intravenous dose, mean steady-state volume of distribution of temsirolimus in whole blood of patients with cancer was 172 liters. Both temsirolimus and sirolimus are extensively partitioned into formed blood elements.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在癌症患者中,单次给予25毫克坦西罗利姆后,坦西罗利姆的平均(变异系数)系统清除率为16.2(22%)升/小时。
Following a single 25 mg dose of temsirolimus in patients with cancer, temsirolimus mean (CV) systemic clearance was 16.2 (22%) L/hr.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
未知他克莫司是否会被分泌入人乳中...
It is not known whether temsirolimus is excreted into human milk...
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
静脉注射单次放射性标记的替西罗莫司剂量后,大约78%的总放射性在14天内通过粪便回收,4.6%通过尿液回收。
Following IV administration of a single radiolabeled dose of temsirolimus, approximately 78% of the total radioactivity is recovered in feces and 4.6% in urine within 14 days.
来源:Hazardous Substances Data Bank (HSDB)

安全信息

  • 安全说明:
    S24/25
  • WGK Germany:
    3
  • 海关编码:
    29349990

SDS

SDS:c9c899c15680a290b667b3791bf8b503
查看

制备方法与用途

概述

替西罗莫司(temsirolimus),又称西罗莫司酯化物,是由辉瑞医药研发的一种靶向性抗肿瘤药物,用于治疗进展性肾癌。它是首个针对肾癌的靶向治疗药物,并且是唯一上市的特异性抑制mTOR激酶的药物。

相关研究

mTOR激酶在调节细胞增殖、生长和存活方面起着重要作用。体外研究表明,替西罗莫司通过抑制mTOR激酶导致血管内皮生长因子(VEGF)平下降,进而阻止新生血管的发展,最终导致癌细胞死亡

应用

在我国尚未上市,但国外的临床试验结果显示,替西罗莫司对晚期肾癌有较好的疗效,具有广阔的应用前景。

药理作用

mTOR是一种多功能激酶,属于磷脂酰肌醇3激酶(PI3K)蛋白激酶家族成员。作为PI3K/AKT信号通路的下游效应蛋白,其底物主要控制与细胞生长和增殖密切相关的蛋白质合成。肾透明细胞癌中普遍存在PI3K-AKT-mTOR信号传导通路的过度激活。

制备
  1. 坦罗莫司半成品制备:将8.3g粗品(纯度75.68%,西罗莫司3.47%,异构体16.48%)溶解于25mL乙酸乙酯中,上样至正相球填料柱进行梯度洗脱。在20℃条件下收集组分,并在30℃下减压浓缩至干,得到纯度为84.78%,西罗莫司0.02%,异构体13.28%的半成品。

  2. 进一步精制:通过后续处理,最终获得高纯度的替西罗莫司产品。

体内与体外研究
  • 体外研究替西罗莫司抑制核糖体蛋白S6磷酸化。在PTEN阳性的DU145细胞中比在PTEN阴性的PC-3细胞中更为有效,且能够显著抑制细胞生长和克隆存活,作用呈浓度依赖性。对原代人淋巴细胞性白血病(ALL)细胞的处理也显示了显著抑制增殖并诱导凋亡的效果。

  • 体内研究替西罗莫司以20 mg/kg剂量腹腔注射,每周5天,能够显著延迟DAOY移植瘤生长。在较高剂量(100 mg/kg)下单独给药一周内,肿瘤体积下降37%。处理两周也延缓了对Rapamycin耐受的U251移植瘤生长。此外,在患Huntington疾病的小鼠模型中,替西罗莫司能够抑制mTOR并改善多种行为任务表现。它还能够在皮下诱导显著的抗癌反应,并在携带人ALL的NOD/SCID移植瘤模型中降低外周血膨胀和脾肿大。

这些研究结果表明替西罗莫司具有良好的治疗潜力,特别是在抗肿瘤方面显示出显著效果。

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

点击查看最新优质反应信息

文献信息

  • [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
    申请人:GILEAD APOLLO LLC
    公开号:WO2017075056A1
    公开(公告)日:2017-05-04
    The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
    本发明提供了化合物I和II,这些化合物可用作乙酰辅酶A羧化酶(ACC)的抑制剂,以及它们的组合物和使用方法。
  • [EN] METALLOENZYME INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE MÉTALLOENZYMES
    申请人:VPS 3 INC
    公开号:WO2018165520A1
    公开(公告)日:2018-09-13
    Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.
    提供具有HDAC6调节活性的化合物,以及通过HDAC6介导的治疗疾病、疾病或症状的方法。
  • IRAK DEGRADERS AND USES THEREOF
    申请人:Kymera Therapeutics, Inc.
    公开号:US20190192668A1
    公开(公告)日:2019-06-27
    The present invention provides compounds, compositions thereof, and methods of using the same.
    本发明提供了化合物、其组合物以及使用这些化合物的方法。
  • CYCLIC ETHER PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
    申请人:Genentech, Inc.
    公开号:US20140088117A1
    公开(公告)日:2014-03-27
    Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein R 2 is a cyclic ether and X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
    公式I的环醚吡唑-4-基-杂环基-羧酰胺化合物,包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐,其中R2为环醚,X为噻唑基、吡啶基、吡啶基或嘧啶基,可用于抑制Pim激酶,并用于治疗由Pim激酶介导的癌症等疾病。公开了使用公式I化合物进行体外、体内和体内诊断、预防或治疗哺乳动物细胞中的这类疾病或相关病理条件的方法。
  • [EN] COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF SHP2<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR INHIBER L'ACTIVITÉ DE SHP2
    申请人:NOVARTIS AG
    公开号:WO2016203404A1
    公开(公告)日:2016-12-22
    The present invention relates to compounds of formula I. The compounds are inhibitors of the Src Homolgy-2 phosphatase (SHP2) and thus useful in the treatment of Noonan Syndrome, Leopard Syndrome and cancer.
    本发明涉及式I的化合物。这些化合物是Src同源-2磷酸酶(SHP2)的抑制剂,因此在努南综合征、豹纹综合征和癌症的治疗中有用。
查看更多

同类化合物

马杜霉素II 雷帕霉素 长川霉素 达福普丁甲磺酸 西罗莫司脂化物 西罗莫司异构体C 蛎灰菌素A 柠檬提取物 子囊霉素 威里霉素 唑他莫司 吡美莫司 双氢他克莫司 去甲氧基雷帕霉素 去甲基他克莫司 化合物 T32504 化合物 T25424 依维莫司EP杂质E 依维莫司 他克莫司杂质5 他克莫司开环杂质 他克莫司31-DMT 他克莫司 乌米里莫斯 FK-506一水合物 8-表他克莫司 8,9,14,15,24,25,26,26alpha-八氢-14-羟基-4,12-二甲基-3-(1-甲基乙基)-(3R,4R,5E,10E,12E,14S,26alphaR)-3H-21,18-次氮基-1H,22H-吡咯并[2,1-c][1,8,4,19]二氧杂二氮杂二十四环-1,7,16,22(4H,17H)-四酮 7-去甲氧基-7-乙氧基-42-O-(2-羟基乙基)雷帕霉素 42-O-[2-[[羟基[2-(三甲基铵)乙氧基]亚膦酰基]氧基]乙基]雷帕霉素内盐 42-(二甲基亚膦酰)雷帕霉素 42-(2-四唑基)雷帕霉素 40-O-[2-(叔丁基二甲硅基)氧代]乙基雷帕霉素 37-去亚甲基24,33-二-O-(叔-丁基二甲基硅烷基)-37-氧代-FK-506 31-O-去甲基-Fk506 28-O-甲基-雷帕霉素 24,33-二-O-(叔-丁基二甲基硅烷基)-37,38-去氢-37,38-二羟基-FK-506 24,32-双-O-(tert-butyldimethylsilyl)-他克莫司 22-羟基-33-叔-丁基二甲基硅烷基氧基-异-FK-506 2-甲氧基-5-硝基嘧啶-4-胺 2-异丙基-2-甲基噁丙环 2,6-二(1-甲基丙基)-p-甲苯酚 19-表FK-506 15-O-去甲基长川霉素 13-O-去甲基子囊霉素 13,15-O-二去甲基长川霉素 (E/Z)-FK-50626,28-烯丙酸酯 (9Z)-8-乙基-5,15,19-三羟基-3-[(E)-2-(4-羟基-3-甲氧基环己基)-1-甲基乙烯基]-14-甲氧基-4,10,12,18-四甲基-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-十六氢-3H-16,19-环氧吡啶并[2,1-c][1,4]噁吖环二十三英-1,7,20,21(4H,23H)-t (4R,7R,8R,9Z,14E,16E,18S)-18-羟基-7-异丙基-4,8,16-三甲基-6,23-二氧杂-3,12,25-三氮杂双环[20.2.1]二十五-1(24),9,14,16,22(25)-五烯-2,5,11,20-四酮 (2S,5S,6R,10R,11S)-10-庚基-6-羟基-4,11-二甲基-5-(苯基甲基)-2-丙-2-基-1,9-二氧杂-4-氮杂环十二烷-3,8,12-三酮 (1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯