1-(2-hydroxyethyl)-3-phenyl-5-methylpyrazole | 196810-78-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-hydroxyethyl)-3-phenyl-5-methylpyrazole
• 英文别名: 2-(5-methyl-3-phenyl-1H-pyrazol-1-yl)ethanol；2-(5-methyl-3-phenylpyrazol-1-yl)ethanol；2-(5-methyl-3-phenyl-pyrazol-1-yl)-ethanol
• CAS: 196810-78-3
• 化学式: C₁₂H₁₄N₂O
• mdl: MFCD27946885
• 分子量: 202.256
• InChiKey: WSUWPFKLFSRXNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：

  1-(2-hydroxyethyl)-3-phenyl-5-methylpyrazole 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-(5-methyl-3-phenyl-pyrazol-1-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：

  碳酸乙烯酯 、 3-甲基-5-苯基-1H-吡唑 在 sodium hydride 、 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 、 水 为溶剂， 反应 20.3h， 以59.6%的产率得到1-(2-hydroxyethyl)-3-phenyl-5-methylpyrazole
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AS MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS, USEFUL FOR THE TREATMENT AND/OR PREVENTION OF DISORDERS MODULATED BY A PPAR
  [FR] COMPOSES HETEROCYCLIQUES UTILISES COMME MODULATEURS DES RECEPTEURS ACTIVES PROLIFERATEURS DU PEROXYSOME (PPAR), UTILES DANS LE TRAITEMENT ET/OU LA PREVENTION DE TROUBLES MODULES PAR UN PPAR

  摘要：

  本发明涉及一种式(I)的化合物，或其药学上可接受的盐、溶剂合物、水合物或立体异构体，该化合物在治疗或预防由过氧化物酶体增殖激活受体（PPAR）介导的疾病中具有用途，如X综合征、2型糖尿病、高血糖、高脂血症、肥胖、凝血障碍、高血压、动脉硬化以及与X综合征和心血管疾病相关的其他疾病。

  公开号：

  WO2005051945A1

文献信息

• Small Molecule Library Synthesis Using Segmented Flow
  作者：Christina M. Thompson、Jennifer L. Poole、Jeffrey L. Cross、Irini Akritopoulou-Zanze、Stevan W. Djuric

  DOI：10.3390/molecules16119161

  日期：——

  Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing libraries. The reactions were performed on a 0.2 mmol scale, enabling tens of milligrams of material to be generated in a single 200 mL reaction plug. The methodology allowed library synthesis in half the time of conventional microwave synthesis while maintaining similar yields. The ability to perform multiple, potentially unrelated reactions in a single run is ideal for making small quantities of many different compounds quickly and efficiently.

  流动化学作为一种简便、高效且安全的合成技术，已获得广泛认可，适用于多种有机和无机分子的制备，其规模从复杂的大型天然产物到硅纳米颗粒不等。本文介绍了一种利用流动化学合成化合物库的方法，该方法采用氟烃不溶性溶剂作为反应间的间隔物。我们在合成两个含小杂环的化合物库中验证了该方法。反应规模为0.2毫摩尔，单次200毫升反应插件即可生成数十毫克的物质。与传统微波合成相比，该方法在保持相似产率的同时，将化合物库合成时间缩短了一半。能够在单次运行中进行多个潜在不相关的反应，这为快速高效地制备少量多种不同化合物提供了理想条件。
• Palladium(II) and platinum(II) complexes with N1-hydroxyethyl-3,5-pyrazole derived ligands
  作者：José A. Perez、Vanessa Montoya、José A. Ayllon、Mercè Font-Bardia、Teresa Calvet、Josefina Pons

  DOI：10.1016/j.ica.2012.07.027

  日期：2013.1

  Abstract Reaction of the ligands 2-(5-methyl-3-phenyl-1 H -pyrazol-1-yl)ethanol ( L1 ) and 2-(3-methyl-5-phenyl-1 H -pyrazol-1-yl)ethanol ( L2 ) with [MCl 2 (CH 3 CN) 2 ] (M = Pd(II), Pt(II)) gave the complexes trans -[MCl 2 L 2 ] (M = Pd(II) and Pt(II), L = L1 , L2 ). The new complexes were characterised by elemental analyses, conductivity measurements, mass spectrometry, IR, 1 H and 13 C 1 H} NMR

  摘要配体2-（5-甲基-3-苯基-1 H-吡唑-1-基）乙醇（L1）与2-（3-甲基-5-苯基-1 H-吡唑-1-基）的反应乙醇（L2）与[MCl 2（CH 3 CN）2]（M = Pd（II），Pt（II））得到反式-[MCl 2 L 2]（M = Pd（II）和Pt（II）的配合物），L = L1，L2）。通过元素分析，电导率测量，质谱，IR，1 H和13 C 1 H} NMR光谱对新配合物进行表征。通过X射线衍射解析了配体L2和反式-[PdCl 2 L 2]（L ＝ L1，L2）的配合物的晶体和分子结构。两种钯配合物均由单体反式-[PdCl 2 L 2]（L = L1，L2）组成，分子堆积通过分子间氢键相互作用确定。络合物[PdCl 2 L 2]（L = L1，L2）在CDCl 3溶液中的NMR光谱，这与吡唑配体绕Pd–N键的旋转非常慢是一致的，因此可以在溶液中观察到两个构象异构体（顺式和反式）。对于复合物[PtCl
• Substituted tridentate pyrazolyl ligands for chromium and nickel-catalyzed ethylene oligomerization reactions: effect of auxiliary ligand on activity and selectivity
  作者：Lucilene L. de Oliveira、Roberta R. Campedelli、Adão L. Bergamo、Ana H. D. P dos Santos、Osvaldo L. Casagrande

  DOI：10.1590/s0103-50532010000700019

  日期：——

  Two new chromium(III) complexes [CrCl3(L)] based on tridentate ligands (1a, L = bis[2-(3-phenyl-1-pyrazolyl)ethyl)]amine; 2a, L = bis[2-(3-methyl-5-phenyl-l-pyrazolyl)ethyl]sulfide) have been prepared and characterized by elemental analysis. Upon activation with methylaluminoxane (MAO), these pre-catalysts showed high turnover frequencies for ethylene oligomerization under optimized conditions (TOFs = 22.9-36.4×10³ mol C2H4 (mol CrIII)-1 h-1, [Cr] = 10.0 µmol, 80 ºC, 20 bar ethylene, MAO: Cr = 300, oligomerization time = 20 min), producing α-olefins in the range C4-C14+ with high selectively (67.71-73.47%). The catalytic performances are substantially affected by the ligand environment, especially the substituents at the 3- and 5-positions of the pyrazolyl rings. In parallel, the use of nickel complexes such as NiCl2bis[2-(3,5-dimethyl-1-pyrazolyl)methyl]benzylamine} (3) and NiCl2bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl)]ether} (5) in oligomerization reactions carried out in the presence of triphenylphosphine (PPh3) afforded highly active catalytic systems with turnover frequencies (TOFs) varying from 36.4 to 154.2×10³ mol C2H4 (mol NiII)-1 h-1. The presence of this auxiliary ligand has a strong impact on the selectivity towards the production of α-olefins, decreasing substantially the amount of 1-butene with a concominat increase of the 2-butene fractions. Attempts to crystallize the nickel complex 3 afforded the tetrametallic [(L)(µ3-Cl)NiCl}4] (4, L = 1-anilinomethyl-3,5-dimethylpyrazole) which was characterized by X-ray diffraction analysis.

  两种基于三齿配体的新型铬(III)络合物[CrCl3(L)] (1a, L = 双[2-(3-苯基-1-吡唑基)乙基)]胺； 2a，L=双[2-(3-甲基-5-苯基-1-吡唑基)乙基]硫醚)已被制备并通过元素分析进行​​表征。用甲基铝氧烷 (MAO) 活化后，这些预催化剂在优化条件下表现出乙烯低聚的高周转频率 (TOF = 22.9-36.4×10³ mol C2H4 (mol CrIII)-1 h-1, [Cr] = 10.0 µmol, 80 ℃，20 bar 乙烯，MAO：Cr = 300，低聚时间 = 20 分钟），以高选择性 (67.71-73.47%) 生产 C4-C14+ 范围内的 α-烯烃。催化性能很大程度上受到配体环境的影响，特别是吡唑环3-和5-位的取代基。同时，使用镍络合物，例如 NiCl2双[2-(3,5-二甲基-1-吡唑基)甲基]苄胺} (3) 和 NiCl2双[2-(3,5-二甲基-1-)吡唑基)乙基)]醚} (5) 在三苯基膦 (PPh3) 存在下进行的低聚反应中提供了高活性催化体系，其周转频率 (TOF) 从 36.4 到 154.2×10³ mol C2H4 (mol NiII)-1 h -1。这种辅助配体的存在对α-烯烃生产的选择性有很大的影响，显着减少了1-丁烯的量，同时增加了2-丁烯的馏分。尝试结晶镍络合物 3 得到四金属 [(L)(μ3-Cl)NiCl}4] (4, L = 1-苯胺基甲基-3,5-二甲基吡唑)，通过 X 射线衍射分析对其进行表征。
• [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。