2,5-diphenyloxazole-4-carboxylic acid | 18735-78-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2,5-diphenyloxazole-4-carboxylic acid
• 英文别名: 2,5-Diphenyl-oxazol-4-carbonsaeure；Diphenyl-1,3-oxazole-4-carboxylic acid；2,5-diphenyl-1,3-oxazole-4-carboxylic acid
• CAS: 18735-78-9
• 化学式: C₁₆H₁₁NO₃
• mdl: MFCD09812894
• 分子量: 265.268
• InChiKey: YKZSHSBBYKLXNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,5-diphenyloxazole-4-carboxylic acid 在 溶剂黄146 、 silver carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以100%的产率得到2,5-二苯基恶唑
  参考文献：
  名称：

  Pd(ii)-catalyzed direct C5-arylation of azole-4-carboxylates through double C–H bond cleavage

  摘要：

  首次实现了通过双C–H键断裂的铂催化直接C5-芳基化反应，将简单的未活化芳烃与azole-4-羧酸酯进行反应。该协议提供了一种简便的方法，获得了多种5-芳基取代的azole-4-羧酸衍生物，并具有良好的功能团耐受性。

  DOI：

  10.1039/c2cc00081d
• 作为产物：
  描述：

  ethyl 2,5-diphenyloxazole-4-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以97%的产率得到2,5-diphenyloxazole-4-carboxylic acid
  参考文献：
  名称：

  2-氯恶唑-4-羧酸乙酯：一种通用的中间体，用于合成取代的恶唑。

  摘要：

  [反应：见正文]通过一系列区域控制的卤化反应和钯催化的偶联反应，由2-氯恶唑-4-羧酸乙酯（2）合成了各种取代的恶唑。该方法学应用于一系列2,4-二取代，2,5-二取代和2,4,5-三取代的恶唑的合成。

  DOI：

  10.1021/ol0262800

文献信息

• Inhibitors of P2X3
  申请人：Brotherton-Pleiss E. Christine

  公开号：US20070037974A1

  公开（公告）日：2007-02-15

  Compounds of formula 1 are modulators of P2X3 useful for the treatment of pain and genito-urinary, gastrointestinal, and respiratory disorders: wherein R 1 is —C(═S)CH 3 , pyridyl, pyrimidinyl, pyrazinyl, thiazolyl, furyl, furylcarbonyl, acetyl, or carbamoyl; R 2a and R 2b are independently H, methyl, or ethyl; R 3 is H or methyl; Y is a bond, —(CR 4 R 5 ) n — or —CR 4 ═CR 5 —; wherein R 4 and R 5 are each independently H or methyl and n is 1 or 2; X is N or CH; A is phenyl, 5-membered heterocyclyl, or 6-membered heterocyclyl; R 6 , R 7 and R 8 are each independently H, halo, lower alkyl, cycloalkyl, alkylthio, alkylthio-lower alkyl, alkylsulfonyl-lower alkyl, di(lower alkyl)amino-lower alkyl, morpholinyl-lower alkyl, 4-methyl-piperazinyl-methyl, trifluoromethyl, pyridyl, tetrazolyl, thiophenyl, phenyl, biphenyl, or benzyl (where thiophenyl, phenyl and benzyl are substituted with 0-3 lower alkyl, halo, sulfonamido, trifluoromethyl, lower alkoxy or lower alkylthio) or R 6 and R 7 together form a 5-membered or 6-membered carbocyclic or heterocyclic ring substituted with 0-3 substituents selected from the group consisting of lower alkyl, lower alkoxy, oxo, halo, thiophenyl-lower alkyl, phenyl, benzyl (where phenyl and benzyl are substituted with 0-3 lower alkyl, halo, sulfonamido, trifluoro-methyl, lower alkoxy, lower alkylthio, amino-lower alkyl, lower alkylamino-lower alkyl, or di(lower alkyl)amino-lower alkyl); and pharmaceutically acceptable salts thereof; wherein when R 1 is pyrimidin-2-yl, X is N, Y is a bond and A is oxazol-5-yl the carbon atom at position 4 in said oxazol-5-yl is not substituted by propyl when the carbon atom at position 2 in said oxazol-5-yl is substituted by substituted phenyl and the carbon atom at position 4 in said oxazol-5-yl is not substituted by phenyl when the carbon atom at position 2 is substituted by unsubstituted or substituted phenyl.

  式1的化合物是P2X3的调节剂，用于治疗疼痛和泌尿生殖、胃肠和呼吸系统疾病： 其中 R 1 为—C(═S)CH 3 ，吡啶基，嘧啶基，吡嗪基，噻唑基，呋喃基，呋喃甲酰基，乙酰基或氨基甲酰基；R 2a 和R 2b 独立地为H，甲基或乙基；R 3 为H或甲基；Y为键，—(CR 4 R 5 ) n —或—CR 4 ═CR 5 —；其中R 4 和R 5 各自独立地为H或甲基，n为1或2；X为N或CH；A为苯基，5-成员杂环基或6-成员杂环基；R 6 ，R 7 和R 8 各自独立地为H，卤素，低碳基，环烷基，烷基硫醚，烷基硫醚-低碳基，烷基磺酰基-低碳基，二(低碳基)氨基-低碳基，吗啉基-低碳基，4-甲基哌嗪基-甲基，三氟甲基，吡啶基，四唑基，噻吩基，苯基，联苯基或苄基（其中噻吩基，苯基和苄基被0-3个低碳基，卤素，磺酰胺基，三氟甲基，低烷氧基或低烷硫基取代）或R 6 和R 7 一起形成一个被0-3个取自由低碳基，低烷氧基，氧代基，卤素，噻吩基-低碳基，苯基，苄基（其中苯基和苄基被0-3个低碳基，卤素，磺酰胺基，三氟甲基，低烷氧基，低烷硫基，氨基-低碳基，烷基氨基-低碳基或二(低碳基)氨基-低碳基取代）的5-成员或6-成员碳环或杂环取代环；及其药学上可接受的盐；其中当R 1 为嘧啶-2-基时，X为N，Y为键，A为噁唑-5-基时，所述噁唑-5-基中位置4的碳原子在所述噁唑-5-基中位置2的碳原子被取代的苯基取代时不被丙基取代，且所述噁唑-5-基中位置4的碳原子在位置2被取代的苯基取代时不被苯基取代。
• Identification of new Cdc25 dual specificity phosphatase inhibitors in a targeted small molecule array
  作者：Alexander P Ducruet、Robert L Rice、Kenji Tamura、Fumiaki Yokokawa、Shiho Yokokawa、Peter Wipf、John S Lazo

  DOI：10.1016/s0968-0896(00)00069-9

  日期：2000.6

  phosphatase inhibitors (Rice, R. L.; Rusnak, J. M.; Yokokawa, F.; Yokokawa, S.; Messner, D. J.; Boynton, A. L.; Wipf, P.; Lazo, J. S. Biochemistry 1997, 36, 15965). Several analogues were identified as effective inhibitors of the protein tyrosine phosphatase (PTPase) PTP1B and the DSPases VHR and Cdc25B2. Two compounds, FY3-alphaalpha09 and FY21-alphaalpha09, were partial competitive inhibitors of Cdc25B2

  双重特异性蛋白磷酸酶（DSPase）是信号转导，肿瘤发生和细胞周期的关键调节因子。然而，很少有有效的或特异性的DSPase抑制剂可用于这些药理靶标。我们已经使用了组合/平行合成的方法来硬化可变核心区域，并修改4-（苄基-（2- [2- [2,5-二苯基-恶唑-4-羰基）-氨基]-乙基）-氨基甲酰基的侧链）-2-癸酰氨基丁酸（或SC-alphaalphadelta9），它是先前描述的磷酸酶抑制剂文库（Rice，RL; Rusnak，JM; Yokokawa，F .; Yokokawa，S .; Messner，DJ）中最活跃的元素； Boynton，AL； Wipf，P。； Lazo，JS Biochemistry 1997，36，15965）。几种类似物被鉴定为蛋白酪氨酸磷酸酶（PTPase）PTP1B和DSPases VHR和Cdc25B2的有效抑制剂。FY3-alphaalpha09和
• The synthesis of some substituted 4-acetyl-oxazoles and the corresponding acids
  作者：A. W. Allan、B. H. Walter

  DOI：10.1039/j39680001397

  日期：——

  condensation of aromatic aldehydes with hydroxyimino-β-diketones in the presence of dry hydrogen chloride and reduction of the intermediate N-oxides. The acetyl-oxazoles were oxidised to the corresponding acids with sodium hypobromite.

  在干燥的氯化氢存在下，通过芳族醛与羟基亚氨基-β-二酮的缩合和中间体N-氧化物的还原，已经制备了几种乙酰基-恶唑。用次溴酸钠将乙酰基-恶唑氧化为相应的酸。
• Pfleger; v. Strandtmann, Chemische Berichte, 1957, vol. 90, p. 1455,1464
  作者：Pfleger、v. Strandtmann

  DOI：——

  日期：——
• Combinatorial synthesis and biological evaluation of Library of small-molecule Ser/Thr-protein phosphatase inhibitors
  作者：Peter Wipf、April Cunningham、Robert L. Rice、John S. Lazo

  DOI：10.1016/s0968-0896(96)00199-x

  日期：1997.1

  In eukaryotes, phosphorylation of serine, threonine, and tyrosine residues on proteins is a fundamental posttranslational regulatory process for such functions as signal transduction, gene transcription, RNA splicing, cellular adhesion, apoptosis, and cell cycle control. Based on functional groups present in natural product serine/threonine protein phosphatase (PSTPase) inhibitors, we have designed pharmacophore model 1 and demonstrated the feasibility of a combinatorial chemistry approach for the preparation of functional analogues of 1. preliminary biological testing of 18 structural variants of 1 has identified two compounds with growth inhibitory activity against cultured human breast cancer cells. In vitro inhibition of the PSTPase PP2A was demonstrated with compound 1d. Using flow cytometry we observed that compound If caused prominent inhibition in the G1 phase of the cell cycle. Thus, the combinatorial modifications of the minimal pharmacophore 1 can generate biologically interesting antiproliferative agents. Copyright (C) 1997 Elsevier Science Ltd.