1-styrylpiperazine | 251369-16-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-styrylpiperazine
• 英文别名: 1-(2-Phenylethenyl)piperazine
• CAS: 251369-16-1
• 化学式: C₁₂H₁₆N₂
• 分子量: 188.272
• InChiKey: ZTPDAUHKSFYRGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-17-(2-chloropyridin-5-yl)androsta-5,16-diene 、 1-styrylpiperazine 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 15.0h， 生成
  参考文献：
  名称：

  N-substituted Piperazinopyridylsteroid Derivatives as Abiraterone Analogues Inhibit Growth and Induce Pro-apoptosis in Human Hormone-independent Prostate Cancer Cell Lines

  摘要：

  Nine new 17‐(piperazin‐1‐yl)pyridin‐5‐yl)steroids as abiraterone analogues were synthesized. Compounds 5d and 5g showed selective activities against 17α‐hydroxylase/C17,20‐lyase (CYP17A1) and aromatase (CYP19), respectively. IC50 values of 5d were 5.09 and >50 μm, whereas these values for 5g were >50 μm and 7.40 μm, respectively, for CYP17A1 and CYP19. Molecular modelling highlighted that the inhibitor designed to bind cytochrome P450 haem iron is a necessary condition but not the only rationale to explain inhibitory activity. These abiraterone analogues were then evaluated on hormone‐independent prostate cancer cell lines DU‐145 and PC‐3 and on hormone‐dependent breast and prostate cancer cell lines MCF‐7 and LNCaP, respectively. Compounds 5e, 5g and 5i have showed potent activities only on hormone‐independent prostate cancer cell lines DU‐145 and PC‐3 with 60–85% inhibition of both cell viability and growth at 10 nm with pro‐apoptotic mechanism as illustrated in PC‐3 cells by DNA ladder assay and Western blotting of Bax, Casp‐3 and its substrate, the poly (ADP–ribose) polymerase. We conclude that hybrid heterocycle steroids could be good lead compounds in the drug design especially against hormone‐independent prostate cancer.

  DOI：

  10.1111/cbdd.12195

文献信息

• A Nature-Inspired Design Yields a New Class of Steroids Against Trypanosomatids
  作者：Elena Aguilera、Cintya Perdomo、Alejandra Espindola、Ileana Corvo、Paula Faral-Tello、Carlos Robello、Elva Serna、Fátima Benítez、Rocío Riveros、Susana Torres、Ninfa I. Vera de Bilbao、Gloria Yaluff、Guzmán Alvarez

  DOI：10.3390/molecules24203800

  日期：——

  biological activity against Leishmania infantum, Leishmania amazonensis, and Trypanosoma cruzi in vitro and in vivo. We also assayed their genotoxicity and acute toxicity in vitro and in mice. The best compound, a steroidal thiosemicarbazone compound 8 (ID_1260) was active in vitro (IC50 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in Leishmania and T. cruzi. It also has low toxicity in vitro and

  恰加斯病和利什曼病是被世界卫生组织认定为公共卫生问题的地方性原生动物疾病。这些疾病影响着世界各地的数百万人，但目前还没有有效和低成本的治疗方法。从不同的生物体（蜱、植物、真菌）中分离出具有抗微生物和抗寄生虫活性的不同类固醇分子。这些分子具有复杂的结构，使得从头合成极其困难。在这项工作中，我们受天然类固醇的启发，设计了具有抗寄生虫潜力的新的更简单的化合物，并合成了一系列 19 种甾体亚芳基酮和噻唑烷肼。我们在体外和体内探索了它们对婴儿利什曼原虫、亚马逊利什曼原虫和克氏锥虫的生物活性。我们还在体外和小鼠中测定了它们的遗传毒性和急性毒性。最好的化合物，甾体缩氨基硫脲化合物 8 (ID_1260) 在体外 (IC50 200 nM) 和体内 (50 mg/kg 时感染减少 60%) 在利什曼原虫和克氏锥虫中均有活性。它还具有体外和体内低毒性（LD50 > 2000 mg/kg）和无遗传毒性作用，是一种有前景的抗锥虫药物开发化合物。
• Electrochemical Amidation: Benzoyl Hydrazine/Carbazate and Amine as Coupling Partners
  作者：Tipu Alam、Amitava Rakshit、Hirendra Nath Dhara、Angshuman Palai、Bhisma K. Patel

  DOI：10.1021/acs.orglett.2c02626

  日期：2022.9.16

  An electrochemical amidation of benzoyl hydrazine/carbazate and primary/secondary amine as coupling partners via concomitant cleavage and formation of C(sp2)–N bonds has been achieved. This methodology proceeds under metal-free and exogenous oxidant-free conditions producing N2 and H2 as byproducts. Mechanistic studies reveal the in situ generations of both acyl and N-centered radicals from benzoyl

  通过伴随的裂解和 C(sp 2 )-N 键的形成，实现了苯甲酰肼/咔巴酸酯和伯/仲胺作为偶联伙伴的电化学酰胺化。该方法在无金属和无外源氧化剂的条件下进行，产生 N 2和 H 2作为副产物。机理研究揭示了来自苯甲酰肼和胺的酰基和N中心自由基的原位生成。该协议的实用性通过大规模合成苯扎贝特（一种高脂血症药物）得到证明。
• Rapid parallel synthesis applied to the optimization of a series of potent nonpeptide neuropeptide Y-1 receptor antagonists
  作者：Miles G. Siegel、Michael O. Chaney、Robert F. Bruns、Michael P. Clay、Douglas A. Schober、Anne M. Van Abbema、Douglas W. Johnson、Buddy E. Cantrell、Patric J. Hahn、David C. Hunden、Donald R. Gehlert、Hamideh Zarrinmayeh、Paul L. Ornstein、Dennis M. Zimmerman、Gary A. Koppel

  DOI：10.1016/s0040-4020(99)00683-3

  日期：1999.9

  This study describes the integrated application of parallel synthesis and computational chemistry to the design of potent nonpeptide antagonists for the neuropeptide Y-1 (NPY1) receptor. A lead molecule was modeled in the active site of the NPY1 receptor, and a potentially fruitful region for analog construction was identified. Synthesis of suitable scaffolds followed by solution phase generation of a small library of analogs produced a compound with 5-fold improvement in binding over the already potent lead. This new compound was shown to be an unanticipated side product of the parallel synthesis reaction. (C) 1999 Elsevier Science Ltd. All rights reserved.
• N-substituted Piperazinopyridylsteroid Derivatives as Abiraterone Analogues Inhibit Growth and Induce Pro-apoptosis in Human Hormone-independent Prostate Cancer Cell Lines
  作者：Dominique Brossard、Ying Zhang、Shozeb M. Haider、Miriam Sgobba、Mohamed Khalid、Rémi Legay、Martine Duterque-Coquillaud、Philippe Galera、Sylvain Rault、Patrick Dallemagne、Safa Moslemi、Laïla El Kihel

  DOI：10.1111/cbdd.12195

  日期：2013.11

  Nine new 17‐(piperazin‐1‐yl)pyridin‐5‐yl)steroids as abiraterone analogues were synthesized. Compounds 5d and 5g showed selective activities against 17α‐hydroxylase/C17,20‐lyase (CYP17A1) and aromatase (CYP19), respectively. IC50 values of 5d were 5.09 and >50 μm, whereas these values for 5g were >50 μm and 7.40 μm, respectively, for CYP17A1 and CYP19. Molecular modelling highlighted that the inhibitor designed to bind cytochrome P450 haem iron is a necessary condition but not the only rationale to explain inhibitory activity. These abiraterone analogues were then evaluated on hormone‐independent prostate cancer cell lines DU‐145 and PC‐3 and on hormone‐dependent breast and prostate cancer cell lines MCF‐7 and LNCaP, respectively. Compounds 5e, 5g and 5i have showed potent activities only on hormone‐independent prostate cancer cell lines DU‐145 and PC‐3 with 60–85% inhibition of both cell viability and growth at 10 nm with pro‐apoptotic mechanism as illustrated in PC‐3 cells by DNA ladder assay and Western blotting of Bax, Casp‐3 and its substrate, the poly (ADP–ribose) polymerase. We conclude that hybrid heterocycle steroids could be good lead compounds in the drug design especially against hormone‐independent prostate cancer.