2-{3-[4-(2-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione | 178672-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-{3-[4-(2-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione
• 英文别名: 3-[4-(2-fluorophenyl)piperazin-1-yl]-propylphthalimide；2-[3-[4-(2-Fluorophenyl)piperazin-1-yl]propyl]isoindole-1,3-dione
• CAS: 178672-13-4
• 化学式: C₂₁H₂₂FN₃O₂
• 分子量: 367.423
• InChiKey: SFIJMTZZDDSHED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{3-[4-(2-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione 在 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 10.0h， 生成 N-{3-[4-(2-fluorophenyl)piperazin-1-yl]propyl}thiophene-2-carboxamide
  参考文献：
  名称：

  一种交互式SAR方法，用于发现新的杂化硫杂探针，作为亲和力在亚纳摩尔范围内的D2样受体的配体。

  摘要：

  合成了一系列的[（苯基哌嗪基）烷基]-异吲哚-1,3-二酮衍生物，用作多巴胺能受体的探针。在该系列中，化合物6a对D4和D3受体的亲和力最高，Ki值在低纳摩尔范围内，D2 / D4-和D2 / D3-选择性指数分别为72和20。采用最优化回合，得到Ki（D4）值为0.62 nM的D4选择性配体噻吩-2-羧酰胺9a，其丁基类似物10a的Ki（D4）和Ki（D3）值为0.03和0.26 nM。对接实验揭示了独特的D4残基Arg186在操纵配体D4亚型受体选择性中的重要性。

  DOI：

  10.1002/cbdv.201300204
• 作为产物：
  描述：

  苯酐 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 48.25h， 生成 2-{3-[4-(2-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  一种交互式SAR方法，用于发现新的杂化硫杂探针，作为亲和力在亚纳摩尔范围内的D2样受体的配体。

  摘要：

  合成了一系列的[（苯基哌嗪基）烷基]-异吲哚-1,3-二酮衍生物，用作多巴胺能受体的探针。在该系列中，化合物6a对D4和D3受体的亲和力最高，Ki值在低纳摩尔范围内，D2 / D4-和D2 / D3-选择性指数分别为72和20。采用最优化回合，得到Ki（D4）值为0.62 nM的D4选择性配体噻吩-2-羧酰胺9a，其丁基类似物10a的Ki（D4）和Ki（D3）值为0.03和0.26 nM。对接实验揭示了独特的D4残基Arg186在操纵配体D4亚型受体选择性中的重要性。

  DOI：

  10.1002/cbdv.201300204

文献信息

• \x9b3-(4-phenylpiperazin-1-yl)propyl-amino, thio and oxy!-pyridine,
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05688795A1

  公开（公告）日：1997-11-18

  The present invention relates to novel .alpha..sub.1 -adrenoceptor antagonists of Formula I: ##STR1## in which: p is 0 or 1; t is 0, 1 or 2; X is O, S or NR.sup.6 (in which R.sup.6 is hydro or (C.sub.1-6)alkyl); Y and Z are independently CH or N; R.sup.1 is hydro, hydroxy, halo, nitro, amino, cyano, (C.sub.1-4)alkylthio, acetylamino, trifluoroacetylamino, methylsulfonylamino, (C.sub.1-6)alkyl, (C.sub.3-6)cycloalkyl, (C.sub.3-6)cycloalkyl (C.sub.1-4)alkyl, oxazol-2-yl, aryl, heteroaryl, aryl (C.sub.1-4)alkyl, heteroaryl (C.sub.1-4)alkyl, (C.sub.1-6)alkyloxy, (C.sub.3-6)cycloalkyloxy, (C.sub.3-6)cycloalkyl (C.sub.1-4)alkyloxy, 2-propynyloxy, aryloxy, heteroaryloxy, aryl (C.sub.1-4)alkyloxy or heteroaryl (C.sub.1-4)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms and aryl or heteroaryl is optionally substituted with one to two substituents independently selected from halo and cyano); R.sup.2 is hydro, hydroxy, halo, cyano, (C.sub.1-6)alkyl or (C.sub.1-6)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms); R.sup.3 is -C (O)R.sup.7 (wherein R.sup.7 is (C.sub.1-6)alkyl, (C.sub.3-6)cycloalkyl, di(C.sub.1-4)alkylamino, N-(C.sub.1-4)alkyl-N-(C.sub.1-4)alkyloxyamino, (C.sub.1-4)alkyl((C.sub.1-4)alkyloxy)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or piperazin-1-yl); R.sup.4 is halo, hydroxy, cyano, (C.sub.1-6)alkyl or (C.sub.1-6)alkyloxy; and R.sup.5 is (C.sub.1-6)alkyl; and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明涉及以下式I的新型α1-肾上腺素受体拮抗剂：##STR1## 其中：p为0或1；t为0, 1或2；X为O、S或NR.sup.6（其中R.sup.6为羟基或（C.sub.1-6）烷基）；Y和Z独立地为CH或N；R.sup.1为羟基、羟基、卤素、硝基、氨基、氰基、（C.sub.1-4）烷基硫基、乙酰氨基、三氟乙酰氨基、甲磺酰氨基、（C.sub.1-6）烷基、（C.sub.3-6）环烷基、（C.sub.3-6）环烷基（C.sub.1-4）烷基、噁唑-2-基、芳基、杂环芳基、芳基（C.sub.1-4）烷基、杂环芳基（C.sub.1-4）烷基、（C.sub.1-6）烷氧基、（C.sub.3-6）环烷氧基、（C.sub.3-6）环烷基（C.sub.1-4）烷氧基、2-丙炔氧基、芳氧基、杂环芳氧基、芳基（C.sub.1-4）烷氧基或杂环芳基（C.sub.1-4）烷氧基（其中烷基可选择性地用1至3个卤原子取代，芳基或杂环芳基可选择性地用1至2个独立选择的卤素和氰基取代）；R.sup.2为羟基、羟基、卤素、氰基、（C.sub.1-6）烷基或（C.sub.1-6）烷氧基（其中烷基可选择性地用1至3个卤原子取代）；R.sup.3为-C（O）R.sup.7（其中R.sup.7为（C.sub.1-6）烷基、（C.sub.3-6）环烷基、二（C.sub.1-4）烷基氨基、N-（C.sub.1-4）烷基-N-（C.sub.1-4）烷氧基氨基、（C.sub.1-4）烷基（（C.sub.1-4）烷氧基）氨基、吡咯烷-1-基、哌啶-1-基、吗啉-4-基或哌嗪-1-基）；R.sup.4为卤素、羟基、氰基、（C.sub.1-6）烷基或（C.sub.1-6）烷氧基；R.sup.5为（C.sub.1-6）烷基；以及其药学上可接受的盐和N-氧化物。
• Synthesis and evaluation of antiproliferative activity of novel quinazolin-4(3H)-one derivatives
  作者：Ramineni Venkatesh、Suresh Kasaboina、Sridhara Janardhan、Nishant Jain、Rajashaker Bantu、Lingaiah Nagarapu

  DOI：10.1007/s00044-016-1632-9

  日期：2016.9

  Two series of novel quinazolin-4(3H)-one derivatives (10a–g and 11a–g) have been synthesized and evaluated for their in vitro antiproliferative activity against human HeLa, MIAPACA, MDA-MB-231, and IMR-31 cancer cell lines. The synthesized compounds were characterized by spectral (Fourier transform infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, high-resolution mass spectra)

  合成了两个系列的新型喹唑啉-4（3 H）-一衍生物（10a–g和11a–g），并评估了它们对人HeLa，MIAAPACA，MDA-MB-231和IMR-31的体外抗增殖活性癌细胞系。合成的化合物通过光谱（傅立叶红外光谱，1 H核磁共振，13 C核磁共振，高分辨率质谱）进行表征。其中，化合物11e和11g对MIAPACA人癌细胞系显示出强大的体外抗增殖活性，GI 50值为0.02，小于0.01μM。明显地，化合物10a，10b，10c，10g，11b，11c，11d，11e，11f显示了针对人癌细胞系MIAPACA，MDA-MB-231和IMR-31的GI 50值为0.1至0.87μM的活性。我们已经探索了HDAC8和EHMT2蛋白中可能的结合模式和关键的活性位点相互作用。对接结果是对实验结果的补充。
• Synthesis and biological evaluation of 2-fluoro and 3-trifluoromethyl-phenyl-piperazinylalkyl derivatives of 1<i>H</i>-imidazo[2,1-<i>f</i>]purine-2,4(3<i>H</i>,8<i>H</i>)-dione as potential antidepressant agents
  作者：Agnieszka Zagórska、Adam Bucki、Marcin Kołaczkowski、Agata Siwek、Monika Głuch-Lutwin、Gabriela Starowicz、Grzegorz Kazek、Anna Partyka、Anna Wesołowska、Karolina Słoczyńska、Elżbieta Pękala、Maciej Pawłowski

  DOI：10.1080/14756366.2016.1198902

  日期：2016.11.3

  2-fluoro and 3-trifluoromethylphenylpiperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (4-21) were synthesized and evaluated for their serotonin (5-HT1A/5-HT7) receptor affinity and phosphodiesterase (PDE4B and PDE10A) inhibitor activity. The study enabled the identification of potent 5-HT1A, 5-HT7 and mixed 5-HT1A/5-HT7 receptor ligands with weak inhibitory potencies for PDE4B and PDE10A

  合成了一系列的1H-咪唑并[2,1-f]嘌呤-2,4（3H，8H）-二酮（4-21）的2-氟和3-三氟甲基苯基哌嗪基烷基衍生物，并对其5-羟色胺（5-HT1A）进行了评估/ 5-HT7）受体亲和力和磷酸二酯酶（PDE4B和PDE10A）抑制剂的活性。该研究能够鉴定出对PDE4B和PDE10A具有弱抑制能力的有效5-HT1A，5-HT7和混合的5-HT1A / 5-HT7受体配体。已经使用胶束电动色谱（MEKC）系统和人肝微粒体（HLM）模型确定了亲脂性和代谢稳定性，从而完成了测试。在体内初步药理研究中，选择化合物8-（5-（4-（2-氟苯基）哌嗪-1-基）戊基）-1,3,7-三甲基-1H-咪唑并[2,1-f]嘌呤-2,4（3H，8H）-二酮（9）在小鼠的强迫游泳试验（FST）中表现为潜在的抗抑郁药。此外，由9引起的抗焦虑作用（2.5 mg / kg）要大于参考抗焦虑药地西epa。分子建模表明，1H-咪唑并[2
• 3-(4-phenylpiperazin-1-yl)propyl-amino, thio and oxy -pyridine, pyrimidine and benzene derivatives as alpha1-adrenoceptor antagonists
  申请人：F. Hoffmann-La Roche AG

  公开号：EP0711757A1

  公开（公告）日：1996-05-15

  The present invention relates to novel α₁-adrenoceptor antagonists of Formula I: in which: p is 0 or 1; t is 0, 1 or 2; X is O, S or NR⁶ (in which R⁶ is hydro or (C₁₋₆)alkyl); Y and Z are independently CH or N; R¹ is hydro, hydroxy, halo, nitro, amino, cyano, (C₁₋₄)alkylthio, acetylamino, trifluoroacetylamino, methylsulfonylamino, (C₁₋₆)alkyl, (C₃₋₆)cycloalkyl, (C₃₋₆)cycloalkyl(C₁₋₄)alkyl, oxazol-2-yl, aryl, heteroaryl, aryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkyl, (C₁₋₆)alkyloxy, (C₃₋₆)cycloalkyloxy, (C₃₋₆)cycloalkyl(C₁₋₄)alkyloxy, 2-propynyloxy, aryloxy, heteroaryloxy, aryl(C₁₋₄)alkyloxy or heteroaryl(C₁₋₄)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms and aryl or heteroaryl is optionally substituted with one to two substituents independently selected from halo and cyano); R² is hydro, hydroxy, halo, cyano, (C₁₋₆)alkyl or (C₁₋₆)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms); R³ is -C(O)R⁷ (wherein R⁷ is (C₁₋₆)alkyl, (C₃₋₆)cycloalkyl, di(C₁₋₄)alkylamino, N-(C₁₋₄)alkyl-N-(C₁₋₄)alkyloxyamino, (C₁₋₄)alkyl((C₁₋₄)alkyloxy)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or piperazin-1-yl); R⁴ is halo, hydroxy, cyano, (C₁₋₆)alkyl or (C₁₋₆)alkyloxy; and R⁵ is (C₁₋₆)alkyl; and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明涉及式 I 的新型 α₁-肾上腺素受体拮抗剂： 其中 p 是 0 或 1； t 是 0、1 或 2 X 是 O、S 或 NR⁶（其中 R⁶ 是氢或 (C₁₋₆)烷基）； Y 和 Z 独立地为 CH 或 N； R¹是氢、羟基、卤代、硝基、氨基、氰基、(C₁₋₄)烷硫基、乙酰氨基、三氟乙酰氨基、甲磺酰氨基、(C₁₋₆)烷基、(C₃₋₆)环烷基、(C₃₋₆)环烷基(C₁₋₄)烷基、噁唑-2-基、芳基、杂芳基、芳基(C₁₋₄)烷基、杂芳基(C₁₋₄)烷基、(C₁₋₆)烷氧基、(C₃₋₆)环烷氧基、(C₃₋₆)环烷基(C₁₋₄)烷氧基，2-丙炔氧基，芳基氧基，杂芳基氧基、芳基（C₁₋₄）烷氧基或杂芳基（C₁₋₄）烷氧基（其中烷基任选被一至三个卤原子取代，芳基或杂芳基任选被一至两个独立选自卤素和氰基的取代基取代）； R² 是氢、羟基、卤代、氰基、(C₁₋₆)烷基或(C₁₋₆)烷氧基（其中烷基任选被一至三个卤原子取代）； R³ 是 -C(O)R⁷（其中 R⁷ 是 (C₁₋₆)烷基、(C₃₋₆)环烷基、二(C₁₋₄)烷基氨基、N-(C₁₋₄)烷基-N-(C₁₋₄)烷氧基氨基、(C₁₋₄)烷基((C₁₋₄烷氧基)氨基、吡咯烷-1-基、哌啶-1-基、吗啉-4-基或哌嗪-1-基)； R⁴ 是卤素、羟基、氰基、(C₁₋₆)烷基或 (C₁₋₆)烷氧基；和 R⁵ 是 (C₁₋₆)烷基；及其药学上可接受的盐和 N-氧化物。
• Synthesis and biological evaluation of oxazole derivatives as T-type calcium channel blockers
  作者：Jie Eun Lee、Hun Yeong Koh、Seon Hee Seo、Yi Yeon Baek、Hyewhon Rhim、Yong Seo Cho、Hyunah Choo、Ae Nim Pae

  DOI：10.1016/j.bmcl.2010.05.030

  日期：2010.7

  T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pain. In this study, as a part of our ongoing efforts to develop potent T-type calcium channel blockers, we designed oxazole derivatives substituted with arylpiperazinylalkylamines. The oxazoles were synthesized in a convenient convergent synthetic method, and biologically evaluated against alpha(1G) (Ca(V)3.1) T-type calcium channel. Among total 41 oxazole compounds synthesized, the most active one was the compound 10-35 with an IC(50) value of 0.65 mu M, which is comparable with that of mibefradil. (C) 2010 Elsevier Ltd. All rights reserved.