3,4,5-trimethoxybenzoic acid 4-oxocyclohexyl ester | 929548-57-2

• 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: 3,4,5-trimethoxybenzoic acid 4-oxocyclohexyl ester
• 英文别名: (4-Oxocyclohexyl) 3,4,5-trimethoxybenzoate
• CAS: 929548-57-2
• 化学式: C₁₆H₂₀O₆
• 分子量: 308.331
• InChiKey: PKSGAWAPEVRXNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,4,5-trimethoxybenzoic acid 4-oxocyclohexyl ester 在 titanium(IV) isopropylate 、 sodium cyanoborohydride 作用下， 以 乙醇 、 苯 为溶剂， 反应 23.0h， 生成 cis/cis-3,4,5-trimethoxybenzoic acid 4-(4-hydroxycyclohexylamino)cyclohexyl ester
  参考文献：
  名称：

  Isomeric N,N-Bis(cyclohexanol)amine Aryl Esters:  The Discovery of a New Class of Highly Potent P-Glycoprotein (Pgp)-dependent Multidrug Resistance (MDR) Inhibitors

  摘要：

  A new series of P-glycoprotein (Pgp)-dependent multidrug resistance (MDR) inhibitors having a N,N-bis(cyclohexanol)amine scaffold have been designed, following the frozen analog approach. With respect to the parent flexible molecules, the new compounds show improved potency and efficacy. Among them, compound 1d, on anthracycline-resistant erythroleukemia K562 cells, is able to completely reverse Pgp-dependent MDR at low nanomolar concentration.

  DOI：

  10.1021/jm0614432
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酸 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 12.0h， 生成 3,4,5-trimethoxybenzoic acid 4-oxocyclohexyl ester
  参考文献：
  名称：

  Isomeric N,N-Bis(cyclohexanol)amine Aryl Esters:  The Discovery of a New Class of Highly Potent P-Glycoprotein (Pgp)-dependent Multidrug Resistance (MDR) Inhibitors

  摘要：

  A new series of P-glycoprotein (Pgp)-dependent multidrug resistance (MDR) inhibitors having a N,N-bis(cyclohexanol)amine scaffold have been designed, following the frozen analog approach. With respect to the parent flexible molecules, the new compounds show improved potency and efficacy. Among them, compound 1d, on anthracycline-resistant erythroleukemia K562 cells, is able to completely reverse Pgp-dependent MDR at low nanomolar concentration.

  DOI：

  10.1021/jm0614432

文献信息

• N -alkanol- N -cyclohexanol amine aryl esters: Multidrug resistance (MDR) reversing agents with high potency and efficacy
  作者：Elisabetta Teodori、Silvia Dei、Marcella Coronnello、Elisa Floriddia、Gianluca Bartolucci、Dina Manetti、Maria Novella Romanelli、Diego Santo Domingo Porqueras、Milena Salerno

  DOI：10.1016/j.ejmech.2017.01.019

  日期：2017.2

  (reversal fold, RF) and inhibition of P-gp-mediated rhodamine-123 (Rhd 123) efflux tests. The chemical stability of their ester function was evaluated in the experimental conditions utilized (phosphate buffer solution (PBS), bovine serum and in the presence of K562/DOX cells) and in human plasma. The new series of molecules showed very interesting MDR reversing properties; in particular compound 5b (ELF26B)

  在继续寻找有效的P-gp依赖的耐多药（MDR）反向剂的过程中，我们合成并研究了一系列新的N-链烷醇-N-环己醇胺芳基酯，其特征是存在两个具有不同柔性的接头：聚亚甲基链长度可变且带有环己基骨架，这产生了两个几何异构体（顺式和反式）。通过三种测试在K562 / DOX细胞系上评估了新化合物的逆转活性：吡柔比星摄取调节，阿霉素细胞毒性增强（逆向折叠，RF）和对P-gp介导的若丹明-123（Rhd 123）流出测试的抑制作用。 。在所使用的实验条件（磷酸盐缓冲溶液（PBS），牛血清以及在K562 / DOX细胞存在下）和人血浆中评估了其酯功能的化学稳定性。新的分子系列显示出非常有趣的MDR逆转特性；特别是具有反式立体化学和5-亚甲基链特征的化合物5b（ELF26B）表现出最好的药理学特性，并且在每种被测培养基中都稳定。化合物5b可能是开发新型有效的依赖P-gp的MDR调节剂的有趣线索。
• [EN] N-BENZYL-3-INDENYLACETAMIDES DERIVATIVES FOR TREATING NEOPLASIA<br/>[FR] DERIVES DE N-BENZYL-3-INDENYLACETAMIDES POUR TRAITER DES NEOPLASIES
  申请人：CELL PATHWAYS, INC.

  公开号：WO1999031065A1

  公开（公告）日：1999-06-24

  (EN) Substituted condensation products of N-benzyl-3-indenylacetamides of formula (I) with heterocyclic aldehydes are useful for inducing or promoting apoptosis and for arresting uncontrolled neoplastic cell proliferation, and are specifically useful in the arresting and treatment of neoplasias, including precancerous and cancerous lesions.(FR) L'invention concerne des produits de condensation substitués de N-benzyl-3-indénylacétamides de formule (I) avec des aldéhydes hétérocycliques, qui sont utiles pour provoquer ou activer l'apoptose et pour enrayer une prolifération incontrôlée de cellules néoplasiques, et spécifiquement utiles pour enrayer et traiter des néoplasies, y compris des lésions précancéreuses et cancéreuses.

  (EN) 公式（I）的N-苄基-3-茚烯乙酰胺的取代缩合产物与杂环醛的反应产物，可用于诱导或促进细胞凋亡并阻止不受控制的肿瘤细胞增殖，特别适用于阻止和治疗肿瘤，包括癌前病变和癌症病变。 (FR) 公式（I）的N-苄基-3-茚烯乙酰胺的取代缩合产物与杂环醛的反应产物，可用于诱导或促进细胞凋亡并阻止不受控制的肿瘤细胞增殖，特别适用于阻止和治疗肿瘤，包括癌前病变和癌症病变。
• <i>N</i>,<i>N</i>-bis(Cyclohexanol)amine Aryl Esters: A New Class of Highly Potent Transporter-Dependent Multidrug Resistance Inhibitors
  作者：Cecilia Martelli、Daniela Alderighi、Marcella Coronnello、Silvia Dei、Maria Frosini、Bénédicte Le Bozec、Dina Manetti、Annalisa Neri、Maria Novella Romanelli、Milena Salerno、Serena Scapecchi、Enrico Mini、Giampietro Sgaragli、Elisabetta Teodori

  DOI：10.1021/jm8012745

  日期：2009.2.12

  A new series of Pgp-dependent MDR inhibitors having a N,N-bis(cyclohexanol)amine scaffold was designed on the basis of the frozen analogue approach. The scaffold chosen gives origin to different geometrical isomers. The new compounds showed a wide range of potencies and efficacies on doxorubicin-resistant erythroleukemia K562 cells in the pirarubicin uptake assay. The most interesting compounds (isomers of 3) were studied further evaluating their action on the ATPase activity present in rat small intestine membrane vesicles and doxorubicin cytotoxicity potentiation on K562 cells. The latter assay was performed also on the isomers of 4. The four isomers of each set present different behavior in each of these tests. Compound 3d shows the most promising properties as it was able to completely reverse Pgp-dependent pirarubicin extrusion at low nanomolar concentration, inhibited ATPase activity at 5 x 10(-9) and increased the cytotoxicity of doxorubicin with a reversal fold (RF) of 36.4 at 3 mu M concentration.
• N-BENZYL-3-INDENYLACETAMIDES DERIVATIVES FOR TREATING NEOPLASIA
  申请人：Cell Pathways, Inc.

  公开号：EP1044187A1

  公开（公告）日：2000-10-18
• US3959309A
  申请人：——

  公开号：US3959309A

  公开（公告）日：1976-05-25