N-(3,4-dimethoxyphenyl)-5-methoxy-2,2-dimethyl-2H-chromene-6-carboxamide

• 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: N-(3,4-dimethoxyphenyl)-5-methoxy-2,2-dimethyl-2H-chromene-6-carboxamide
• 英文别名: N-(3,4-dimethoxyphenyl)-5-methoxy-2,2-dimethyl-2h-chromene-6-carboxamide；N-(3,4-dimethoxyphenyl)-5-methoxy-2,2-dimethylchromene-6-carboxamide
• 化学式: C₂₁H₂₃NO₅
• 分子量: 369.417
• InChiKey: IFJBQEBQNMXRBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,4-dimethoxyphenyl)-5-methoxy-2,2-dimethyl-2H-chromene-6-carboxamide 在 叠氮磷酸二苯酯 、 四丁基氟化铵 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成
  参考文献：
  名称：

  Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

  摘要：

  On the basis of deguelin, a series of the B, C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1 alpha inhibition. Among them, compound 57 showed potent HIF-1 alpha inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 Cterminal inhibitor.

  DOI：

  10.1016/j.bmc.2019.02.040
• 作为产物：
  描述：

  5-methoxy-2,2-dimethyl-2H-chromene-6-carbaldehyde 在 sodium chlorite 、 双氧水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 20.0h， 生成 N-(3,4-dimethoxyphenyl)-5-methoxy-2,2-dimethyl-2H-chromene-6-carboxamide
  参考文献：
  名称：

  Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

  摘要：

  On the basis of deguelin, a series of the B, C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1 alpha inhibition. Among them, compound 57 showed potent HIF-1 alpha inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 Cterminal inhibitor.

  DOI：

  10.1016/j.bmc.2019.02.040

文献信息

• Discovery of deguelin derivatives in combination with fluconazole against drug-resistant Candida albicans
  作者：Biaoqi Liu、Youwei Wu、Dingmei Qin、Hairong Wang、Hongjie Chen、Yi Zhang、Weilie Xiao、Xiaoli Li、Ruirui Wang、Ruihan Zhang

  DOI：10.1007/s00044-023-03118-7

  日期：2023.10

  promising therapeutic strategy. In this study, a series of deguelin (Deg) derivative were prepared and identified with in vitro antifungal activity against drug-resistant C. albicans combined with fluconazole (FLC). The combination of Deg derivative 17c and FLC exhibited the best activity, with a fractional inhibitory combination index (FICI) of 0.02. The sensitization effect of 17c + FLC was further

  白色念珠菌作为最常见的条件致病菌，给临床治疗带来了很大的困难。与此同时，随着唑类药物在临床实践中的广泛应用，耐药性也随之出现。在这种情况下，采用联合治疗就成为一种有前景的治疗策略。本研究制备了一系列德桂林（Deg）衍生物，并鉴定其与氟康唑（FLC）联用对耐药白色念珠菌具有体外抗真菌活性。Deg衍生物17c和FLC的组合表现出最好的活性，其抑制组合指数(FICI)为0.02。 通过时间杀菌曲线分析进一步验证了17c +FLC的致敏效果。此外，17c + FLC 还对耐药白色念珠菌 的菌丝转化和生物膜形成具有抑制作用，并显着降低与 RAS1/cAMP/PKA 细胞转导途径相关的关键基因的表达。
• Novel Hypoxia-Inducible Factor 1α (HIF-1α) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy
  作者：Hongchan An、Seungbeom Lee、Jung Min Lee、Dong Hyun Jo、Joohwan Kim、Yoo-Seong Jeong、Mi Jeong Heo、Chang Sik Cho、Hoon Choi、Ji Hae Seo、Seyeon Hwang、Jihye Lim、Taewoo Kim、Hyoung Oh Jun、Jaehoon Sim、Changjin Lim、Joonseong Hur、Jungmin Ahn、Hyun Su Kim、Seung-Yong Seo、Younghwa Na、Seok-Ho Kim、Jeewoo Lee、Jeeyeon Lee、Suk-Jae Chung、Young-Myeong Kim、Kyu-Won Kim、Sang Geon Kim、Jeong Hun Kim、Young-Ger Suh

  DOI：10.1021/acs.jmedchem.8b00971

  日期：2018.10.25

  Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring.