N-(cholest-5-ene-3β-oxycarbonyl alanine) | 112538-32-6

• 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
• 英文名称: N-(cholest-5-ene-3β-oxycarbonyl alanine)
• 英文别名: N-(cholest-5-en-3beta-oxycarbonyl)-beta-alanine；3-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxycarbonylamino]propanoic acid
• CAS: 112538-32-6
• 化学式: C₃₁H₅₁NO₄
• 分子量: 501.75
• InChiKey: FCHJIXBHDPREMA-MIXBDBMTSA-N

物化性质

• 熔点：
  112-114 °C
• 沸点：
  618.0±44.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(cholest-5-ene-3β-oxycarbonyl alanine) 在 甲醇 、 sodium methylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.0h， 生成 N-(N-cholesteryloxycarbonyl-3-aminopropionyl)-3-aminopropyl 1-thio-α-D-mannopyranoside
  参考文献：
  名称：

  Synthesis and evaluation of glyco-coated liposomes as drug carriers for active targeting in drug delivery systems

  摘要：

  Novel sugar-conjugated cholesterols, beta-Gal-, alpha-Man-, beta-Man-, alpha-Fuc-, and beta-Man-6P-S-beta-Ala-Chol, were synthesized and incorporated into liposomes. In vitro experiments using the glyco-coated liposomes showed that the glyco-coated liposomes are efficiently taken up by cells expressing carbohydrate-binding receptors selectively. Glyco-coated liposomes are promising candidates for drug delivery vehicles. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2014.06.028
• 作为产物：
  描述：

  methyl 3-(((((3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)carbonyl)amino)propanoate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以62%的产率得到N-(cholest-5-ene-3β-oxycarbonyl alanine)
  参考文献：
  名称：

  超声触发的瞬时凝胶-凝胶转变

  摘要：

  已经设计并合成了两种新的含有胆固醇和萘基的基于肽的异构体。我们发现，L-丙氨酸在接头中的位置可以调节胶凝特性和形态。具有L-丙氨酸残基位于连接子中间的分子（1b）显示出比直接与L-丙氨酸与萘二甲酰亚胺部分（1 a）连接的分子更好的胶凝行为。结果，在高温和高压下在乙腈中获得了具有独特核-壳结构的高度热稳定的1 b有机凝胶。此外，1a和1b的凝胶可能会因超声处理而发生瞬时的凝胶-凝胶转变。超声能打破的核-壳微球1b中和的胶束结构1到缠结纤维。通过研究这些化合物的声波触发的凝胶向凝胶转变过程的机理，可以得出结论，超声对形态有多种影响，例如切割，编织，展开，均质甚至交联。 。通常，超声可以裂解凝胶分子之间的π堆积和疏水相互作用并使之均匀化，然后重塑形态以形成新的凝胶。由声处理触发的形态转变的这种机制在材料存储和控制释放领域可能是有吸引力的。

  DOI：

  10.1002/chem.201000187

文献信息

• [EN] CELLULAR SIGNALLING INHIBITORS, THEIR FORMULATIONS AND METHODS THEREOF<br/>[FR] INHIBITEURS DE SIGNALISATION CELLULAIRE, LEURS FORMULES ET LEURS PROCÉDÉS
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2017137958A1

  公开（公告）日：2017-08-17

  The present disclosure relates generally to Cellular Signalling inhibitors of compound of Formula (I), compositions and formulations comprising the same, methods, processes, and uses thereof. In particular, the present disclosure provides CSF-1R inhibitors demonstrating sustained inhibition of CSF/CSF1R signalling pathway with decreased toxicity. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a CSF-1R inhibitor is combined with one or more of a chemotherapeutic agent, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid. The present disclosure also provides a method for treating cancer, allergy, Systemic lupus erythematosus, nephritis, Chronic Obstructive Pulmonary Disease, and abnormal macrophage functions or any combinations thereof.

  本公开涉及一般细胞信号传导抑制剂，涉及式(I)的化合物、包含该化合物的组合物和制剂、以及它们的方法、过程和使用。特别是，本公开提供了CSF-1R抑制剂，它们表现出对CSF/CSF1R信号通路的持续抑制，并且毒性降低。本公开还提供了超分子组合疗法，其中CSF-1R抑制剂与一个或多个化疗剂、激酶抑制剂和免疫调节剂结合，其中每个可选地与脂质偶联。本公开还提供了一种治疗癌症、过敏、系统性红斑狼疮、肾炎、慢性阻塞性肺病和异常巨噬细胞功能或其任何组合的方法。
• Lipids, lipid compositions, and methods of using them
  申请人：Baryza Jeremy

  公开号：US09301923B2

  公开（公告）日：2016-04-05

  Disclosed are formulation and optimization protocols for delivery of therapeutically effective amounts of biologically active agents to liver, tumors, and/or other cells or tissues. Also provided are compositions and uses for cationic lipid compounds of formula (I). The invention also relates to compositions and uses for stealth lipids of formula (XI). Also provided are processes for making such compounds, compositions, and formulations, plus methods and uses of such compounds, compositions, and formulations to deliver biologically active agents to cells and/or tissues.

  揭示了用于将生物活性剂量有效传递至肝脏、肿瘤和/或其他细胞或组织的配方和优化协议。还提供了具有式(I)的阳离子脂质化合物的组成物和用途。该发明还涉及具有式(XI)的隐身脂质的组成物和用途。此外，还提供了制备这类化合物、组成物和配方的方法，以及利用这类化合物、组成物和配方将生物活性剂传递至细胞和/或组织的方法和用途。
• Prodrug compounds, process for the preparation thereof and sustained
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04772594A1

  公开（公告）日：1988-09-20

  The invention relates to a novel prodrug compound useful in the treatment of tumors, of the formula: A--CO(CH.sub.2).sub.m (NHCO).sub.n --R wherein A is a residue of an antitumor substance having >NH or --NH.sub.2 group in the molecule, R is a residue of cholesterol, m is an integer of 1 or 2 and n is 0 or 1, and its salts.

  本发明涉及一种新型前药化合物，可用于肿瘤治疗，其化学式为：A--CO(CH.sub.2).sub.m (NHCO).sub.n --R，其中A是分子中具有>NH或--NH.sub.2基团的抗肿瘤物质的残基，R是胆固醇的残基，m为1或2的整数，n为0或1，以及其盐。
• Cholesterol anchored arabinogalactan for asialoglycoprotein receptor targeting: synthesis, characterization, and proof of concept of hepatospecific delivery
  作者：Pankaj Omprakash Pathak、Mangal Shailesh Nagarsenker、Chandrashekhar Rishikant Barhate、Sameer Govind Padhye、Vivek Vijay Dhawan、Dibyendu Bhattacharyya、C.L. Viswanathan、Frank Steiniger、Alfred Fahr

  DOI：10.1016/j.carres.2015.03.003

  日期：2015.5

  Asialoglycoprotein receptors (ASGPR) are hepatocyte bound receptors, which exhibit receptor mediated endocytosis (RME) for galactose specific moieties. Arabinogalactan (AG), a liver specific high galactose containing branched polysaccharide was hydrophobized using cholesterol (CHOL) as a lipid anchor via a two step reaction process to yield the novel polysaccharide lipid conjugated ligand (CHOL-AL-AG). CHOL-AL-AG was characterized by Fourier transform infra red (FTIR) spectroscopy, H-1 and C-13 nuclear magnetic spectroscopy (NMR), size exclusion chromatography (SEC) and differential scanning calorimetry (DSC). Conventional liposomes (CL) and surface modified liposomes (SML) containing CHOL-AL-AG were prepared using reverse phase evaporation technique. Effect of CHOL-AL-AG concentration on particle size and zeta potential of SML was evaluated. Surface morphology of CL and SML was studied using cryotransmission electron microscopy (cryo-TEM). In vitro binding affinity of SML and CL was evaluated using Ricinus communis agglutinin (RCA) assay. Cellular uptake of SML and CL was determined on ASGPR expressing HepG2 cell lines by confocal laser scanning microscopy technique (CLSM). FTIR spectra revealed bands at 1736 cm(-1) and 1664 cm(-1) corresponding to ester and carbamate functional groups, respectively. Signals at delta 0.5-2.5 corresponding to the cholestene ring and delta 3-5.5 corresponding to the carbohydrate backbone were observed in H-1 NMR spectrum of the product. CHOL-AL-AG possessed a mean average molecular weight of 27 KDa as determined by size exclusion chromatography. An endothermic peak at 207 degrees C was observed in the DSC thermogram of CHOL-AL-AG, which was not observed in thermograms of reactants and intermediate product. Synthesized CHOL-AL-AG was successfully incorporated in liposomes to yield SML. Both CL and SML possessed a mean particle size of similar to 200 nm with polydispersity index of similar to 0.25. The zeta potential of CLs was observed to be -17 mV whereas zeta potential of SMLs varied from -18 to -22 mV. RCA assay revealed enhanced binding of SML compared to CL confirming presence of galactose on surface of SML. CLSM studies demonstrated enhanced cellular uptake of SMLs compared to CL by HepG2 cells post 3 h administration indicating enhanced uptake by the ASGPR. Thus surface modified liposomes specific to target heptocytes demonstrate a promising approach for targeted drug delivery in liver cancer therapeutics. (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of glyco-coated liposomes as drug carriers for active targeting in drug delivery systems
  作者：Akiharu Ueki、Keita Un、Yuka Mino、Mitsuru Yoshida、Shigeru Kawakami、Hiromune Ando、Hideharu Ishida、Fumiyoshi Yamashita、Mitsuru Hashida、Makoto Kiso

  DOI：10.1016/j.carres.2014.06.028

  日期：2015.3

  Novel sugar-conjugated cholesterols, beta-Gal-, alpha-Man-, beta-Man-, alpha-Fuc-, and beta-Man-6P-S-beta-Ala-Chol, were synthesized and incorporated into liposomes. In vitro experiments using the glyco-coated liposomes showed that the glyco-coated liposomes are efficiently taken up by cells expressing carbohydrate-binding receptors selectively. Glyco-coated liposomes are promising candidates for drug delivery vehicles. (C) 2014 Elsevier Ltd. All rights reserved.