4,5-二氢-2-甲基-4-[2-(4-辛基苯基)乙基]-4-恶唑甲醇 | 402616-28-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4,5-二氢-2-甲基-4-[2-(4-辛基苯基)乙基]-4-恶唑甲醇
• 中文别名: 外泌素
• 英文名称: {2-methyl-4-[2-(4-octylphenyl)ethyl]-4,5-dihydro-1,3-oxazol-4-yl}methanol
• 英文别名: (2-methyl-4-(4-octylphenethyl)-4,5-dihydrooxazol-4-yl)methanol；(+/-)-2-methyl-4-hydroxymethyl-4-(2-(4-octylphenyl)ethyl)oxazoline；4,5-Dihydro-2-methyl-4-[2-(4-octylphenyl)ethyl]-4-oxazolemethanol；[2-methyl-4-[2-(4-octylphenyl)ethyl]-5H-1,3-oxazol-4-yl]methanol
• CAS: 402616-28-8
• 化学式: C₂₁H₃₃NO₂
• 分子量: 331.499
• InChiKey: XJDZZSDQLOHNAO-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于丙酮、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-二氢-2-甲基-4-[2-(4-辛基苯基)乙基]-4-恶唑甲醇 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 2-Amino-4-(4-octylphenyl)-2-(phenylmethoxymethyl)butan-1-ol
  参考文献：
  名称：

  Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Vα19 NKT cell with α-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit

  摘要：

  A 2-substituted 2-aminopropane-1,3-diol or 2-aminoethanol is the minimum structure required for the immunosuppressive activity of ISP-I, an antibiotic isolated from the culture broth of Isaria sinclairil. A series of alpha-mannosyl ceramide (alpha-ManCer) analogues was derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols in place of sphingosine. The newly synthesized glycosides were evaluated for their effects on immune responses. In contrast to the immunosuppressive activity of the precursors, the a-ManCer analogues induced immunopromotive responses from invariant V alpha N-J alpha 26 transgenic mouse lymphocytes more effectively than the original a-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the alpha-ManCer analogues so that they potentially acquire specific antigenicity toward V alpha 19 NKT cell, a novel NKT cell subset. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.11.013
• 作为产物：
  描述：

  原乙酸三乙酯 、 2-氨基-2-[2-(4-辛基苯基)乙基]-1,3-丙二醇 在 二乙基异丙基胺 作用下， 生成 4,5-二氢-2-甲基-4-[2-(4-辛基苯基)乙基]-4-恶唑甲醇
  参考文献：
  名称：

  Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Vα19 NKT cell with α-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit

  摘要：

  A 2-substituted 2-aminopropane-1,3-diol or 2-aminoethanol is the minimum structure required for the immunosuppressive activity of ISP-I, an antibiotic isolated from the culture broth of Isaria sinclairil. A series of alpha-mannosyl ceramide (alpha-ManCer) analogues was derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols in place of sphingosine. The newly synthesized glycosides were evaluated for their effects on immune responses. In contrast to the immunosuppressive activity of the precursors, the a-ManCer analogues induced immunopromotive responses from invariant V alpha N-J alpha 26 transgenic mouse lymphocytes more effectively than the original a-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the alpha-ManCer analogues so that they potentially acquire specific antigenicity toward V alpha 19 NKT cell, a novel NKT cell subset. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.11.013

文献信息

• Phosphate derivatives as immunoregulatory agents
  申请人：——

  公开号：US20020091105A1

  公开（公告）日：2002-07-11

  Immunoregulatory compounds are disclosed of the formula: 1 and 2 as well as the pharmaceutically acceptable salts and hydrates thereof, are disclosed. The compounds are useful for treating immune mediated diseases and conditions, such as bone marrow, organ and tissue transplant rejection. Pharmaceutical compositions and methods of use are included.

  揭示了具有以下式子的免疫调节化合物：1和2以及其药用盐和水合物。这些化合物可用于治疗免疫介导的疾病和状况，如骨髓、器官和组织移植排斥。包括药物组成和使用方法。
• Effects of Phosphorylation of Immunomodulatory Agent FTY720 (Fingolimod) on Antiproliferative Activity against Breast and Colon Cancer Cells
  作者：Yasuo Nagaoka、Kota Otsuki、Tetsuro Fujita、Shinichi Uesato

  DOI：10.1248/bpb.31.1177

  日期：——

  FTY720 (fingolimod), a novel immunosuppressant, was found to become biologically activated by phosphorylation into FTY720-1-phosphate (FTY720-P), which is a high-affinity agonist for sphingosine-1-phosphate (sphingosine-1-P)-receptors. FTY720 has also been reported to have a strong antitumor activity. The association between the phosphorylation of FTY720 and the growth inhibition of FTY720 against cancer cells are still not completely understood. In this study, we investigated the effects of FTY720, sphingosine, and their related compounds on the proliferation of human breast cancer cell lines (MCF-7, MDA-MB-231 and Sk-Br-3) and human colon cancer cell lines (HCT-116 and SW620). Non-phosphorylated FTY720, sphingosine and an FTY720 derivative, ISP-I-55, showed significant growth inhibition against these cells, with IC50 values of 5—20 μM at 48 h post-drug treatment. We confirmed that FTY720 induces the activation of a major mitogen-activated protein kinase, JNK, without the activation of p38 and down-regulation of phospho-ERK in MCF-7 breast cancer cells. In contrast, the phosphorylated derivatives, FTY720-P and sphingosine-1-P, as well as a phosphinane FTY720 derivative, cFTY720-P, did not inhibit the growth of the cells in the concentration range of 5—50 μM, whereas FTY720-P and sphingosine-1-P slightly induced the growth of MCF-7 cells. Combining FTY720 with dimethylsphingosine, a sphingosine kinase inhibitor, augmented the inhibitory effect of FTY720. These results indicate that the antiproliferative activity of FTY720 does not result from its phosphorylation, either endogenous or exogenous.

  研究发现，FTY720（芬戈莫德）是一种新型免疫抑制剂，可通过磷酸化成为 FTY720-1-磷酸（FTY720-P）而被生物激活，FTY720-1-磷酸（FTY720-P）是鞘氨醇-1-磷酸（鞘氨醇-1-P）受体的高亲和性激动剂。据报道，FTY720 还具有很强的抗肿瘤活性。FTY720 的磷酸化与 FTY720 抑制癌细胞生长之间的关系尚未完全明了。在这项研究中，我们研究了 FTY720、鞘氨醇及其相关化合物对人类乳腺癌细胞系（MCF-7、MDA-MB-231 和 Sk-Br-3）和人类结肠癌细胞系（HCT-116 和 SW620）增殖的影响。非磷酸化的 FTY720、鞘氨醇和 FTY720 衍生物 ISP-I-55 对这些细胞的生长有显著的抑制作用，在药物处理后 48 小时的 IC50 值为 5-20 μ<小>M。我们证实，在 MCF-7 乳腺癌细胞中，FTY720 可诱导激活一种主要的丝裂原活化蛋白激酶 JNK，而不会激活 p38 和下调磷酸-ERK。相比之下，磷酸化衍生物 FTY720-P 和鞘氨醇-1-P 以及膦酰 FTY720 衍生物 cFTY720-P 在 5-50 μM浓度范围内并不抑制细胞的生长，而 FTY720-P 和鞘氨醇-1-P 则会轻微诱导 MCF-7 细胞的生长。将 FTY720 与鞘氨醇激酶抑制剂二甲基鞘氨醇结合使用可增强 FTY720 的抑制作用。这些结果表明，FTY720 的抗增殖活性并不是由其磷酸化（无论是内源性还是外源性）引起的。
• Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Vα19 NKT cell with α-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit
  作者：Michio Shimamura、Naoki Okamoto、Yi-Ying Huang、Jouji Yasuoka、Kenji Morita、Akira Nishiyama、Yuusuke Amano、Tadashi Mishina

  DOI：10.1016/j.ejmech.2005.11.013

  日期：2006.5

  A 2-substituted 2-aminopropane-1,3-diol or 2-aminoethanol is the minimum structure required for the immunosuppressive activity of ISP-I, an antibiotic isolated from the culture broth of Isaria sinclairil. A series of alpha-mannosyl ceramide (alpha-ManCer) analogues was derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols in place of sphingosine. The newly synthesized glycosides were evaluated for their effects on immune responses. In contrast to the immunosuppressive activity of the precursors, the a-ManCer analogues induced immunopromotive responses from invariant V alpha N-J alpha 26 transgenic mouse lymphocytes more effectively than the original a-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the alpha-ManCer analogues so that they potentially acquire specific antigenicity toward V alpha 19 NKT cell, a novel NKT cell subset. (c) 2006 Elsevier SAS. All rights reserved.