aminoglutarimide trifluoroacetate | 284495-32-5

• 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: aminoglutarimide trifluoroacetate
• 英文别名: (S)-glutarimidyl-3-ammonium trifluoroacetate；3-aminopiperidine-2,6-dione trifluoroacetic acid；(3S)-3-aminopiperidine-2,6-dione;2,2,2-trifluoroacetic acid
• CAS: 284495-32-5
• 化学式: C₂HF₃O₂*C₅H₈N₂O₂
• 分子量: 242.155
• InChiKey: IOLMYDDAHXTLLS-DFWYDOINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.62
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  aminoglutarimide trifluoroacetate 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、800.01 kPa 条件下， 反应 64.0h， 生成 2'-(4-(N-(N-tert-butyloxycarbonyl)propylamino)phthaloyl)glutarimide
  参考文献：
  名称：

  沙利度胺衍生物治疗神经炎症

  摘要：

  沙利度胺的确切作用机制仍不确定，并且在疾病之间以及在不同的临床条件下可能会有所不同。单独或与已确立的疗法联合用于治疗多种炎性和自身免疫性疾病，以及用作抗癌剂，显然沙利度胺及其衍生物值得进一步研究。特别地，沙利度胺在多发性硬化症（MS）的小鼠模型中是有效的，MS是一种自身免疫性炎性疾病，称为实验性自身免疫性脑脊髓炎（EAE）。在这里，我们描述了在邻苯二甲酰亚胺环上带有氨基烷基的沙利度胺的新大分子前药的合成和初步生物学评估。研究了这些化合物限制EAE的有效性，结果表明，-1沙利度胺等效剂量，他们废除了EAE的临床和病理特征。

  DOI：

  10.1002/cmdc.201000326
• 作为产物：
  描述：

  谷氨酸二甲酯 在 4-二甲氨基吡啶 、 sodium amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 17.5h， 生成 aminoglutarimide trifluoroacetate
  参考文献：
  名称：

  A Practical and Efficient Synthesis of Thalidomide via Na/Liquid NH₃ Methodology¹

  摘要：

  A facile, efficient, concise, cost-effective, and scalable synthesis of thalidomide in high overall yield (55%) is presented. Treatment of Boc-protected L-glutamic acid diester via Na/ liquid (liq.) NH3 (-33 degrees C) mediated cyclization methodology produces a corresponding glutarimide ring which was subsequently condensed with phthalic anhydride in the presence of glacial acetic acid to afford thalidomide.

  DOI：

  10.1021/op050129z

文献信息

• 5H-THIOENO(3,4-c)PYRROLE-4,6-DIONE DERIVATIVES AND THEIR USE AS TUMOR NECROSIS FACTOR INHIBITORS
  申请人：ZHANG Hesheng

  公开号：US20080176900A1

  公开（公告）日：2008-07-24

  Taught are derivatives of 5H-thioeno(3,4- c )pyrrole-4,6-dione, their organic, and inorganic salts, methods of synthesis of these derivatives, and their application as active pharmaceutical-ingredients useful as inhibitors of TNFα, the derivative being represented by the general formula (I): in which R 1 represents H, C 1-6 alkyl, OR 4 , OC(O)R 5 , NO 2 , NHC(O)R 6 , or NR 7 R 8 ; R 2 represents H, a halogen, or C 1-6 alkyl; R 3 represents H, methyl, isopropyl, allyl, benzyl, CH 2 CO 2 (C 1-6 alkyl), or CH 2 (CH 2 ) n R 9 ; R 4 , R 5 , R 6 , R 7 , and R 8 each independently and at each occurrence represents H, or C 1-6 alkyl; R 9 represents H, C 1-6 alkyl, OH, OC 1-6 alkyl, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , or CO 2 (C 1-6 alkyl); and n represents 1, 2, 3, or 4.

  本发明涉及5H-噻烯[3,4-c]吡咯-4,6-二酮的衍生物，它们的有机盐和无机盐，这些衍生物的合成方法，以及它们作为抑制TNFα的活性药物成分的应用，所述衍生物由通式(I)表示： 其中R1代表H，C1-6烷基，OR4，OC(O)R5，NO2，NHC(O)R6或NR7R8；R2代表H，卤素或C1-6烷基；R3代表H，甲基，异丙基，烯丙基，苄基，CH2CO2(C1-6烷基)或CH2(CH2)nR9；R4、R5、R6、R7和R8每个独立地并且在每次出现时代表H或C1-6烷基；R9代表H，C1-6烷基，OH，OC1-6烷基，NH2，NHC1-6烷基，N(C1-6烷基)2或CO2(C1-6烷基)；n代表1、2、3或4。
• Compounds and methods to inhibit or augment an inflammatory response
  申请人：Cambridge University Technical Services Ltd.

  公开号：US07238711B1

  公开（公告）日：2007-07-03

  Isolated and purified chemokine peptides, variants, and derivatives thereof, as well as chemokine peptide analogs, are provided.

  提供了分离和纯化的趋化因子肽、变异体及其衍生物，以及趋化因子肽类似物。
• Immunosuppressive but Non-LasR-Inducing Analogues of the <i>Pseudomonas aeruginosa</i> Quorum-Sensing Molecule <i>N</i>-(3-Oxododecanoyl)-<scp>l</scp>-homoserine Lactone
  作者：Gopal P. Jadhav、Siri Ram Chhabra、Gary Telford、Doreen S. W. Hooi、Karima Righetti、Paul Williams、Barrie Kellam、David I. Pritchard、Peter M. Fischer

  DOI：10.1021/jm2001019

  日期：2011.5.12

  The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone (1) is involved not only in bacterial activation but also in subversion of the host immune system, and this compound might thus be used as a template to design immunosuppressive agents, provided derivatives devoid of quorum-sensing activity could be discovered. By use of a leukocyte proliferation assay and a newly developed bioluminescent P. aeruginosa reporter assay, systematic modification of 1 allowed us to delineate the bacterial LasR-induction and host immunosuppressive activities. The main determinant is replacement of the methylene group proximal to the beta-ketoamide in the acyl chain of 1 with functions containing heteroatoms, especially an NH group. This modification can be combined with replacement of the homoserine lactone system in 1 with stable cyclic groups. For example, we found the simple compound N(1)-(5-chloro-2-hydroxyphenyl)-N(3)-octylmalonamide (25d) to be over twice as potent as 1 as an immune suppressor while displaying LasR-induction antagonist activity.
• De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives
  作者：Christopher Heim、Dimanthi Pliatsika、Farnoush Mousavizadeh、Kerstin Bär、Birte Hernandez Alvarez、Athanassios Giannis、Marcus D. Hartmann

  DOI：10.1021/acs.jmedchem.9b00454

  日期：2019.7.25

  Targeted protein degradation via cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase complex, is an increasingly important strategy in various clinical settings, in which the substrate specificity of CRBN is altered via the binding of small-molecule effectors. To date, such effectors are derived from thalidomide and confer a broad substrate spectrum that is far from being fully characterized. Here, we employed a rational and modular approach to design novel and minimalistic CRBN effectors. In this approach, we took advantage of the binding modes of hydrolyzed metabolites of several thalidomide-derived effectors, which we elucidated via crystallography. These yielded key insights for the optimization of the minimal core binding moiety and its linkage to a chemical moiety that imparts substrate specificity. Based on this scaffold, we present a first active de-novo CRBN effector that is able to degrade the neo-substrate IKZF3 in the cell culture.
• Thiothalidomides:  Novel Isosteric Analogues of Thalidomide with Enhanced TNF-α Inhibitory Activity
  作者：Xiaoxiang Zhu、Tony Giordano、Qian-sheng Yu、Harold W. Holloway、Tracy Ann Perry、Debomoy K. Lahiri、Arnold Brossi、Nigel H. Greig

  DOI：10.1021/jm030152f

  日期：2003.11.1

  Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and mutiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-a secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity.