2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethanol | 196810-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethanol
• 英文别名: 2-(1-methyl-4-phenylimidazol-2-yl)ethanol
• CAS: 196810-82-9
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: ORTOIUYGGQSINR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethanol 在 lithium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 26.5h， 生成 2S-(2-benzoyl-phenylamino)-3-{4-[2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-ethoxy]-phenyl}-propionic acid
  参考文献：
  名称：

  N-(2-Benzoylphenyl)-l-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety

  摘要：

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-{2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.

  DOI：

  10.1021/jm980413z
• 作为产物：
  描述：

  4-苯基咪唑 在 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethanol
  参考文献：
  名称：

  [EN] TRIAZOLOPYRIDINONE PDE10 INHIBITORS
  [FR] INHIBITEURS DE PDE10 DE TRIAZOLOPYRIDINONE

  摘要：

  本发明涉及三唑吡啶酮化合物，可用作治疗与磷酸二酯酶10（PDE10）相关的中枢神经系统疾病的治疗剂。本发明还涉及利用这些化合物治疗神经系统和精神障碍，如精神分裂症、精神病或亨廷顿病，以及与纹状体功能不足或基底神经节功能障碍相关的疾病。

  公开号：

  WO2013074390A1

文献信息

• [EN] TRIAZOLO- AND PYRAZOLOQUINAZOLINE DERIVATIVES AS PDE10A ENZYME INHIBITOR<br/>[FR] DÉRIVÉS DE TRIAZOLO- ET DE PYRAZOLOQUINAZOLINE EN TANT QU'INHIBITEURS D'ENZYME PDE10A
  申请人：LUNDBECK & CO AS H

  公开号：WO2012007006A1

  公开（公告）日：2012-01-19

  The invention relates to compounds of the formula (I) and their use as pharmaceutical ingredients, in particular for the treatment of CNS related diseases.

  本发明涉及式(I)化合物的用途，以及它们作为药物成分的应用，特别是用于治疗与中枢神经系统相关的疾病。
• [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。
• Modulators of peroxisome proliferator activated receptors (ppar)
  申请人：Gossett Stacy Lynn

  公开号：US20050075378A1

  公开（公告）日：2005-04-07

  The present invention is directed to a compound of formula I, and pharmaceutically acceptable salts, solvates, hydrates or stereoisomer thereof, which are useful in treating Syndrome X, Type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to Syndrome X as well as cardiovascular diseases.

  本发明涉及一种I式化合物，以及其药学上可接受的盐、溶剂、水合物或立体异构体，该化合物在治疗X综合征、2型糖尿病、高血糖、高脂血症、肥胖症、凝血障碍、高血压、动脉硬化以及与X综合征相关的其他疾病以及心血管疾病方面有用。
• Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to PPAR-gamma
  申请人：Glaxo Wellcome Inc.

  公开号：US06294580B1

  公开（公告）日：2001-09-25

  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 hetrocyclic 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 C1-3alkyl; (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 C1-3alkyl; 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.

  化合物的化学式为(I)，其中A被选择自以下组：(i)苯基，其中所述苯基可选地被一个或多个卤素原子，C1-6烷基，C1-3烷氧基，C1-3氟烷氧基，腈基或-NR7R8取代，其中R7和R8分别为氢或C1-3烷基；(ii)一个含有至少一个氧、氮或硫杂原子的5-或6-成员杂环基团；和(iii)融合的双环环(a)，其中环C代表如上(ii)中定义的杂环基团，所述双环环通过环C的一个环原子连接到基团B上；B被选择自以下组：(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，其中R2表示氢或C1-3烷基；(vi)一个含有至少一个氮杂原子的5-或6-成员杂环基团，可选地至少含有一个来自氧、氮和硫的进一步杂原子，并可选地被C1-3烷基取代；和(vii)Het-C1-6烷基，其中Het代表如上(vi)中定义的杂环基团；Alk代表C1-3烷基；R1代表氢或C1-3烷基；Z被选择自以下组：(viii) -（C1-3烷基）苯基，所述苯基可选地被一个或多个卤素原子取代；和(ix) -NR3R4，其中R3代表氢或C1-3烷基，R4代表—Y—（C═O）—T—R5或—Y—（CH(OH))—T—R5。
• MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS (PPAR)
  申请人：Gossett Lynn Stacy

  公开号：US20080167310A1

  公开（公告）日：2008-07-10

  The present invention is directed to a compound of formula I, and pharmaceutically acceptable salts, solvates, hydrates or stereoisomer thereof, which are useful in treating Syndrome X, Type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to Syndrome X as well as cardiovascular diseases.

  本发明涉及公式I的化合物及其药学上可接受的盐、溶剂化合物、水合物或立体异构体，其可用于治疗X综合症、II型糖尿病、高血糖、高血脂、肥胖症、凝血异常、高血压、动脉硬化以及与X综合症和心血管疾病有关的其他疾病。