(E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-acrylic acid | 73221-47-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-acrylic acid
• 英文别名: 1,3-Diphenyl-1h-pyrazole-4-acrylic acid；3-(1,3-diphenylpyrazol-4-yl)prop-2-enoic acid
• CAS: 73221-47-3
• 化学式: C₁₈H₁₄N₂O₂
• mdl: MFCD01957221
• 分子量: 290.321
• InChiKey: QWPUNBPIUCTWSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  (E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-acrylic acid 在 溴 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 (Z)-2-Bromo-3-(1,3-diphenyl-1H-pyrazol-4-yl)-acrylic acid
  参考文献：
  名称：

  4-Functionally-substituted 3-heterylpyrazoles: XVI. 3-(3-Arylpyrazol-4-yl)propyonic acids

  摘要：

  Bromination of 3-(3-arylpyrazol-4-yl)acrylic acids led to the formation of 2-bromo-3-(3-arylpyrazol-4yl)acrylic acids that were converted into 3-(3-arylpyrazol-4-yl)propynoic acids by treatment of potassium hydroxide with an alcoholic solution.

  DOI：

  10.1134/s1070428006050095
• 作为产物：
  描述：

  1,3-二苯-1H-吡唑-4-甲醛 在 哌啶 、 sodium hydroxide 作用下， 以 吡啶 、 甲醇 、 水 为溶剂， 反应 2.5h， 生成 (E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-acrylic acid
  参考文献：
  名称：

  Bernard; Hulley; Molenda, Pharmazie, 1986, vol. 41, # 8, p. 560 - 562

  摘要：

  DOI：

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。
• Synthesis and SAR studies of novel 1,2,4-oxadiazole-sulfonamide based compounds as potential anticancer agents for colorectal cancer therapy
  作者：Farheen Shamsi、Phool Hasan、Aarfa Queen、Afzal Hussain、Parvez Khan、Bushra Zeya、Hannah M. King、Sandeep Rana、Jered Garrison、Mohamed F. Alajmi、M. Moshahid Alam Rizvi、Muhammad Zahid、Md Imtaiyaz Hassan、Mohammad Abid

  DOI：10.1016/j.bioorg.2020.103754

  日期：2020.5

  diverse series of 1,2,4-oxadiazoles based substituted compounds were designed, synthesized and evaluated as anticancer agents targeting carbonic anhydrase IX (CAIX). Initial structure-activity analysis suggested that the thiazole/thiophene-sulfonamide conjugates of 1,2,4-oxadiazoles exhibited potent anticancer activities with low μM potencies. Compound OX12 exhibited antiproliferative activity (IC50 =

  设计，合成和评估了一系列基于1,2,4-恶二唑的取代化合物，并将其作为靶向碳酸酐酶IX（CAIX）的抗癌剂。初步的结构活性分析表明，1,2,4-恶二唑的噻唑/噻吩-磺酰胺共轭物显示出有效的抗癌活性，且μM效力低。化合物OX12表现出抗增殖活性（IC50 = 11.1 µM），并对与肿瘤相关的CAIX具有明显的抑制作用（IC50 = 4.23 µM）。因此，对OX12进行了结构优化，并合成并评估了其SAR定向衍生物（OX17-27）。通过这种迭代，化合物OX27的抗增殖作用几乎增加了两倍（IC50 = 6.0 µM），可与临床药物阿霉素相比，并且对CAIX的效力明显更高（IC50 = 0.74 µM）。另外，OX27处理降低了CAIX的表达，诱导了细胞凋亡和ROS的产生，抑制了结肠癌细胞的集落形成和迁移。我们的研究为进一步优化已鉴定的OX27提供了临床前理由，OX27是可能治疗CRC的合适先导。
• Unveiling novel diphenyl-1H-pyrazole based acrylates tethered to 1,2,3-triazole as promising apoptosis inducing cytotoxic and anti-inflammatory agents
  作者：Mohemmed Faraz Khan、Tarique Anwer、Afroz Bakht、Garima Verma、Wasim Akhtar、M. Mumtaz Alam、Moshahid Alam Rizvi、Mymoona Akhter、Mohammad Shaquiquzzaman

  DOI：10.1016/j.bioorg.2019.03.071

  日期：2019.6

  the apoptosis inducing potential of the compounds was determined by Hoechst staining and DNA fragmentation assay. Colony formation inhibition assay was also carried out to determine the long term cytotoxic potential of the molecules. Moreover, compounds 6e, 6f and 6n were also evaluated for anti-inflammatory activity by protein albumin denaturation assay and red blood cell membrane stabilizing assay

  微弱和次佳的治疗反应以及与现有抗癌治疗相关的副作用，已需要开发新的治疗方法来遏制该疾病。考虑到当前情况，按照多步反应方案合成了一系列1,2,3-三唑连接的3-（1,3-二苯基-1H-吡唑-4-基）丙烯酸酯。通过针对四类人癌细胞系MCF-7（乳腺），A549（肺）和HCT-116和HT-29（结肠）的体外磺基若丹明B试验，初步筛选抗癌潜能。经评估，几种化合物对所有细胞系均显示出有希望的生长抑制作用，特别是化合物6e，6f和6n。其中，化合物6f对A549，HCT-116，MCF-7和HT-29细胞系的IC50值分别为1.962、3.597、1.764和4.496 µM。此外，通过Hoechst染色和DNA片段化分析确定化合物的凋亡诱导潜力。还进行了菌落形成抑制试验以确定该分子的长期细胞毒性潜力。此外，还通过蛋白白蛋白变性测定法和红细胞膜稳定测定法评价了化合物6e，6f和6n的抗炎活性。
• [EN] NOVEL PYRAZOLE DERIVATIVES USEFUL AS POTASSIUM CHANNEL MODULATORS<br/>[FR] NOUVEAUX DÉRIVÉS DE PYRAZOLE UTILES COMME MODULATEURS DES CANAUX POTASSIQUES
  申请人：NEUROSEARCH AS

  公开号：WO2009003921A1

  公开（公告）日：2009-01-08

  This invention relates to novel pyrazole derivatives of formula (I) that are found to be potent modulators of potassium channels and, as such, are valuable candidates for the treatment of diseases or disorders as diverse as those which are responsive to the modulation of potassium channels.

  该发明涉及一种新型的嘧啶酮衍生物，其化学式为（I），发现其是钾通道的有效调节剂，因此是治疗对钾通道调节敏感的疾病或疾病的有价值候选药物。
• Synthesis of 3-(1, 3-Diphenyl-1<i>H</i>-pyrazol-4-yl) Propanoic Acids Using Diimide Reduction
  作者：M. Deepa、V. Harinadha Babu、R. Parameshwar、B. Madhava Reddy

  DOI：10.1155/2012/481682

  日期：——

  Pyrazole-1H-4-yl-acrylic acids (3a-j) were prepared from pyrazole-1H-4-carbaldehydes which in turn were prepared by the Vilsmeier-Haack reaction of phenyl hydrazone derivatives (1a-j). The reaction of pyrazole-1H-4-yl-acrylic acids to 3-(1, 3-diphenyl-1H-pyrazol-4-yl) propanoic acids (4a-j) was carried out using Pd-charcoal and diimide methods and % yields were compared. Though the yields may be slightly less in diimide method, the method was found to be economical, highly effective with simple operating procedure.

  从苯基腙衍生物（1a-j）的Vilsmeier-Haack反应制备的吡唑-1H-4-基丙烯酸（3a-j）制备而成的吡唑-1H-4-基丙烯酸（3a-j）制备自吡唑-1H-4-羰基醛。使用Pd-木炭和二亚甲基方法进行吡唑-1H-4-基丙烯酸反应制备3-(1,3-二苯基-1H-吡唑-4-基)丙酸（4a-j），并比较产率。尽管二亚甲基方法的产率可能略低，但该方法被证明在操作程序简单的情况下经济高效。