氯硫卡松丙酸酯 | 80486-69-7

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 氯硫卡松丙酸酯
• 中文别名: 氟替卡松杂质
• 英文名称: S-chloromethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate
• 英文别名: cloticasone Propionate；S-chloromethyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxo-androsta-1,4-diene-17β-carbothioate；S-Chloromethyl 6α,9-Difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate；[(6S,8S,9R,10S,11S,13S,14S,16R,17R)-17-(chloromethylsulfanylcarbonyl)-6,9-difluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate
• CAS: 80486-69-7
• 化学式: C₂₅H₃₁ClF₂O₅S
• 分子量: 517.034
• InChiKey: MVLBCBPGBUAVJQ-CENSZEJFSA-N

物化性质

• 沸点：
  583.9±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（少量溶解）、DMSO（少量溶解）、乙酸乙酯（少量溶解）、甲醇（少量溶解）

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  氯硫卡松丙酸酯 在 potassium fluoride 、 aminopolyether 2.2.2 、 potassium iodide 、 sodium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 20.0~100.0 ℃ 、140.0 kPa 条件下， 反应 3.75h， 生成 氟替卡松丙酸酯
  参考文献：
  名称：

  Automated radiosynthesis of no-carrier-added [S-fluoromethyl- 18F]fluticasone propionate as a radiotracer for lung deposition studies with PET

  摘要：

  Fluticasone propionate [(S)-fluoromethyl-6 alpha,9 alpha-difluoro-11 beta-hydroxy-16 alpha-methyl-3-oxo-17 alpha-(propionyloxy)-androsta-1,4-diene-17 beta-carbothioate; FP] is a potent anti-inflammatory steroid with several therapeutic indications, including use as an anti-asthmatic drug when administered as sized particles by inhalation from a pressurised metered-dose inhaler (pMDI). FP was successfully labelled with fluorine-18 (t(1/2) = 109.6 min; beta(+) = 100%) by displacement of tosylate with cyclotron-produced no-carrier-added [F-18]fluoride in an (S)-tosylmethyl precursor prepared from the known (S)-chloromethyl analogue of FP. Radiochemically pure [S-fluoromethyl-F-18]FP was separated by reverse phase HPLC in 35% radiochemical yield (decay-corrected) within 80 min form the end of radionuclide production (as verified by, radio-HPLC, LC-MS and LC-NMR). The radiosynthesis was automated for the safe production of high radioactivities (20-50 mCi) of [F-18]FP in a lead-shielded hot-cell for subsequent incorporation into formulated FP particles within a pMDI and subsequent study of FP deposition in human lung using positron emission tomography (PET).

  DOI：

  10.1002/(sici)1099-1344(199707)39:7<567::aid-jlcr999>3.0.co;2-p
• 作为产物：
  描述：

  6,9-二氟-11,17-二羟基-16-甲基-3-氧代雄甾-1,4-二烯-17-羧酸 在 硫化氢 、 碳酸氢钠 、 二乙胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 7.75h， 生成 氯硫卡松丙酸酯
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships in a Series of Antiinflammatory Corticosteroid Analogs, Halomethyl Androstane-17.beta.-carbothioates and -17.beta.-carboselenoates

  摘要：

  The preparation and topical antiinflammatory potencies of a series of halomethyl 17 alpha-(acyloxy)11 beta-hydroxy-3 -oxoandrosta-1,4-diene-17 beta-carbothioates, carrying combinations of 6 alpha-fluoro, 9 alpha-fluoro, 16-methyl, and 16-methylene substituents, are described. Key synthetic stages were the preparation of carbothioic acids and their reaction with dihalomethanes. The carbothioic acids were formed from 17 beta-carboxylic acids by initial reaction with dimethylthiocarbamoyl chloride followed by aminolysis of the resulting rearranged mixed anhydride with diethylamine, or by carboxyl activation with 1,1'-carbonyldiimidazole (CDI) or 2-fluoro-N-methylpyridinium tosylate (FMPT) and reaction with hydrogen sulfide, the choice of reagent being governed by the 17 alpha-substituent. Carboxyl activation with FMPT and reaction with sodium hydrogen selenide led to the halomethyl 16-methyleneandrostane-17 beta-carboselenoat analogues. Antiinflammatory potencies were measured in humans using the vasoconstriction assay and in rats and mice by a modification the Tonelli croton oil ear assay. Best activities were shown by fluoromethyl and chloromethyl carbothioates with a 17 alpha-propionyloxy group. S-Fluoromethyl 6(alpha,9 alpha-difluoro-11 beta-hydroxy-16 alpha-methyl-3-oxo-17 alpha-(propionyloxy)androsta-1,4-diene-17 beta-carbothioate (fluticasone propionate, FP) was selected for clinical study as it showed high topical antiinflammatory activity but caused little hypothalamic-pituitary-adrenal suppression after topical or oral administration to rodents.

  DOI：

  10.1021/jm00048a008

文献信息

• [EN] PEPTIDE-BASED MULTIPLE-DRUG DELIVERY VEHICLE<br/>[FR] VÉHICULE D'ADMINISTRATION DE MÉDICAMENTS MULTIPLES À BASE DE PEPTIDES
  申请人：ARIEL-UNIVERSITY RES AND DEV COMPANY LTD

  公开号：WO2017068577A1

  公开（公告）日：2017-04-27

  A molecular structure comprising a targeting moiety, a multi-functional peptide platform and a plurality of controllably released bioactive agents attached thereto is provided herein.

  本文提供了一种包括靶向基团、多功能肽平台和附着在其上的多种可控释放的生物活性剂的分子结构。
• COMBINATION THERAPY OF A HIF-2-ALPHA INHIBITOR AND AN IMMUNOTHERAPEUTIC AGENT AND USES THEREOF
  申请人：PELOTON THERAPEUTICS, INC.

  公开号：US20180140569A1

  公开（公告）日：2018-05-24

  The present invention provides methods and pharmaceutical compositions for treating proliferative disorders. The method involves step of administering to said subject a HIF-2alpha inhibitor and an immunotherapeutic agent.

  本发明提供了治疗增殖性疾病的方法和药物组合物。该方法涉及向所述受试者施用HIF-2alpha抑制剂和免疫治疗药物的步骤。
• Piperidine derivative rennin inhibitors
  申请人：——

  公开号：US20040204455A1

  公开（公告）日：2004-10-14

  Disclosed are piperidine derivatives, their manufacture and use as inhibitors of renin.

  公开了哌啶衍生物，它们的制造方法及其作为肾素抑制剂的用途。
• [EN] NOVEL GLUTAMINE ANTAGONISTS AND USES THEREOF<br/>[FR] NOUVEAUX ANTAGONISTES DE LA GLUTAMINE ET LEURS UTILISATIONS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2019071110A1

  公开（公告）日：2019-04-11

  Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder that is refractory to checkpoint inhibitor therapy, the method comprising administering to a subject in need thereof, and having the refractory disease or disorder, a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof.

  谷氨酰胺拮抗剂及其用于治疗肿瘤、免疫和神经系统疾病的方法已被披露。还披露了治疗肿瘤、免疫、传染性或神经系统疾病或紊乱的方法，该方法包括向需要治疗的受试者施用本公开的谷氨酰胺拮抗剂或其药物组成的治疗有效量。还披露了增强免疫检查点抑制剂效果的方法，使受试者对免疫检查点抑制剂产生反应，或减少免疫检查点抑制剂的毒性或剂量或治疗次数的方法，包括向需要治疗的受试者施用本公开的谷氨酰胺拮抗剂或其药物组成的治疗有效量，以及免疫检查点抑制剂。还披露了治疗对检查点抑制剂疗法无效的肿瘤、免疫、传染性或神经系统疾病或紊乱的方法，该方法包括向需要治疗的受试者施用本公开的谷氨酰胺拮抗剂或其药物组成的治疗有效量。
• [EN] THERANOSTIC CONJUGATES<br/>[FR] CONJUGUÉS THÉRANOSTIQUES
  申请人：ARIEL SCIENT INNOVATIONS LTD

  公开号：WO2021009759A1

  公开（公告）日：2021-01-21

  Provided herein is a drug delivery (DD) system for ratiometric luminescence determination of drug release degree in drug delivery monitoring, which includes a drug, a switchable reporter and non-switchable reporter providing two distinguishable signals for detection; or a single switchable reporter providing two distinguishable signals for detection, and a cleavable linker connecting a drug to a switchable reporter, as well as a method for ratiometric luminescence determination of drug release in a target in vivo or in vitro), which is effected by administering the DD system provided herein that is capable of releasing a drug from the DD system, measuring two luminescent signals provided by the switchable reporter and the non-switchable reporter, or the single switchable reporter, determining the ratio between these two luminescence signals, and determining the drug release degree through the ratio between the two luminescence signals.

  本文提供了一种药物递送（DD）系统，用于药物递送监测中药物释放程度的比例荧光测定，该系统包括一种药物、一种可切换的报告物和一种不可切换的报告物，用于提供两种可区分的信号以进行检测；或者一种单一可切换的报告物，用于提供两种可区分的信号以进行检测，以及一种可切割的连接剂，连接药物和可切换的报告物，以及一种比例荧光测定方法，用于在目标（体内或体外）中测定药物释放，通过给予本文提供的能够从DD系统中释放药物的DD系统，测量可切换的报告物和不可切换的报告物提供的两个发光信号，或者单一可切换的报告物，确定这两个发光信号之间的比例，并通过这两个发光信号之间的比例确定药物释放程度。