(S)-2-chloro-7-(2,2-dimethyl-[1,3]dioxolan-4-yl)methoxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one | 1353948-59-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: (S)-2-chloro-7-(2,2-dimethyl-[1,3]dioxolan-4-yl)methoxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one
• 英文别名: 2-chloro-7-(S-1,2-isopropylidenglycer-3-yl)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one；13-chloro-5-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]tricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-one
• CAS: 1353948-59-0
• 化学式: C₂₁H₂₁ClO₄
• 分子量: 372.848
• InChiKey: ADANUOPKCCNVTF-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-chloro-7-(2,2-dimethyl-[1,3]dioxolan-4-yl)methoxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one 在 palladium diacetate 、 对甲苯磺酸 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲醇 、 水 、 甲苯 、 叔丁醇 为溶剂， 反应 8.0h， 生成 2-(2-aminophenylamino)-7-[2R-,3-dihydroxypropoxy]-10,11-dihydro-dibenzo[a,d]-cyclohepten-5-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Disubstituted Dibenzosuberones as Highly Potent and Selective Inhibitors of p38 Mitogen Activated Protein Kinase

  摘要：

  Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC50) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kinase compared to other kinases indicate them to be most applicable as tools in pharmacological research and eventually they may foster a new generation of anti-inflammatory drugs.

  DOI：

  10.1021/jm300327h
• 作为产物：
  描述：

  2-formyl-5-methoxy-benzoic acid 在 氯化亚砜 、 palladium on activated charcoal 、 氢溴酸 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 39.0h， 生成 (S)-2-chloro-7-(2,2-dimethyl-[1,3]dioxolan-4-yl)methoxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Disubstituted Dibenzosuberones as Highly Potent and Selective Inhibitors of p38 Mitogen Activated Protein Kinase

  摘要：

  Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC50) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kinase compared to other kinases indicate them to be most applicable as tools in pharmacological research and eventually they may foster a new generation of anti-inflammatory drugs.

  DOI：

  10.1021/jm300327h

文献信息

• DIBENZOCYCLOHEPTATONE DERIVATIVES AND PHARMACEUTICAL AGENTS CONTAINING SAID COMPOUNDS
  申请人：Laufer Stefan

  公开号：US20120115862A1

  公开（公告）日：2012-05-10

  The present invention relates to compounds of the formula I wherein R1, R2, R3, R4, X and Y have the meanings given in the description. The compounds have an action which is immunomodulating and inhibits or regulates the release of IL-1β and/or TNF-α. They can therefore be used for treatment of diseases connected with a disturbance in the immune system.

  本发明涉及公式I中的化合物，其中R1、R2、R3、R4、X和Y的含义如描述中所述。这些化合物具有免疫调节作用，并抑制或调节IL-1β和/或TNF-α的释放。因此，它们可以用于治疗与免疫系统紊乱有关的疾病。
• Dibenzosuberones as p38 Mitogen-Activated Protein Kinase Inhibitors with Low ATP Competitiveness and Outstanding Whole Blood Activity
  作者：Stefan Fischer、Heike K. Wentsch、Svenja C. Mayer-Wrangowski、Markus Zimmermann、Silke M. Bauer、Kirsten Storch、Raimund Niess、Solveigh C. Koeberle、Christian Grütter、Frank M. Boeckler、Daniel Rauh、Stefan A. Laufer

  DOI：10.1021/jm301539x

  日期：2013.1.10

  p38 alpha mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38 alpha MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.