methyl 3-(4-hydroxyohenyl)-2-methylpropionate | 81579-29-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-(4-hydroxyohenyl)-2-methylpropionate
• 英文别名: methyl 3-(4-hydroxyphenyl)-2-methylpropanoate；(+/-)-3-(4-hydroxy-phenyl)-2-methyl-propionic acid methyl ester
• CAS: 81579-29-5
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: WRKKBDIQKYNZTJ-UHFFFAOYSA-N

物化性质

• 沸点：
  83-87 °C(Press: 0.64 Torr)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-hydroxyohenyl)-2-methylpropionate 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 4.0h， 生成 3-[4-(7-Chloroquinoxalin-2-yl)oxyphenyl]-2-methylpropanoic acid
  参考文献：
  名称：

  Synthetic modification of the 2-oxypropionic acid moiety in 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469), and consequent antitumor effects. Part 4

  摘要：

  The criteria for the activity of 2-{4-[(7-chloro-2 -quinoxalinyl)oxy]phenoxy}propionic acid (XK469) and 2-{4-[(7-bromo-2-quinolinyl)oxy]phenoxy} propionic acid (SH80) against transplanted tumors in mice established in previous studies, require a (7-halo-2-quinoxalinoxy)- or a (7-halo-2-quinolinoxyl)-residue, respectively, bridged via a 1,4-OC6H4O-linker to C-2 of propionic acid. The present work demonstrates that substitution of fluorine at the 3-position of the 1,4-OC6H4O-linker of XK469 leads to a 10-fold reduction in activity, whereas the corresponding 2-fluoro analog proved to be 100-fold less active than XK469. Moreover, the latter tolerated substitution of but a single, additional methyl group to the 2-position of the propionic acid moiety, that is, the isobutyric acid analog, without loss of significant in vivo activity. Indeed, an intact 2-oxypropionic acid moiety is a prerequisite for maximum antitumor activity of 1a. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.011
• 作为产物：
  描述：

  (E)-3-(4-hydroxyphenyl)-2-methylacrylic acid 在 sodium hydroxide 、 aluminium-nickel alloy 、 硫酸 作用下， 以 水 为溶剂， 生成 methyl 3-(4-hydroxyohenyl)-2-methylpropionate
  参考文献：
  名称：

  Synthetic modification of the 2-oxypropionic acid moiety in 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469), and consequent antitumor effects. Part 4

  摘要：

  The criteria for the activity of 2-{4-[(7-chloro-2 -quinoxalinyl)oxy]phenoxy}propionic acid (XK469) and 2-{4-[(7-bromo-2-quinolinyl)oxy]phenoxy} propionic acid (SH80) against transplanted tumors in mice established in previous studies, require a (7-halo-2-quinoxalinoxy)- or a (7-halo-2-quinolinoxyl)-residue, respectively, bridged via a 1,4-OC6H4O-linker to C-2 of propionic acid. The present work demonstrates that substitution of fluorine at the 3-position of the 1,4-OC6H4O-linker of XK469 leads to a 10-fold reduction in activity, whereas the corresponding 2-fluoro analog proved to be 100-fold less active than XK469. Moreover, the latter tolerated substitution of but a single, additional methyl group to the 2-position of the propionic acid moiety, that is, the isobutyric acid analog, without loss of significant in vivo activity. Indeed, an intact 2-oxypropionic acid moiety is a prerequisite for maximum antitumor activity of 1a. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.011

文献信息

• C-Terminally Pegylated Growth Hormones
  申请人：Zundel Magali

  公开号：US20090105134A1

  公开（公告）日：2009-04-23

  Conjugated growth hormones of the structure (I) are provided together with methods for manufacturing said conjugates. The conjugates are useful in therapy.

  提供具有结构（I）的共轭生长激素以及制造所述共轭物的方法。这些共轭物在治疗中很有用。
• Antileukotrienic phenethylamido derivatives of arylalkanoic acids in the treatment of ulcerative colitis
  作者：Richard Junek、Miloslav Kverka、Antonín Jandera、Vladimíra Panajotová、Dalibor Šatinský、Miloš Macháček、Miroslav Kuchař

  DOI：10.1016/j.ejmech.2008.02.030

  日期：2009.1

  connecting chain between aromatic ring and carboxyl did not bring about the important improvement of this activity in comparison with previous derivatives of arylacetic acids. Possible relation between LTB4 biosynthesis inhibition and ulcerative colitis is seriously broken by the compound 8a with carbonyl as the additional functional group on the connecting chain between carboxyl and aromatic ring.

  制备了一系列带有甲基（苯乙基）氨基的芳基链烷酸衍生物，并评估了它们对LTB 4生物合成的抑制作用。回归分析表明，该活性对α-甲基和α-未取代的链烷酸衍生物的亲脂性的抛物线依赖性略有不同。由α-未取代的链烷酸得到的关系被先前制备的类似的芳族丙烯酸衍生物组所扩展，而回归系数和统计标准没有任何变化。结论是，活性最高的化合物属于2-芳基丙酸衍生物，其亲脂性接近log  P opt（= 6.97）。但一般而言，与先前制备的一系列衍生物IV相比，所研究化合物酸性部分的结构变化并未产生LTB 4生物合成抑制作用的实质性改善。在三种炎症动物模型中评估了所研究化合物的抗炎作用，并跟踪了它们在溃疡性结肠炎（UC）治疗中的可能用途。从12种评估的化合物中，有4种化合物比标准的柳氮磺胺吡啶在UC抑制中的活性更高，但是可以说，与以前的芳环酸酯衍生物相比，芳环和羧基之间的连接链的变化并没有显着改善该活性。酸。LTB之
• Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
  作者：Guoxia Ji、Qinghua Guo、Qidi Xue、Ruifang Kong、Shiben Wang、Kang Lei、Renmin Liu、Xuekun Wang

  DOI：10.3390/molecules26226907

  日期：——

  GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM.

  GPR120是治疗2型糖尿病（T2DM）的一个有前途的靶点，它被游离脂肪酸（FFAs）激活，并刺激胰高血糖素样肽-1（GLP-1）的释放。GLP-1作为一种胃肠激素，可以增强胰岛β细胞对葡萄糖依赖的胰岛素分泌，并降低血糖。在这项研究中，设计和合成了一系列新型GPR120激动剂，以改善苯丙酸GPR120激动剂TUG-891的稳定性和亲水性。化合物11b表现出优异的GPR120激动活性和药代动力学特性，并且能够以剂量依赖的方式降低正常小鼠的血糖。此外，即使在100 mg/kg的剂量下也没有观察到低血糖的副作用。此外，11b在饮食诱导性肥胖（DIO）小鼠中显示出良好的抗高血糖作用。分子模拟表明，化合物11b可以进入GPR120的活性位点并与ARG99发生相互作用。综合这些结果，表明化合物11b可能是治疗T2DM的有前途的药物候选物。
• [EN] SUBSTITUTED 4-HYDROXY-PHENYLALCANOIC ACID DERIVATIVES WITH AGONIST ACTIVITY TO PPAR-GAMMA<br/>[FR] DERIVES D'ACIDE 4-HYDROXY-PHENYLALCANOIQUE SUBSTITUE POSSEDANT UNE ACTIVITE AGONISTE ENVERS PPAR-GAMMA
  申请人：GLAXO GROUP LIMITED

  公开号：WO1997031907A1

  公开（公告）日：1997-09-04

  (EN) A compound having formula (I), wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C1-6alkyl, C1-3alkoxy, C1-3fluoroalkoxy, nitrile, or -NR7R8 where R7 and R8 are independently hydrogen or C1-3alkyl; (ii) a 5- or 6-membered heterocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring (a), wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C1-6alkylene; (v) -MC1-6alkylene or C1-6alkyleneMC1-6alkylene, wherein M is O, S, or -NR2 wherein R2 represents hydrogen or C1-3 alkyl; (vi) a 5- or 6-membered heterocyclic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by C1-3 alkyl; and (vii) Het-C1-6alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C1-3alkylene; R1 represents hydrogen or C1-3alkyl; Z is selected from the group consisting of: (viii) -(C1-3alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) -NR3R4, wherein R3 represents hydrogen or C1-3alkyl, and R4 represents -Y-(C=O)-T-R5, or -Y-(CH(OH))-T-R5.(FR) Cette invention concerne un composé correspondant à la formule (I) où A est choisi dans le groupe comprenant les éléments suivants: (i) un phényle éventuellement substitué par un ou plusieurs atomes halogènes, alkyle C1-6, alcoxy C1-3, fluoroalcoxy C1-3, nitrile ou -NR7R8, R7 et R8 représentant indépendamment hydrogène ou alkyle C1-3; (ii) un groupe hétérocyclique à 5 ou 6 branches contenant un ou plusieurs hétéroatomes choisis parmi oxygène, azote et soufre; et (iii) un anneau (a) bicyclique fusionné dans lequel l'anneau C représente un groupe hétérocyclique tel que défini dans le point (ii) susmentionné, cet anneau bicyclique étant attaché au groupe B par un des atomes de l'anneau C. B est choisi dans le groupe comprenant les éléments suivants: (iv) alcylène C1-6; (v) -MC1-6alcylène ou C1-6alcylèneMC1-6alcylène où M représente O, S ou NR2, R2 représentant hydrogène ou alkyle C1-3; (vi) un groupe hétérocyclique à 5 ou 6 branches contenant au moins un hétéroatome d'azote et, éventuellement, un ou plusieurs autres hétéroatomes choisis parmi oxygène, azote et soufre, ledit groupe étant éventuellement substitué par alkyle C1-3; et (vii) Het-C1-6alcylène où Het représente un groupe hétérocyclique tel que défini dans le point (vi) susmentionné. Alk représente alcylène C1-3, tandis que R1 représente hydrogène ou alkyle C1-3, et que Z est choisi dans le groupe comprenant les éléments suivants: (viii) -(C1-3alcylène)phényle, lequel phényle est éventuellement substitué par un ou plusieurs atomes halogènes; et enfin (ix) -NR3R4 où R3 représente hydrogène ou alkyle C1-3, et R4 représente -Y-(C=O)-T-R5 ou -Y-(CH(OH))-T-R5.

  化合物的化学式为(I)，其中A选自以下组中的一种：(i)苯基，其中所述苯基可以选用一个或多个卤素原子，C1-6烷基，C1-3烷氧基，C1-3氟烷氧基，腈或-NR7R8，其中R7和R8独立地表示氢或C1-3烷基；(ii)含有至少一个氧、氮或硫杂原子的5-或6-成员杂环基；以及(iii)融合的双环环(a)，其中环C代表上述(ii)中定义的杂环基，该双环环通过环C的一个环原子连接到基团B上；B选自以下组中的一种：(iv)C1-6烷基；(v)-MC1-6烷基或C1-6烷基MC1-6烷基，其中M为O、S或-NR2，而R2表示氢或C1-3烷基；(vi)含有至少一个氮杂原子的5-或6-成员杂环基，且可选地含有至少一个来自氧、氮或硫的进一步杂原子，并可选地被C1-3烷基取代；以及(vii)Het-C1-6烷基，其中Het代表上述(vi)中定义的杂环基；Alk表示C1-3烷基；R1表示氢或C1-3烷基；Z选自以下组中的一种：(viii) -(C1-3烷基)苯基，所述苯基可以选用一个或多个卤素原子；以及(ix) -NR3R4，其中R3表示氢或C1-3烷基，而R4表示-Y-(C=O)-T-R5或-Y-(CH(OH))-T-R5。
• Intermediate compound which is used for the preparation of pioglitazone
  申请人：Lopez Duran Ernesto

  公开号：US20070083050A1

  公开（公告）日：2007-04-12

  The present invention relates to a novel compound of formula (IV) which is an intermediate that can be used for the preparation of pioglitazone. It also relates to a method of obtaining the novel compound (IV) starting from the natural product L-tyrosine, in which the amino group is protected in the form of aromatic imino group, and a method of obtaining pioglitazone from the said intermediate.

  本发明涉及一种新的化合物，其化学式为(IV)，该化合物是一种中间体，可用于制备吡格列酮。本发明还涉及一种从天然产物L-酪氨酸开始，将氨基保护成芳香亚胺基，得到上述新化合物(IV)的方法，以及从该中间体得到吡格列酮的方法。