2-bromo-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide | 1225441-13-3

• 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: 2-bromo-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide
• 英文别名: 2-bromo-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
• CAS: 1225441-13-3
• 化学式: C₁₁H₁₀BrF₃N₂O₃
• 分子量: 355.111
• InChiKey: JYQFYSAOJHXVMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-bromo-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide 在 silver fluoride 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以71%的产率得到fluoro-flutamide
  参考文献：
  名称：

  银促进的α-溴酰胺的氟化反应

  摘要：

  据报道，在温和的条件下使用AgF可以在α-溴酰胺中形成银促进的CF键形成。这种简单的方法可以访问涉及生物分子支架的叔，仲和伯烷基氟化物。这种转变适用于伯酰胺和仲酰胺，并显示出广泛的官能团耐受性。动力学实验表明，反应速率按3°> 2°> 1°α-碳原子的顺序增加。另外，发现酸性酰胺质子在促进反应中起重要作用。机理研究表明，生成叠氮醌中间体，然后对其进行亲核加成以形成具有立体特异性（即保留构型）的CF键。Ag I合成位阻醇和醚也得到了证明。给出了α-溴酰胺与O亲核试剂反应的例子。

  DOI：

  10.1002/chem.202004769
• 作为产物：
  描述：

  2-溴-2-甲基丙酸 、 5-氨基-2-硝基三氟甲苯 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以12%的产率得到2-bromo-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide
  参考文献：
  名称：

  Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

  摘要：

  In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide-or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono-and difluoro-substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC50 values of 41.8 mu M (for LNCaP) and 39.1 mu M (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-anti-androgen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, anti-androgens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.011

文献信息

• Trifluoromethylthiolation of Hindered α-Bromoamides with Nucleophilic Trifluoromethylthiolating Reagents
  作者：Satoshi Mizuta、Kanami Kitamura、Yuki Morii、Jun Ishihara、Tomoko Yamaguchi、Takeshi Ishikawa

  DOI：10.1021/acs.joc.1c02316

  日期：2021.12.17

  General methods have not been previously developed for the synthesis of sterically hindered α-SCF3-substituted carbonyl compounds using nucleophilic trifluoromethylthiolating reagents. Thus, we herein report sp3C–SCF3 bond formation in hindered α-bromoamides containing 3-bromo-oxindoles and linear α-bromoamides using CuSCF3 or AgSCF3 under mild conditions to access sterically hindered α-SCF3-substituted

  以前尚未开发出使用亲核三氟甲基硫醇化试剂合成位阻α-SCF 3 -取代的羰基化合物的通用方法。因此，我们在此报告了在温和条件下使用 CuSCF 3或 AgSCF 3在含有 3-溴代羟吲哚和线性 α-溴酰胺的受阻 α-溴酰胺中形成sp 3 C-SCF 3键以获得空间位阻 α-SCF 3取代的酰胺。这种转变不仅适用于 3-SCF 3 -取代的羟吲哚，而且适用于伯和仲酰胺，并显示出广泛的官能团耐受性。这种方法将有利于医药和农业化学领域。
• Zinc‐Mediated Radiosynthesis of Unprotected Fluorine‐18 Labelled α‐Tertiary Amides
  作者：Jay S. Wright、Richard Ma、E. William Webb、Wade P. Winton、Jenelle Stauff、Kevin Cheng、Allen F. Brooks、Melanie S. Sanford、Peter J. H. Scott

  DOI：10.1002/anie.202316365

  日期：2024.1.8

  A high-yielding radiofluorination of unprotected α-tertiary haloamides is described. This method provides a new strategy for radiochemists to install fluorine-18 into sterically protected environments for positron emission tomography imaging. Preliminary mechanistic studies were leveraged to develop a novel C−H radiofluorination reaction of N-sulphonyloxyamides.

  描述了未受保护的 α-叔卤代酰胺的高产率放射性氟化。该方法为放射化学家将氟 18 安装到空间保护环境中进行正电子发射断层扫描成像提供了一种新策略。利用初步的机理研究开发了一种新型的N-磺酰氧基酰胺的 C−H 放射性氟化反应。
• Use of estrogens or antiandrogens for reversal of male sexual phenotype in poultry
  申请人：MERCK & CO. INC.

  公开号：EP0514056A2

  公开（公告）日：1992-11-19

  Fertilized poultry embryos are treated with estrogens or antiandrogens or estrogens in combination with antiandrogens during a period of embryonic development when the gonads are bipotential. This treatment causes genetic males to exhibit a female phenotype. When sex reversed male birds are crossed with normal male birds all offspring will be genotypically male.

  受精的家禽胚胎在胚胎发育期间，性腺处于双潜能期，此时使用雌激素或抗雄激素，或雌激素与抗雄激素联合使用。这种处理方法会使遗传雄性表现出雌性表型。当性别逆转的雄性鸟类与正常雄性鸟类杂交时，所有后代的基因型都是雄性。
• US5994362A
  申请人：——

  公开号：US5994362A

  公开（公告）日：1999-11-30
• [EN] PHARMACEUTICAL COMBINATION FOR THE TREATMENT OF PROSTATIC CANCER CONTAINING A 5 ALPHA REDUCTASE INHIBITOR AND AN ANTIANDROGEN
  申请人：MERCK & CO., INC.

  公开号：WO1992016233A1

  公开（公告）日：1992-10-01

  (EN) Disclosed is a new treatment for men with prostatic cancer involving combination therapy of a 5$g(a)-reductase inhibitor, i.e., a 17$g(b)-substituted 4-azasteroid, a 17$g(b)-substituted non-azasteroid, 17$g(b)-acyl-3-carboxyandrost-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylamino-phenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, and particularly finasteride, in combination with an antiandrogen, i.e. flutamide. Pharmaceutical compositions useful for treatment are also disclosed.(FR) Nouveau traitement destiné à des hommes atteints d'un cancer de la prostate, impliquant la thérapie combinée à l'aide d'un inhibiteur de 5$g(a)-réductase, c'est à dire un 4-azastéroide 17$g(b)-substitué, un non-azastéroide 17$g(b)-substitué, 17$g(b)-acyl-3-carboxyandrost-3,5-diène, un dérivé d'acide benzoylaminophénoxybutanoique, un dérivé fusionné de benz(thio)amide ou de cinnamoylamide, des 1,2-diéthers ou thioéthers aromatiques, des acides alcanoiques aromatiques orthoacylaminophénoxy, leurs sels et leurs esters pharmaceutiquement acceptables, et en particulier un finastéride, en combinaison avec un antiandrogène, c'est à dire un flutamide. L'invention concerne également des compositions pharmaceutiques utilisées dans le traitement du cancer de la prostate.