diethyl (4-bromobutyl)methylmalonate | 145283-19-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: diethyl (4-bromobutyl)methylmalonate
• 英文别名: diethyl 2-(4-bromobutyl)-2-methylmalonate；diethyl 2-(4-bromobutyl)-2-methylpropanedioate
• CAS: 145283-19-8
• 化学式: C₁₂H₂₁BrO₄
• 分子量: 309.2
• InChiKey: AUUVBGSAGZKWNB-UHFFFAOYSA-N

物化性质

• 沸点：
  315.3±32.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl (4-bromobutyl)methylmalonate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 生成 2-{4-[4-(4-甲氧基-苯基)-哌嗪-1-基]-丁基}-2-甲基-丙烷-1,3-二醇
  参考文献：
  名称：

  Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) Inhibitors. 2. 2-(1,3-Dioxan-2-yl)-4,5-diphenyl-1H-imidazoles as Potent Inhibitors of ACAT

  摘要：

  The second in this series of papers concerns our further investigations into the search for a potent bioavailable acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor suitable for the treatment of atherosclerosis. The design, synthesis, and structure-activity relationship for a series of ACAT inhibitors based on the 2-(1,3-dioxan-2-yl)-4,5-diphenyl-1H-imidazole pharmacophore are described. Compounds such as 13a bearing simple alkyl or hydroxymethyl substituents at the 5-position of the 1,3-dioxane ring are potent bioavailable inhibitors of the rat hepatic microsomal enzyme in vitro (IC50 < 100 nM) but are only weak inhibitors of the human hepatic enzyme. We have found however that 1,3-dioxanes substituted at the 5-cis position with pyrazolylalkyl or aminoalkyl groups are potent inhibitors in vitro of human macrophage ACAT, the potency depending on the nature of the terminal heterocycle and the length of the alkyl chain. An ex vivo bioassay described herein demonstrates that potent inhibitors such as 13t (IC50 = 10 nM) which contain lipophilic terminal heterocycles do not appear to be systemically available. Less potent but more water soluble compounds such as 13h (IC50 = 60 nM) and 13n (IC50 = 70 nM) are absorbed following oral dosing and achieve plasma levels significantly in excess of their IC50 for ACAT inhibition. These compounds are therefore possible candidates for further investigation as oral antiatherosclerotic agents.

  DOI：

  10.1021/jm9505876
• 作为产物：
  描述：

  1,4-二溴丁烷 、 甲基丙二酸二乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 diethyl (4-bromobutyl)methylmalonate
  参考文献：
  名称：

  [EN] KETONE COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES
  [FR] COMPOSES A FONCTION CETONE ET COMPOSITIONS POUR LE CONTROLE DE CHOLESTEROL ET UTILISATIONS ASSOCIEES

  摘要：

  本发明涉及新型酮化合物、含有酮化合物的组合物，以及用于治疗和预防心血管疾病、血脂异常、蛋白异常和葡萄糖代谢紊乱的方法，包括给予含有酮化合物的组合物。该发明的化合物、组合物和方法也适用于治疗和预防阿尔茨海默病、X综合征、过氧化物酶体增殖激活受体相关疾病、败血症、血栓性疾病、肥胖、胰腺炎、高血压、肾脏疾病、癌症、炎症和阳痿。在某些实施例中，该发明的化合物、组合物和方法还适用于与其他治疗药物联合治疗，如降胆固醇和降糖药物。

  公开号：

  WO2005068412A1

文献信息

• Imidazoles
  申请人：RHONE POULENC RORER LIMITED

  公开号：EP0506437A1

  公开（公告）日：1992-09-30

  Imidazole derivatives of the formula: wherein R¹ represents optionally substituted phenyl, R² represents alkyl optionally substituted by hydroxy, X¹ represents a bond, oxygen, -S(0)n-, -CH₂0- or - CH₂N(R⁶)-, wherein n is 0, 1 or 2 and R⁶ represents hydrogen, alkyl, acyl alkylsulphonyl or, -C(X³)NR⁷R⁸, wherein X³ represents oxygen or sulphur and R⁷ and R⁸ represent hydrogen, alkyl, or optionally substituted phenyl, m is zero or 1 to 8, X² represents a bond, oxygen, -S(0)p- wherein p is 0, 1 or 2, or a group -C(0)NR⁴-, -C(S)NR⁴-, -OC(0)NR⁴-, -OC(S)NR⁴-, -NR⁴C(0)- or -NR⁴C(S)-, wherein R⁴ represents hydrogen or alkyl and R³ represents optionally substituted heterocyclyl, or cycloalkyl or, except when X¹ and X² are direct bonds, R³ represents optionally substituted phenyl, or R³ represents amino, alkylamino, benzylamino, benzyl(alkyl)amino, dialkylamino, aminoalkyl, alkylaminoalkyl, benzylaminoalkyl, benzyl(alkyl)aminoalkyl or dialkylaminoalkyl, or a cyclic imino group, and salts thereof possess useful pharmacological properties.

  Imidazole衍生物的化学式如下： 其中R¹代表可选择取代的苯基，R²代表可选择取代的烷基，其上带有羟基，X¹代表键，氧，-S(0)n-，-CH₂0-或- CH₂N(R⁶)-，其中n为0，1或2，R⁶代表氢，烷基，酰基烷基磺酰基或，-C(X³)NR⁷R⁸，其中X³代表氧或硫，R⁷和R⁸代表氢，烷基，或可选择取代的苯基，m为零或1至8，X²代表键，氧，-S(0)p-，其中p为0，1或2，或一个基团-C(0)NR⁴-，-C(S)NR⁴-，-OC(0)NR⁴-，-OC(S)NR⁴-，-NR⁴C(0)-或-NR⁴C(S)-，其中R⁴代表氢或烷基，R³代表可选择取代的杂环烷基，或环烷基或，除非X¹和X²是直接键，R³代表可选择取代的苯基，或R³代表氨基，烷基氨基，苄基氨基，苄(烷基)氨基，二烷基氨基，氨基烷基，烷基氨基烷基，苄基氨基烷基，苄(烷基)氨基烷基或二烷基氨基烷基，或一个环状亚胺基团，及其盐具有有用的药理学性质。
• PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof
  申请人：Mitobridge, Inc.

  公开号：US10188627B2

  公开（公告）日：2019-01-29

  Provided herein are compounds of formula (I) useful for the treatment of PPAR-delta related diseases (e.g. mitochondrial diseases, muscular diseases, vascular diseases, demyelinating diseases and metabolic diseases).

  本文提供的式 (I) 化合物可用于治疗 PPAR-delta 相关疾病（如线粒体疾病、肌肉疾病、血管疾病、脱髓鞘疾病和代谢性疾病）。
• [EN] PPAR AGONISTS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF<br/>[FR] AGONISTES, COMPOSÉS, COMPOSITIONS PHARMACEUTIQUES PPAR ET MÉTHODES D'UTILISATION DE CEUX-CI
  申请人：MITOBRIDGE INC

  公开号：WO2016057660A8

  公开（公告）日：2016-05-19
• AMP Deaminase Inhibitors. 4. Further N3-Substituted Coformycin Aglycon Analogues:  N3-Alkylmalonates as Ribose 5‘-Monophosphate Mimetics
  作者：Brett C. Bookser、Srinivas Rao Kasibhatla、Mark D. Erion

  DOI：10.1021/jm9905413

  日期：2000.4.1

  AMP deaminase (AMPDA) inhibitors increase the levels of extracellular adenosine and preserve intracellular adenylate pools in cellular models of ATP depletion and therefore represent a potential new class of antiischemic drugs. Recently we reported that replacement of the ribose 5'-monophosphate component of the very potent transition-state analogue AMPDA inhibitor coformycin monophosphate (1) with a simple alkylcarboxy group resulted in potent, selective, and cell-penetrating AMPDA inhibitors. Here we report that replacement of this alkylcarboxy group with an a-substituted alkylmalonic acid resulted in enhanced inhibitor potency. The lead compound, 3-(5,5-dicarboxy-6-(3-(trifluoromethyl)phenyl)-n-hexyl)coformation aglycon (21), exhibited an AMPDA K-i of 0.029 mu M which is (3 x 10(5))-fold lower than the K-M for the natural substrate AMP. A comparison of inhibitory potencies shows that the diacid analogues with cr-benzyl substituents are 2-10-fold more inhibitory than similar monoacid-monoester monoester-monoamide, or diester derivatives. Finally, these diacid analogues are 2-40-fold more potent inhibitors than the corresponding monocarboxylates.
• α-cycloalkyl-substituted ω-keto-dicarboxylic acids as lipid regulating agents
  作者：Roel P.L. Bell、Dennis Verdijk、Mike Relou、Dennis Smith、Henk Regeling、Eelco J. Ebbers、Frank M. C. Leemhuis、Daniela C. Oniciu、Clay T. Cramer、Brian Goetz、Michael E. Pape、Brian R. Krause、Jean-Louis Dasseux

  DOI：10.1016/j.bmc.2004.09.046

  日期：2005.1

  A series of cycloalkyl-substituted oxo-alkanedicarboxylic acids have been prepared by the TosMIC methodology departing from haloalkyl-substituted cycloalkylcarboxylic esters. cyclopropyl derivatives showed IC50 activity in the 0.3-1.0 muM range on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes, and they showed lipid-regulating properties when tested in vivo in female obese Zucker fatty rats. (C) 2004 Elsevier Ltd. All rights reserved.