4-溴-3-氧代戊酸甲酯 | 105983-77-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 4-溴-3-氧代戊酸甲酯
• 英文名称: methyl 4-bromo-3-oxopentanoate
• CAS: 105983-77-5
• 化学式: C₆H₉BrO₃
• 分子量: 209.04
• InChiKey: HCBQTGAZENNMLM-UHFFFAOYSA-N

物化性质

• 沸点：
  224.1±15.0 °C(Predicted)
• 密度：
  1.474±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2918300090
• 包装等级：
  III
• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P270,P280,P301+P330+P331,P303+P361+P353,P304+P340,P305+P351+P338,P310,P363,P405,P501
• 危险品运输编号：
  3265
• 危险性描述：
  H302,H314
• 储存条件：
  | 室温 |

反应信息

• 作为反应物：
  描述：

  4-溴-3-氧代戊酸甲酯 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 1.5h， 生成 2-(5-甲基-2-苯基-1,3-恶唑-4-基)乙基甲烷磺酸酯
  参考文献：
  名称：

  Synthesis and antimicrobial evaluation of 3-methanone-6-substituted-benzofuran derivatives

  摘要：

  Seventeen benzofuran derivatives were synthesized and screened for their antibacterial activities against Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Seven of them have showed excellent antibacterial activities compared to the positive controls (Cefotaxime and Sodium Penicillin). The substitutions at C-6 and C-3 positions of these derivatives were found to greatly impact on the antibacterial activity and strains specificity, respectively. Specifically, compounds bearing a hydroxyl group at C-6 (5a, 5b, 5c and 12) offered excellent antibacterial activities against all five above-mentioned strains (MIC80 = 0.78-12.5 ug/mL), and those with imine (15) and (3, 4, 5-trimethoxyphenyl) methanone (7e), respectively, at C-3 position showed selective activity against S. aureus among five tested strains with great MIC80 values (3.12-12.5 ug/mL). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.013
• 作为产物：
  描述：

  3-氧代戊酸甲酯 在 溴 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到4-溴-3-氧代戊酸甲酯
  参考文献：
  名称：

  Design and Synthesis of 3-(2-Ethyl-4-{2-[2-(4-fluorophenyl)-5-methyloxazol-4-yl]ethoxy}phenyl)propanoic Acid: A Novel Triple-acting PPARα, -γ, and -δ Agonist

  摘要：

  本文描述了三重作用PPARα、-γ和-δ激动剂3-(2-乙基-4-{2-[2-(4-氟苯基)-5-甲基噁唑-4-基]乙氧基}苯基)丙酸(1a)的设计与合成。该化合物具有强大的三重作用PPARα、-γ和-δ激动剂特性，其EC50值分别为0.029、0.013和0.029 µM。合成路线以噁唑环的合成为关键步骤，从市售的3-氧代戊酸甲酯和3-羟基苯乙酮出发，最终得到目标化合物1，总产率为32%。

  DOI：

  10.1246/cl.2012.406

文献信息

• 2-Acyl-3-carboxyl-tetrahydroisoquinoline Derivatives: Mixed-Type PTP1B Inhibitors without PPARγ Activation
  作者：Ko Morishita、Yoshimichi Shoji、Masaki Fukui、Yuma Ito、Tatsuya Kitao、Shin-ichiro Ozawa、Shuichi Hirono、Hiroaki Shirahase

  DOI：10.1248/cpb.c18-00571

  日期：2018.12.1

  oquinoline derivatives were synthesized and biologically evaluated. Among them, (S)-2-(E)-3-furan-2-ylacryloyl}-7-[(2E,4E)-5-(2,4,6-trifluorophenyl)penta-2,4-dienyloxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (compound 17u) was identified as a potent protein tyrosine phosphatase 1B (PTP1B) inhibitor without peroxisome proliferator-activated receptor (PPAR) γ activation: PTP1B inhibition IC50=0

  合成了一系列新颖的2-酰基-3-羧基-四氢异喹啉衍生物，并对其进行了生物学评估。其中，（S）-2-（（E）-3-呋喃-2-基丙烯酰基）-7-[（2E，4E）-5-（2,4,6-三氟苯基）戊-2,4-二烯氧基] -1,2,3,4-四氢异喹啉-3-羧酸（化合物17u）被确定为有效的蛋白酪氨酸磷酸酶1B（PTP1B）抑制剂，无过氧化物酶体增殖物激活受体（PPAR）γ激活：PTP1B抑制作用IC50 = 0.19 µM，PPARγEC50> 10 µM。化合物17u对PTP1B表现出混合型抑制作用，这种抑制模式通过计算配体对接到PTP1B的催化位点和变构位点而得以合理化。化合物17u在大鼠中也表现出较高的口服吸收，剂量为10 mg / kg（每os（口服），Cmax = 4.67 µM），在以db的最终给药后24小时进行的口服葡萄糖耐量试验中，在30 mg / kg / d（po）下连续4周显着
• DPP IV inhibitors
  申请人：——

  公开号：US20030130281A1

  公开（公告）日：2003-07-10

  The present invention relates to compounds of formula (I) 1 wherein R 1 , R 2 , and X are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV, such as diabetes, particularly non-insulin dependent diabetes mellitus, and impaired glucose tolerance.

  本发明涉及以下式（I）的化合物： 其中R1、R2和X如描述和权利要求中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与DPP IV相关的疾病，如糖尿病，特别是非胰岛素依赖型糖尿病和糖耐量受损。
• [EN] AROMATIC RING COMPOUND<br/>[FR] COMPOSÉ À NOYAU AROMATIQUE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013125732A1

  公开（公告）日：2013-08-29

  The present invention provides a compound having a GOAT inhibitory action, which is useful for the prophylaxis or treatment of obesity and the like, and has superior efficacy. The present invention is a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种具有GOAT抑制作用的化合物，该化合物用于预防或治疗肥胖等疾病，并具有优异的疗效。本发明的化合物由式(I)表示：其中每个符号如说明书中所定义，或其盐。
• Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation
  申请人：——

  公开号：US20030216391A1

  公开（公告）日：2003-11-20

  This invention relates to novel indane acetic acid derivatives which are useful in the treatment of diseases such as diabetes, obesity, hyperlipidemia, and atherosclerotic diseases. The invention also relates to intermediates useful in preparation of indane acetic derivatives and to methods of preparation.

  这项发明涉及新颖的茚基乙酸衍生物，可用于治疗糖尿病、肥胖症、高脂血症和动脉粥样硬化等疾病。该发明还涉及用于制备茚基乙酸衍生物的中间体以及制备方法。
• A Novel Series of (S)-2,7-Substituted-1,2,3,4-tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor .ALPHA./.GAMMA. Dual Agonists with Protein-Tyrosine Phosphatase 1B Inhibitory Activity
  作者：Kazuya Otake、Satoru Azukizawa、Masaki Fukui、Michiko Shibabayashi、Hikaru Kamemoto、Tomohiro Miike、Kazuyoshi Kunishiro、Masayasu Kasai、Hiroaki Shirahase

  DOI：10.1248/cpb.59.1233

  日期：——

  Novel 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-7-(2-2-[(E)-2-cyclopentylvinyl]-5-methyloxazol-4-yl}ethoxy)-2-[(2E,4E)-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14c) was identified as a peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist. The transactivation activity of 14c was comparable to that of rosiglitazone in human PPARγ (EC50=0.14 μM) and was much higher than in human PPARα (EC50=0.20 μM). In addition, 14c, but not rosiglitazone, showed human protein-tyrosine phosphatase 1B (PTP-1B) inhibitory activity (IC50=1.85 μM). 14c showed about 10-fold stronger hypoglycemic and hypotriglyceridemic effects than rosiglitazone by repeated application for 14 d in male KK-Ay mice. Furthermore, 14c, but not rosiglitazone, increased hepatic peroxisome acyl CoA oxidase activity at 30 mg/kg/d for 7 d in male Syrian hamsters, probably due to its PPARα agonist activity. 14c did not affect plasma volume at 100 mg/kg/d for 14 d in male ICR mice, while rosiglitazone significantly increased it. In conclusion, 14c is a promising candidate for an efficacious and safe anti-diabetic drug with triple actions as a PPARα/γ dual agonist with PTP-1B inhibitory activity.

  合成了新型1,2,3,4-四氢异喹啉-3-羧酸衍生物，并鉴定出(S)-7-(2-2-[(E)-2-环戊基乙烯]-5-甲氧基噁唑-4-基}乙氧基)-2-[(2E,4E)-己二烯酰]-1,2,3,4-四氢异喹啉-3-羧酸(14c)作为过氧化物酶体增殖物激活受体(PPAR)α/γ双重激动剂。14c的转激活活性与人类PPARγ的罗格列酮相当（EC50=0.14 μM），而在PPARα中的活性则明显高于罗格列酮（EC50=0.20 μM）。此外，14c显示出对人类蛋白酪氨酸磷酸酶1B(PTP-1B)的抑制活性（IC50=1.85 μM），而罗格列酮则没有。14c在对雄性KK-Ay小鼠进行14天的重复给药中，显示出比罗格列酮强约10倍的降血糖及降低甘油三酯效果。此外，14c在雄性叙利亚仓鼠中以30 mg/kg/d剂量连续7天应用时，增加了肝脏过氧化物酶体酰基辅酶A氧化酶的活性，这可能与其PPARα激动剂活性有关。而14c在雄性ICR小鼠的100 mg/kg/d剂量下连续14天的实验中未对血浆体积产生影响，而罗格列酮则显著增加了血浆体积。总之，14c作为一种PPARα/γ双重激动剂并具有PTP-1B抑制活性，是一种有前景的有效且安全的抗糖尿病药物候选者。