OMDM-169 | 130193-44-1

• 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: OMDM-169
• 英文别名: (2S,3S,4S)-formylamino-acetic acid 1-(3-hexyl-4-oxo-oxetan-2-ylmethyl) dodecyl ester；N-formyl-glycine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester；(2S,3S,4S)-formylamino-acetic acid 1-(3-hexyl-4-oxo-oxetan-2-ylmethyl)-dodecyl ester；Orlistat derivative, 17c；[(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] 2-formamidoacetate
• CAS: 130193-44-1
• 化学式: C₂₅H₄₅NO₅
• 分子量: 439.636
• InChiKey: ANPULBVRORHAGO-VABKMULXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  31
• 可旋转键数：
  21
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

OMDM169是一种强效且选择性的MAGL抑制剂，能够提高2-AG水平，并通过间接激活大麻素受体发挥镇痛作用。在大鼠小脑和COS-7细胞中，OMDM169对2-AG水解活性的IC50值介于0.13微摩尔到0.41微摩尔之间；同时，在人重组MAGL中，其IC50值为0.89微摩尔。此外，OMDM169对人CB1和CB2受体无活性（Ki值大于10微摩尔）。

反应信息

• 作为产物：
  描述：

  glycine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 、 甲乙酐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以21%的产率得到OMDM-169
  参考文献：
  名称：

  Tetrahydrolipstatin Analogues as Modulators of Endocannabinoid 2-Arachidonoylglycerol Metabolism

  摘要：

  formation or hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Three of the novel compounds, i.e., 11, 13, and 15, inhibited 2-AG formation via the diacylglycerol lipase a (DAGL alpha) with IC50 values lower than 50 nM (IC50 of THL = 1 mu M) and were between 23- and 375-fold selective vs 2-AG hydrolysis by rnonoacylglycerol lipase (MAGL) Lis well as vs cannabinoid CB1 and CB2 receptors and anandamide hydrolysis by fatty acid amide hydrolase (FAAH). Three other THL analogues, i.e., 14, 16, and 18, were slightly more potent than THL against DAGL alpha and appreciably selective vs MAGL, CB receptors, and FAAH (15-26-fold). One compound, i.e., 8, was a potent inhibitor of MAGL-like activity (IC50 = 0.41 mu M), and relatively (similar to 7-fold) selective vs the other targets tested.

  DOI：

  10.1021/jm800978m

文献信息

• BETA-LACTONE COMPOUNDS
  申请人：Smith Jeffrey W.

  公开号：US20090124681A1

  公开（公告）日：2009-05-14

  The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R 1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

  本发明提供具有一般结构A的化合物，或其药学上可接受的衍生物：其中R是烷基基团，R1包括至少一种从烷基、烯基、芳基、杂环、羟基、酯、酰胺、醛基和卤素组成的基团。
• Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase
  作者：Robyn D. Richardson、Gil Ma、Yatsandra Oyola、Manuel Zancanella、Lynn M. Knowles、Piotr Cieplak、Daniel Romo、Jeffrey W. Smith

  DOI：10.1021/jm800321h

  日期：2008.9.11

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.
• BARBIER, PIERRE;SCHNEIDER, FERNAND;WIDMER, ULRICH
  作者：BARBIER, PIERRE、SCHNEIDER, FERNAND、WIDMER, ULRICH

  DOI：——

  日期：——
• Oxetanone
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0185359B1

  公开（公告）日：1991-12-04
• US8258321B2
  申请人：——

  公开号：US8258321B2

  公开（公告）日：2012-09-04