L-serine myristylamide | 171191-20-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: L-serine myristylamide
• 英文别名: (2S)-2-amino-3-hydroxy-N-tetradecylpropanamide；(S)-2-amino-3-hydroxy-N-tetradecylpropanamide
• CAS: 171191-20-1
• 化学式: C₁₇H₃₆N₂O₂
• 分子量: 300.485
• InChiKey: JMBPGLKXSPHDNV-INIZCTEOSA-N

物化性质

• 沸点：
  490.2±35.0 °C(Predicted)
• 密度：
  0.948±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-serine myristylamide 、 三甲基乙酸 在 1-羟基苯并三唑 、 N-甲基吗啉 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以72.9%的产率得到(S)-3-hydroxy-2-pivalamido-N-tetradecylpropanamide
  参考文献：
  名称：

  [EN] COMPOUNDS, THEIR SYNTHESES, COMPOSITIONS, AND METHODS TO TREAT CANCER
  [FR] COMPOSÉS, LEURS SYNTHÈSES, LEURS COMPOSITIONS ET MÉTHODES POUR TRAITER LE CANCER

  摘要：

  公开号：

  WO2010093615A3
• 作为产物：
  描述：

  十四胺 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 L-serine myristylamide
  参考文献：
  名称：

  Synthesis of Sulfated Cerebroside Analogs Having Mimicks of Ceramide and Their Anti-human Immunodeficiency Virus Type 1 Activities.

  摘要：

  以过-O-乙酰化 D-葡萄糖、过-O-乙酰化 D-半乳糖和过-O-乙酰化 D-乳糖为神经酰胺分子，以乙二醇十二烷基醚、3-二十二烷氧基-1-丙醇、2-羟甲基-1，3-O-二肉豆蔻基-1，3-丙二醇和 L-丝氨酸二酰胺衍生物为神经酰胺分子，制备了各种硫酸化脑苷脂类似物，它们是脑苷脂的模拟物。合成的硫酸化糖脂具有抗 HIV-1 活性。

  DOI：

  10.1248/cpb.43.594

文献信息

• [EN] SPHINGO-GUANIDINES AND THEIR USE AS INHIBITORS OF SPHINGOSINE KINASE<br/>[FR] SPHINGO-GUANIDINES ET LEUR EMPLOI EN TANT QU'INHIBITEURS DE SPHINGOSINE KINASE
  申请人：MUSC FOUND FOR RES DEV

  公开号：WO2010078247A1

  公开（公告）日：2010-07-08

  The presently disclosed subject matter provides compounds of the formula:(1) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, and R8 are as defined herein. Also disclosed are methods for making the compounds of the formula as set forth hereinabove, their use in inhibiting sphingosine kinase, and their use in the treatment and/or prevention of diseases and/or conditions associated with undesirable ceramidase or sphingosine kinase activity, including, but not limited to, cancer, cancer metastasis, atherosclerosis, stenosis, inflammation, immunological disorders, asthma, atopic dermatitis, wound healing, and other proliferative diseases.

  目前公开的主题提供了以下式子(1)的化合物及其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7和R8如本文所定义。还公开了制备上述式子的化合物的方法，它们用于抑制鞘氨醇激酶，以及它们用于治疗和/或预防与不良鞘氨醇酶或鞘氨醇激酶活性相关的疾病和/或病况，包括但不限于癌症、癌症转移、动脉硬化、狭窄、炎症、免疫性疾病、哮喘、特应性皮炎、伤口愈合和其他增生性疾病。
• COMPOUNDS, THEIR SYNTHESES, COMPOSITIONS, AND METHODS TO TREAT CANCER
  申请人：Beckman Barbara S.

  公开号：US20120027844A1

  公开（公告）日：2012-02-02

  Compounds and their syntheses are disclosed herein. Compositions and pharmaceutical compositions comprising a compound are also described, and include compositions also comprising liposomes. Methods for the treatment of cancer in animals comprising administering a compound or a composition comprising a compound are also described.

  本文披露了化合物及其合成方法。还描述了包含化合物的组合物和药物组合物，其中包括还包含脂质体的组合物。还描述了用于治疗动物癌症的方法，包括给动物施用化合物或包含化合物的组合物。
• Design, Synthesis, and Biological Activity of a Family of Novel Ceramide Analogues in Chemoresistant Breast Cancer Cells
  作者：James W. Antoon、Jiawang Liu、Matthew M. Gestaut、Matthew E. Burow、Barbara S. Beckman、Maryam Foroozesh

  DOI：10.1021/jm9009668

  日期：2009.9.24

  Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic intervention using these ceramide analogues inhibited clonogenic survival and induced apoptosis, with one analogue being more effective than C8-ceramide. Our results show ceramide-based therapy has therapeutic potential in treating drug resistant breast cancer.
• 3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells
  作者：Adharsh P. Ponnapakam、Jiawang Liu、Kaustubh N. Bhinge、Barbara A. Drew、Tony L. Wang、James W. Antoon、Thong T. Nguyen、Patrick S. Dupart、Yuji Wang、Ming Zhao、Yong-Yu Liu、Maryam Foroozesh、Barbara S. Beckman

  DOI：10.1016/j.bmc.2013.12.065

  日期：2014.2

  Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive as corresponding regular cancer cells under the exposure to anticancer ceramide analogs. In this work we designed five new ceramide analogs with different backbones, in order to test the hypothesis that extending the conjugated system in ceramide analogs would lead to an increase of their anticancer activity and selectivity towards resistant cancer cells. The analogs with the 3-ketone-4,6-diene backbone show the highest apoptosis-inducing efficacy. The most potent compound, analog 406, possesses higher pro-apoptotic activity in chemo-resistant cell lines MCF-7TN-R and NCI/ADR-RES than the corresponding chemo-sensitive cell lines MCF-7 and OVCAR-8, respectively. However, this compound shows the same potency in inhibiting the growth of another pair of chemo-sensitive and chemo-resistant cancer cells, MCF-7 and MCF-7/Dox. Mechanism investigations indicate that analog 406 can induce apoptosis in chemo-resistant cancer cells through the mitochondrial pathway. Cellular glucosylceramide synthase assay shows that analog 406 does not interrupt glucosylceramide synthase in chemo-resistant cancer cell NCI/ADR-RES. These findings suggest that due to certain intrinsic properties, ceramide analogs' pro-apoptotic activity is not disrupted by the normal drug-resistance mechanisms, leading to their potential use for overcoming cancer multidrug-resistance. (C) 2014 Elsevier Ltd. All rights reserved.
• Inhibition of breast tumor growth in mice after treatment with ceramide analog 315
  作者：Tulasi Ponnapakkam、Tyjah Saulsberry、Tarius Hill、Miriam Hill-Odom、Navneet Goyal、Murali Anbalagan、Jiawang Liu、Maryam Foroozesh

  DOI：10.1097/cad.0000000000000675

  日期：2018.10

  The aim of this study was to evaluate the anticancer and antitumor activities of ceramide analog 315 in nude mice. Nude mice (n = 10) were injected bilaterally with 5 x 10(6) MDA-MB-231 cells on each side. Tumors were allowed to form for 2 weeks. The mice were then divided into two groups (n = 5 in each group). The control group mice were injected with 25 mu l of dimethyl sulfoxide and the treatment group mice were injected with 10 mg/kg of analog 315 (in dimethyl sulfoxide, 25 mu l volume) every day for a period of 3 weeks. Animal weights and tumors were measured every week for 3 weeks. At the end of the experimental period, control animals had retained excess fluid, and showed larger tumor sizes compared with the treated group (2.95 vs. 1.67g). A 45% reduction in tumor size and 80% decrease in tumor volume were observed in the treatment group. There was a significant increase in the weights of liver (10%) and spleen (19%) between the control and treated animals. Hematoxylin and Eosin staining of MDA-MB-231 tumor sections revealed more acellular necrotic regions in tumors from the treatment groups compared with the ones from the control group. Ki67, a proliferation marker was higher in number in control tumor section (71.8 +/- 12.8) compared to the treatment tumor section (37.4 +/- 10.4) (P < 0.001). Photomicrographs showed metastatic tumor burden in kidney, lungs, and spleen collected from the control group mice bearing MDA-MB-231 tumors. Treatment group mice showed normal microscopic tissue architecture. Overall, our study showed tumor growth inhibition and antimetastatic effects for the novel ceramide analog 315. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.