CAS: 119567-63-4; (2S,3R,E)-2-(Dimethylamino)Octadec-4-Ene-1,3-Diol

📜聚合甲醛,D-赤式-鞘氨醇盐酸盐置于sodium Cyanoborohydride体系中,用 甲醇 用作溶剂,化学反应 12.0H,以62%的收率获得n,N-二甲基鞘胺醇
参考文献:手性 N,N-二甲基鞘氨醇对神经生长因子与原肌球蛋白受体激酶 A 相互作用的评价
标题:手性 N,N-二甲基鞘氨醇对神经生长因子与原肌球蛋白受体激酶 A 相互作用的评价
摘要:神经性疼痛是由神经系统损伤引起的难以忍受的病症.作为不同的急性疼痛,神经性疼痛是慢性的,它严重影响生活质量.N,N-二甲基-D-赤型-鞘氨醇 (Dms) 是一种神经性疼痛诱导剂,由鞘氨醇从头代谢.在最近的一项研究中,代谢组学显示神经性疼痛小鼠脊髓中 Dms 的浓度水平升高.神经生长因子 (Ngf) 是与原肌球蛋白受体激酶 A (Trka) 相互作用的周围神经系统靶向疼痛因子之一.基于这些信息,我们对 Dms 可能通过增加 Ngf 活性诱导神经性疼痛样行为的可能性感兴趣.在这项研究中,我们发现 Dms 可以增强 Ngf 与 Trka 的结合,然后促进表皮神经纤维的神经突生长和 Trka 的磷酸化.此外,一种立体异构体,N,N-二甲基-L-赤型-鞘氨醇,没有任何显示出这样的生物活性.结果表明,Dms 可以增强 Ngf 与 Trka 的结合,并且其立体化学是展示其活性的重要因素.
Doi:10.1002/chir.23433

专利信息

专利号:US-2005182020-A1
优先权日:2003-11-14
标题 :Ceramide de novo synthesis-based therapeutic and prophylactic methods, and related articles of manufacture
发明人：WORGALL TILLA S; DECKELBAUM RICHARD J
摘要:Described is a method for decreasing the amount of mSREBP in a cell characterized by an elevated level of mSREBP comprising contacting the cell with an agent that specifically inhibits de novo synthesis of ceramide in the cell, thereby decreasing the amount of mSREBP in the cell. Also described are related methods and articles of manufacture.

专利号:US-6368831-B1
优先权日:1998-06-29
标题 :Treatment of hyperproliferative disorders
发明人：MAURER BARRY J; REYNOLDS C PATRICK
权利人:LOS ANGELES CHILDRENS HOSPITAL
摘要:A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-generating retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) ceramide degredation inhibitor, such as compounds selected from the group consisting of (i) glucosylceramide synthesis inhibitors and/or 1-acylceramide synthesis inhibitors, (ii) sphingosine-1-phosphate synthesis inhibitors, and (iii) protein kinase C inhibitors. A preferred glucosyl ceramide synthesis inhibitor is 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingosine-1-phosphate synthesis inhibitor is D-erythro-N,N-dimethylsphingosine. A preferred protein kinase C inhibitor is L-threo-dihydrosphingosine.

专利号:US-6352844-B1
优先权日:1998-06-29
标题:Treatment of hyperproliferative disorders
发明人：MAURER BARRY J; CABOT MYLES; REYNOLDS C PATRICK
权利人:LOS ANGELES CHILDRENS HOSPITAL; WAYNE JOHN CANCER INST
摘要:A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-generating retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) ceramide degredation inhibitor, such as compounds selected from the group consisting of (i) glucosylceramide synthesis inhibitors, (ii) sphingosine-1-phosphate synthesis inhibitors, and (iii) protein kinase C inhibitors. A preferred glucosyl ceramide synthesis inhibitor is 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingosine-1-phosphate synthesis inhibitor is D-erythro-N,N-dimethylsphingosine. A preferred protein kinase C inhibitor is L-threo-dihydrosphingosine.

专利号:US-9687477-B2
优先权日:2011-06-01
标 题 :Modulation of sphingosine 1-phosphate metabolizing enzymes for the treatment of negative-strand RNA virus infections
发明人：HAHM BUMSUK; SEO YOUNG-JIN; ALEXANDER STEPHEN; MADHUVANTHI VIJAYAN
权利人:HAHM BUMSUK; SEO YOUNG-JIN; ALEXANDER STEPHEN; MADHUVANTHI VIJAYAN; UNIV MISSOURI
摘要:The present invention relates to compounds and methods for the prevention or treatment of infections by negative strand RNA viruses, such as influenza virus and measles virus, wherein said compounds delay or inhibit viral replication by modulating the level or activity of a polypeptide involved in the synthesis or degradation of sphingosine-1-phosphate (S1P) in a cell, tissue, or subject. The methods involve administration of one or more compounds which modulate the level of gene expression, where the gene encodes a polypeptide involved in regulating the metabolic level of S1P, or modulate the level or activity of a polypeptide involved in regulating the metabolic level of S1P, such as sphingosine kinase (SK) and S1P lyase (SPL). Exemplary methods are directed towards reducing the level of SW by reducing the level or activity of one or more SKs, increasing the level or activity of one or more SPLs, or a combination of both steps.

专利号:US-10584156-B2
优先权日:2015-03-13
标 题:Insulin analogues with a glucose-regulated conformational switch
发明人：WEISS MICHAEL
权利人:UNIV CASE WESTERN RESERVE
摘要:A two-chain insulin analogue contains an A chain modified by (i) a monomeric glucose-binding element at or near its N terminus and (ii) a B chain modified by at or near its C terminus by an element that reversibly binds to the monomeric glucose-binding element such that this linkage is displaceable by glucose. The monomeric glucose-binding element may be phenylboronic acid derivative (optionally halogenated). The B chain may be modified by a diol-containing element derived from a monosaccharide, disaccharide or oligosaccharide, a non-saccharide diol-containing moiety or a α-hydroxycarboxylate-containing moiety. The analogue can be manufactured by trypsin-mediated semi-synthesis. Formulations can be at strengths U-10 to U-1000 in soluble solutions at pH 7.0-8.0 with or without zinc ions at a molar ratio of 0.0-3.0 ions per insulin analogue monomer. A patient with diabetes mellitus may be treated with subcutaneous, intraperitoneal, or oral administration of a physiologically effective amount of the insulin analogue.