17-picolinylideneandrost-4-ene-3-one | 960313-58-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 17-picolinylideneandrost-4-ene-3-one
• 英文别名: 3β-hydroxy-17-picolinylideneandrost-4-en-3-one；17(E)-(2-picolinylidene)androst-4-en-3-one；(8S,9S,10R,13S,14S,17E)-10,13-dimethyl-17-(pyridin-2-ylmethylidene)-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 960313-58-0
• 化学式: C₂₅H₃₁NO
• 分子量: 361.527
• InChiKey: RGNJSZWUMOCIKE-RHCHAJQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  17-picolinylideneandrost-4-ene-3-one 在 盐酸羟胺 、 sodium acetate 、 potassium carbonate 作用下， 以 乙醇 、 丁酮 为溶剂， 反应 51.5h， 生成 (17E)-(pyridin-2-yl)methylideneandrost-4-en-(3E)-one O-[3-(N,N-dimethylamino)propyl] oxime
  参考文献：
  名称：

  雄甾烷 3-肟的新型烷基氨基乙基衍生物作为抗癌候选物：细胞毒性作用的合成和评价

  摘要：

  类固醇抗癌药物是众多科学研究工作的重点。由于它们对肿瘤细胞的高细胞毒性作用，一些天然或合成的类固醇化合物似乎有望用于治疗不同类别的癌症。在本研究中，使用不同的烷基氨基乙基氯化物，从异构纯的 3 E-肟合成了 14 种新型O-烷基化 oxyimino androst -4-ene 衍生物。他们的体外针对八种人类癌细胞系以及正常胎肺 (MRC-5) 和人类包皮 (BJ) 成纤维细胞评估了细胞毒活性，以测试化合物的效率和选择性。大多数衍生物对恶性黑色素瘤 (G-361)、肺腺癌 (A549) 和结肠腺癌 (HT-29) 细胞系表现出很强的活性。使用迁移划痕和管形成试验对 HUVEC 细胞进行体外血管生成评估，其中观察到 17α-(pyridin-2-yl)methyl 2-(morpholin-4-yl)ethyl 衍生物对内皮细胞迁移的部分抑制。在最损害肺癌 A549 细胞生长的化合物中，(17

  DOI：

  10.1039/d1ra07613b
• 作为产物：
  描述：

  3β-acetoxy-17-picolinylidene-androst-5-ene 在 环己酮 、 aluminum isopropoxide 、 potassium hydroxide 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 3.0h， 生成 17-picolinylideneandrost-4-ene-3-one
  参考文献：
  名称：

  评估 A 环稠合吡啶 d-修饰的雄甾烷衍生物的抗增殖和醛酮还原酶 1C3 抑制活性†

  摘要：

  合成了 17a-homo-17-oxa ( D -homo lactone)、17α-甲基吡啶或 17( E )-甲基吡啶系列中的新型 A 环吡啶稠合雄甾烷，并通过 X 射线晶体学、HRMS、IR 和 NMR 光谱学进行了验证。新型化合物3 , 5 , 8和12通过 Cu( II )催化的炔丙基胺处理 4-en-3-one 或 4-ene-3,6-dione D-修饰的雄甾烷衍生物制备，并评估其潜在的抗癌作用体外活性使用人类癌细胞系和甾体抗癌药物的重组靶点。吡啶与 A 环的 3,4 位融合可显着增强 17α-吡啶甲基化合物对 CYP17 的亲和力，同时赋予对 PC-3 细胞的选择性抗增殖活性。类似地，吡啶与甾体D-同型内酯的 A 环融合导致发现了醛酮还原酶 1C3 的新抑制剂，这是一种针对急性髓性白血病、乳腺癌和前列腺癌的酶。一A-吡啶D-内酯类固醇5对 HT-29 结肠癌细胞还具有选择性

  DOI：

  10.1039/c8md00077h

文献信息

• 17(E)-Picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: Antiproliferative activity and molecular docking studies
  作者：Jovana J. Ajduković、Evgenija A. Djurendić、Edward T. Petri、Olivera R. Klisurić、Andjelka S. Ćelić、Marija N. Sakač、Dimitar S. Jakimov、Katarina M. Penov Gaši

  DOI：10.1016/j.bmc.2013.09.063

  日期：2013.12

  17α-picolyl and 17(E)-picolinylidene androstane derivatives from dehydroepiandrosterone. Compounds were validated spectroscopically and structurally characterized by X-ray crystallography. Virtual screening by molecular docking against clinical targets of steroidal anticancer drugs (ERα, AR, Aromatase and CYP17A1) suggests that 17(E)-picolinylidene, but not 17α-picolyl androstanes could specifically interact

  我们报告了快速有效的合成A环修饰从脱氢表雄酮的17α-picolyl和17（E）-picolinylidene androstane衍生物。通过X射线晶体学在光谱上和结构上对化合物进行了验证。通过分子对接针对类固醇抗癌药物（ERα，AR，Aromatase和CYP17A1）的临床靶点进行的虚拟筛选表明，17（E）-吡啶甲基亚烷基，而不是17α-吡啶基雄烷可以与具有相似几何形状和相似结构的CYP17A1（17α-羟化酶）特异性相互作用亲和力为阿比特龙，一种临床上用于治疗前列腺癌的17-吡啶基雄烷类药物。另外，几个17（E）-吡啶甲酸亚吡喃雄酮对PC3前列腺癌细胞表现出选择性的抗增殖活性，与Abiraterone的抗增殖活性和预测的CYP17A1结合亲和力相关。基于这些初步结果，17（E）-吡啶甲基亚烷基雄烷烃衍生物可能是开发用于治疗前列腺癌的新化合物的有希望的起点。
• Novel D-modified heterocyclic androstane derivatives as potential anticancer agents: Synthesis, characterization, in vitro and in silico studies
  作者：Tijana Lj. Šestić、Jovana J. Ajduković、Sofija S. Bekić、Andjelka S. Ćelić、Sanja T. Stojanović、Stevo J. Najman、Maja A. Marinović、Edward T. Petri、Dušan Đ. Škorić、Marina P. Savić

  DOI：10.1016/j.jsbmb.2023.106362

  日期：2023.10

  Based on in vitro binding assays, N-formyl lactam compound 18 appeared to be the strong and isoform-selective ligand for ERα, while compound 9A displayed binding affinity for the GR-LBD, but also inhibited aldo-keto reductase 1C4 enzyme. Out of four selected compounds, methylpyrazolo derivative 13 showed potential for aromatase binding, while in silico studies provided insight into experimentally confirmed

  癌症仍然是全世界的主要健康问题。最常诊断出的癌症类型是由类固醇激素的异常产生或作用引起的。在本研究中，介绍了具有D-高内酯、17α-(吡啶-2''-基甲基)或17( E )-(吡啶-2''-基亚甲基)部分的新型杂环雄甾烷衍生物的合成和结构表征。所有化合物均针对 HeLa 宫颈癌细胞系和非癌性肾 MDCK 细胞的抗增殖活性进行了评估，其中 A-同型内酰胺化合物9A显示出最大的选择性。根据体外结合测定，N-甲酰内酰胺化合物18似乎是 ERα 的强异构体选择性配体，而化合物9A显示出对 GR-LBD 的结合亲和力，但也抑制醛酮还原酶 1C4 酶。在四种选定的化合物中，甲基吡唑并衍生物13显示出与芳香酶结合的潜力，而计算机研究则提供了对实验证实的蛋白质-配体相互作用的深入了解。
• Synthesis and biological evaluation of some 17-picolyl and 17-picolinylidene androst-5-ene derivatives
  作者：Katarina M. Penov Gaši、Maja Dj. Djurendić Brenesel、Evgenija A. Djurendić、Marija N. Sakač、Janoš J. Čanadi、Jovana J. Daljev、Thomas Armbruster、Silvana Andrić、Dušan M. Sladić、Tatjana T. Božić、Irena T. Novaković、Zorica D. Juranić

  DOI：10.1016/j.steroids.2006.10.002

  日期：2007.1

  Starting from dehydroepiandrosterone (1) 17-picolyl (2), 17-picolinylidene (7), 17-picolinylidene-16-one (10 and 11), and 17-picolyl-16-one (15) derivatives of androst-5-ene were synthesized in one, two, four and five steps respectively. By the Oppenauer oxidation or dehydration of 2, 7, 10, and 11 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the corresponding A and B ring modified derivatives 3, 5, 6, 8, 9, and 12-14 were obtained. The structure of 2 was unambiguously proved by the appropriate X-ray structural analysis. Compounds 3, 5,9,12-14 showed inhibitory activity against the enzyme aromatase. Antibacterial activity toxicity to brine shrimp Artemia salina, antitumor activity against three tumor cell lines (human cervix carcinoma HeLa cells, human melanoma FemX cells, and human myelogenous leukemia K562 cells) and toxicity against peripheral blood mononuclear cells were evaluated. Three tested compounds, namely 11, 13, and 15, showed strong activity against all three cell lines, the IC50 values being in the range of 4-10 mu M. (c) 2006 Elsevier Inc. All rights reserved.
• Synthesis of some epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives and evaluation of their biological activity
  作者：Evgenija Djurendić、Jovana Daljev、Marija Sakač、Janoš Čanadi、Suzana Jovanović Šanta、Silvana Andrić、Olivera Klisurić、Vesna Kojić、Gordana Bogdanović、Maja Djurendić-Brenesel、Sladjana Novaković、Katarina Penov Gaši

  DOI：10.1016/j.steroids.2007.09.005

  日期：2008.1

  Steroidal epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives have been prepared using 3 beta,17 beta-dihydroxy-17 alpha-picolyl-androst-5-ene (1), 3 beta-acetoxy-17-picolinylidene-androst-5-ene (2), and 3 beta-hydroxy-17-picolinylidene-androst-5-ene (3) as synthetic precursors. The compounds 2 and/or 3 were reacted with m-chloroperoxybenzoic acid (MCPBA). The compounds synthesized from 2 were 17-picolinylidene-N-oxide 4, 5 alpha,6 alpha-epoxy and 5 beta,6 beta-epoxy-17-picolinylidene-N-oxide 5 and 6, and 5 alpha,6 alpha:17 alpha,2 alpha and 5 beta,6 beta:17 alpha,20 alpha-diepoxy-N-oxide 7 and 8. Starting from compound 3, a mixture of 5 alpha,6 alpha-epoxy and 5 beta,6 beta-epoxy-17-picolinylidene 9 and 10, 5 alpha,6 alpha-epoxy and 5 beta,6 beta-epoxy-17-picolinylidene-N-oxide 11 and 12, and 5 alpha,6 alpha:17 alpha,20 alpha- and 5 beta,6 beta:17 alpha,20 alpha-diepoxy-N-oxide 13 and 14 were obtained. From compounds 15 and 18, obtained from 1 and 3 by the Oppenauer oxidation, the 4 alpha,5 alpha-epoxy and 4 beta,5 beta-epoxy derivatives 16, 17 and 20, 21 were prepared by oxidation with 30% H2O2 Oxidation of 18 with MCPBA yielded only the N-oxide 19. The structures of compounds 15 and 18 were proved by the X-ray analysis. Compounds 1-6, 9, 15, 17, 18, and 21 were tested on activity against the enzyme aromatase. Antitumor activity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, and prostate cancer PC3) was evaluated. Three tested compounds (1, 4, and 19) showed strong activity against PC3, the IC50 values being in the range 0.55-10 mu M, whereas compound 17 showed strong activity against MDA-MB-231 (IC50 10.4 mu M). (C) 2007 Elsevier Inc. All rights reserved.
• Novel alkylaminoethyl derivatives of androstane 3-oximes as anticancer candidates: synthesis and evaluation of cytotoxic effects
  作者：Jovana J. Ajduković、Dimitar S. Jakimov、Lucie Rárová、Miroslav Strnad、Yaraslau U. Dzichenka、Sergey Usanov、Dušan Đ. Škorić、Suzana S. Jovanović-Šanta、Marija N. Sakač

  DOI：10.1039/d1ra07613b

  日期：——

  Steroid anticancer drugs are the focus of numerous scientific research efforts. Due to their high cytotoxic effects against tumor cells, some natural or synthetic steroid compounds seem to be promising for the treatment of different classes of cancer. In the present study, fourteen novel O-alkylated oxyimino androst-4-ene derivatives were synthesized from isomerically pure 3E-oximes, using different

  类固醇抗癌药物是众多科学研究工作的重点。由于它们对肿瘤细胞的高细胞毒性作用，一些天然或合成的类固醇化合物似乎有望用于治疗不同类别的癌症。在本研究中，使用不同的烷基氨基乙基氯化物，从异构纯的 3 E-肟合成了 14 种新型O-烷基化 oxyimino androst -4-ene 衍生物。他们的体外针对八种人类癌细胞系以及正常胎肺 (MRC-5) 和人类包皮 (BJ) 成纤维细胞评估了细胞毒活性，以测试化合物的效率和选择性。大多数衍生物对恶性黑色素瘤 (G-361)、肺腺癌 (A549) 和结肠腺癌 (HT-29) 细胞系表现出很强的活性。使用迁移划痕和管形成试验对 HUVEC 细胞进行体外血管生成评估，其中观察到 17α-(pyridin-2-yl)methyl 2-(morpholin-4-yl)ethyl 衍生物对内皮细胞迁移的部分抑制。在最损害肺癌 A549 细胞生长的化合物中，(17