2,2,4,4,5,7-hexamethyl-6-hydroxy-3,4-dihydro-2H-benzo[b]pyran | 203856-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2,2,4,4,5,7-hexamethyl-6-hydroxy-3,4-dihydro-2H-benzo[b]pyran
• 英文别名: 2,2,4,4,5,7-hexamethyl-3H-chromen-6-ol
• CAS: 203856-52-4
• 化学式: C₁₅H₂₂O₂
• 分子量: 234.338
• InChiKey: MTUVLOPQYKXBLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  对苯二甲酸单甲酯 、 2,2,4,4,5,7-hexamethyl-6-hydroxy-3,4-dihydro-2H-benzo[b]pyran 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以52%的产率得到Terephthalic acid 1-(2,2,4,4,5,7-hexamethyl-chroman-6-yl) ester 4-methyl ester
  参考文献：
  名称：

  Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors

  摘要：

  A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu / nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RAR alpha, RXR alpha, and RXR beta were similar in the two cell lines, while RAR beta expression was higher in SCC-2 over SCC-38, and RAR gamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

  DOI：

  10.1021/jm990292i
• 作为产物：
  描述：

  6-hydroxy-4,4,5,7-tetramethylbenzopyran-2-one 在 4-二甲氨基吡啶 、 4 A molecular sieve 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 170.0h， 生成 2,2,4,4,5,7-hexamethyl-6-hydroxy-3,4-dihydro-2H-benzo[b]pyran
  参考文献：
  名称：

  Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors

  摘要：

  A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu / nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RAR alpha, RXR alpha, and RXR beta were similar in the two cell lines, while RAR beta expression was higher in SCC-2 over SCC-38, and RAR gamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

  DOI：

  10.1021/jm990292i

文献信息

• [EN] HETEROAROTINOIDS-ANTICANCER AGENTS WITH RECEPTOR SPECIFICITY AND TGASE ACTIVITY<br/>[FR] AGENTS ANTICANCEREUX HETERO-AROTINOIDES POSSEDANT UNE SPECIFICITE EN MATIERE DE RECEPTEURS ET UNE ACTIVITE DE TGASE
  申请人：——

  公开号：WO1998007716A2

  公开（公告）日：1998-02-26

  [EN] Anticancer compositions having receptor specificity as well as activity in stimulating formation of the enzyme transglutaminase as a marker for anticancer activity. The compositions comprise certain heteroarotinoid structures partially related to trans-retinoic acid through the basic, fused-ring framework.
  [FR] Compositions anticancéreuses ayant une spécificité en matière de récepteurs et manifestant une activité qui stimule la formation de l'enzyme transglutaminase servant de marqueur dans l'activité anticancéreuse. Les compositions comprennent certaines structures hétéro-arotinoïdes partiellement liées à l'acide transrétinoïque par le réseau de base à anneaux condensés.
• Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors
  作者：David Zacheis、Arindam Dhar、Shennan Lu、Matora M. Madler、Jozef Klucik、Chad W. Brown、Shengquan Liu、Francis Clement、Shankar Subramanian、G. Mahika Weerasekare、K. Darrell Berlin、Michael A. Gold、John R. Houck,、Kenneth R. Fountain、Doris M. Benbrook

  DOI：10.1021/jm990292i

  日期：1999.10.1

  A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu / nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RAR alpha, RXR alpha, and RXR beta were similar in the two cell lines, while RAR beta expression was higher in SCC-2 over SCC-38, and RAR gamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.