4'-(pivaloylamino)acetophenone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4'-(pivaloylamino)acetophenone
• 英文别名: N-(4-acetylphenyl)-2,2-dimethylpropanamide
• 化学式: C₁₃H₁₇NO₂
• mdl: MFCD00584423
• 分子量: 219.283
• InChiKey: FXAGRBAPRNMVOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4'-(pivaloylamino)acetophenone 在 盐酸 、 sodium hydride 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 5.0h， 生成 5-(N-Pivaloyl)amino-2-[4-(N-pivaloyl)amino]phenyl-4H-benzopyran-4-one
  参考文献：
  名称：

  Novel 5-Aminoflavone Derivatives as Specific Antitumor Agents in Breast Cancer

  摘要：

  In the course of our search for new antitumor agents in breast cancer, novel amino-substituted flavone derivatives were synthesized and examined for antitumor activities. Among them, 5,4'-diaminoflavone and some of its congeners showed remarkable antiproliferative activity against the estrogen receptor (ER)-positive and estrogen-responsive human breast cancer cell line MCF-7. The activity was observed irrespective of the presence or absence of estrogen. The 5-aminoflavone derivatives (5-AFs) are not classical anti-estrogens because they did not compete with [H-3]estradiol to bind the estrogen receptor. Moreover, 5-AFs showed antitumor activity highly selective to the ER-positive breast cancer cell line, and they showed no effects against the ER-negative human cancer cell lines HeLa S-3, WiDr, and MDA-MB-453. Although the mechanism of their selective antitumor activity to ER-positive breast cancer cells is unclear, 5-AFs are expected to be a new type of antitumor agents in breast cancer.

  DOI：

  10.1021/jm950938g
• 作为产物：
  描述：

  4-乙酰苯基异氰酸酯 、 三甲基乙酸 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以88%的产率得到4'-(pivaloylamino)acetophenone
  参考文献：
  名称：

  Facile Amide Bond Formation from Carboxylic Acids and Isocyanates

  摘要：

  A wide variety of carboxylic acids in the form of their salts condense with aryl isocyanates at room temperature with loss of carbon dioxide to give the corresponding amides in high yield. Application of the reaction to acyl isocyanates gives unsymmetric imides. The reaction is compatible with hydroxyl groups and both Fmoc and Boc protecting groups for amines and is applicable to aliphatic, aromatic, and heteroaromatic acids.

  DOI：

  10.1021/ol200531k

文献信息

• General rhodium-catalyzed oxidative cross-coupling reactions between anilines: synthesis of unsymmetrical 2,2′-diaminobiaryls
  作者：Yang Shi、Jiahui Liu、Yudong Yang、Jingsong You

  DOI：10.1039/c9cc01733j

  日期：——

  cross-coupling reactions. Furthermore, this Cp*-free catalytic reaction tolerates a range of functional groups and requires only a low molar ratio of coupling partners. These features expedite the synthesis of unsymmetrical 2,2′-diaminobiaryls.

  本文描述的是苯胺衍生物的双重螯合辅助RhCl 3催化的氧化C–H / C–H交叉偶联反应。该方法的重点是电子相似底物之间的化学和区域选择性交叉偶联，这在氧化性Ar–H / Ar–H交叉偶联反应中是一项极富挑战性的任务。此外，这种无Cp *的催化反应可耐受一定范围的官能团，并且仅需要低摩尔比的偶联配偶体。这些特征加速了不对称的2，2′-二氨基联芳基的合成。
• Design and Synthesis of Potent Antitumor 5,4‘-Diaminoflavone Derivatives Based on Metabolic Considerations
  作者：Tsutomu Akama、Hiroyuki Ishida、Yasushi Shida、Uichiro Kimura、Katsushige Gomi、Hiromitsu Saito、Eiichi Fuse、Satoshi Kobayashi、Nobuyuki Yoda、Masaji Kasai

  DOI：10.1021/jm9700326

  日期：1997.6.1

  Recently, we reported that 5,4'-diaminoflavone (1) exhibits potent and specific growth-inhibitory activity against the estrogen receptor (ER)-positive human breast cancer cell line MCF-7. However, when compound 1 was incubated with S-9 mix, its metabolites were observed. Moreover, addition of S-9 mix to the medium caused the drastic decrease in activity of compound 1. Since the 6-, 8-, and 3'-positions

  最近，我们报道了5,4'-二氨基黄酮（1）对雌激素受体（ER）阳性的人乳腺癌细胞系MCF-7表现出有效的特异性生长抑制活性。但是，将化合物1与S-9混合物一起孵育时，会观察到其代谢产物。此外，向培养基中添加S-9混合物会导致化合物1的活性急剧降低。由于从MO计算中认为6-，8-和3'-位在体内被氧化代谢，因此一系列5针对这些代谢上稳定的衍生物，合成了在这样的假定的代谢位置上被各种官能团取代的，4'-二氨基黄酮衍生物。其中，即使在存在S-9混合物的情况下，5,4'-二氨基-6,8,3'-三氟黄酮（14d）对MCF-7细胞也显示出较强的生长抑制活性。而且，口服给药的化合物14d完全抑制了接种到裸鼠中的MCF-7的生长，并且其作用比化合物1更为有效。除了ER阳性乳腺癌细胞之外，化合物14d还显示出对一组人的生长抑制活性。人癌细胞系，包括部分ER阴性乳腺癌，子宫内膜癌，卵巢癌和肝癌。从这些结果，阐
• 5-aminoflavone derivatives
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US05539112A1

  公开（公告）日：1996-07-23

  5-Aminoflavone derivatives represented by the formula (I): ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and represent hydrogen, substituted or unsubstituted lower alkyl, lower alkenyl, halogen-substituted or unsubstituted lower alkanoyl or lower alkoxycarbonyl, X.sup.1, X.sup.2, Y.sup.1 and Y.sup.2 are the same or different and represent hydrogen, halogen or lower alkyl, at least one of X.sup.1 and X.sup.2 represents halogen or lower alkyl, X.sup.3 represents hydrogen, substituted or unsubstituted lower alkyl, lower alkenyl, lower alkynyl, halogen, hydroxy, substituted or unsubstituted lower alkoxy, NR.sup.5 R.sup.6 (wherein R.sup.5 and R.sup.6 are the same or different and represent hydrogen, or substituted or unsubstituted lower alkyl, or R.sup.5 and R.sup.6 are taken together to form a heterocyclic group containing the nitrogen atom in the ring), lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, carboxy, lower alkoxycarbonyl, lower alkanoyl, adizo, cyano, substituted or unsubstituted carbamoyl or lower alkylthiothiocarbonyl: or pharmaceutically acceptable salts thereof.

  5-氨基黄酮衍生物的化学式（I）如下：其中R.sup.1、R.sup.2、R.sup.3和R.sup.4相同或不同，代表氢、取代或未取代的较低烷基、较低烯基、卤素取代或未取代的较低烷酰基或较低烷氧羰基，X.sup.1、X.sup.2、Y.sup.1和Y.sup.2相同或不同，代表氢、卤素或较低烷基，X.sup.1和X.sup.2中至少一个代表卤素或较低烷基，X.sup.3代表氢、取代或未取代的较低烷基、较低烯基、较低炔基、卤素、羟基、取代或未取代的较低烷氧基、NR.sup.5 R.sup.6（其中R.sup.5和R.sup.6相同或不同，代表氢，或取代或未取代的较低烷基，或R.sup.5和R.sup.6一起形成含有环中氮原子的杂环基），较低烷硫基、较低烷硫醇基、较低烷硫酰基、羧基、较低烷氧羰基、较低烷酰基、阿狄佐基、氰基、取代或未取代的氨基羰基或较低烷硫基硫羰基：或其药用盐。
• Palladium(II)-Catalyzed Direct ortho-CH Acylation of Anilides by Oxidative Cross-Coupling with Aldehydes using tert-Butyl Hydroperoxide as Oxidant
  作者：Chun-Wo Chan、Zhongyuan Zhou、Wing-Yiu Yu

  DOI：10.1002/adsc.201100472

  日期：2011.11

  An efficient palladium-catalyzed CH acylation with aldehydes using tert-butyl hydroperoxide (TBHP) transforms various anilides into synthetically useful 2-aminobenzophenone derivatives under mild conditions (40 °C, 3 h). The acylation reaction exhibits excellent regioselectivity and functional group tolerance, and simple aromatic aldehydes, functionalized aliphatic aldehydes and heteroaromatic aldehydes

  使用叔丁基氢过氧化物（TBHP）进行的钯与醛的有效CH酰化CH酰化反应可在温和条件下（40°C，3 h）将各种酸酐转化为合成有用的2-氨基二苯甲酮衍生物。酰化反应显示出优异的区域选择性和官能团耐受性，简单的芳族醛，官能化的脂族醛和杂芳族醛是有效的偶联伙伴。酰化反应可能是通过限速亲电CH环钯反应（k H / k D = 3.6;ρ + = -0.74）引发，形成芳基钯配合物，然后进行酰基自由基官能化。
• 5- Aminoflavone derivatives
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP0374789A1

  公开（公告）日：1990-06-27

  Novel 5-ammoflavone derivatives represented by formula (I) and pharmaceutically acceptable salts thereof are disclosed. The 5-aminoflavone derivatives have anticellular activity and are expected to be useful as antitumor agents.

  公开了由式（I）表示的新颖的5-氨基黄酮衍生物及其药用可接受的盐。这些5-氨基黄酮衍生物具有抗细胞活性，预计可用作抗肿瘤药物。