6-氨基屈-1,2-二氢二醇 | 117760-93-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 6-氨基屈-1,2-二氢二醇
• 英文名称: trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene
• 英文别名: (+/-)-trans-1,2-dihydroxy-1,2-dihydro-6-aminochrysene；(1S,2S)-6-amino-1,2-dihydrochrysene-1,2-diol
• CAS: 117760-93-7
• 化学式: C₁₈H₁₅NO₂
• 分子量: 277.323
• InChiKey: BDQUGJCOXDENQA-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  66.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  trans-1,2-bis(tert-butyldimethylsilyloxy)-1,2-dihydro-6-aminochrysene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以74 mg的产率得到6-氨基屈-1,2-二氢二醇
  参考文献：
  名称：

  Comparative Tumorigenicity of the Environmental Pollutant 6-Nitrochrysene and Its Metabolites in the Rat Mammary Gland

  摘要：

  Human exposure to the class of nitropolynuclear aromatic hydrocarbons is via inhalation and/or ingestion. Therefore, one of the goals of this study was to determine the propensity of the environmental contaminant 6-nitrochrysene (6-NC) for inducing mammary cancer following its oral administration to female CD rats. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), an established mammary carcinogen in the same animal model, was used as a positive control and trioctanoin as a negative control. Thirty-day-old female CD rats were gavaged once weekly for 8 weeks with 6-NC at 50, 25, or 12.5 mumol/rat or PhIP at 50 mumol/rat in 500 muL of trioctanoin. Twenty-three weeks after the last carcinogen administration, rats were decapitated, necropsied, and evaluated histologically. The most common mammary tumors were adenocarcinomas, followed by adenomas and fibroadenomas. The incidence and multiplicity (mean standard deviation) of mammary adenocarcinomas induced by these two carcinogens at the highest dose (6-NC: 90%, 3.73+/-2.74; PhIP: 83%, 2.62+/-2.58) were significantly higher than those in control rats (10%, 0.10+/-0.31). However, there were no statistically significant differences between groups treated with 6-NC and PhIP or among groups receiving various doses of 6-NC. Following its metabolic activation, 6-NC is known to bind covalently to DNA; however, it remains to be determined whether it can also induce DNA base oxidation. Thus, employing the same route of administration, our studies revealed no effect of 6-NC on the basal level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mammary gland in tests at 6, 24, and 48 h after 6-NC treatment and at termination of the carcinogenesis assay in the normal, noninvolved tissue and in mammary tumors. This result suggests that covalent DNA binding of 6-NC metabolites is important in the induction of mammary cancer in rats. Therefore, the other goal of this study was to compare the tumorigenic activities of 6-NC and its metabolites in the rat mammary gland by intramammary administration. This route has also been used in our laboratory to induce mammary cancer in the rat by 6-NC and is employed here to avoid systemic effects and to determine the role of the mammary gland in the metabolic activation of 6-NC and its metabolites. Toward this end, a new method was developed to obtain ample materials of trans- 1,2-dihydroxy-1,2-dihydro-6-aminochrysene (1,2-DHD-6-AC); other metabolites were synthesized as reported previously. On the basis of the results, the carcinogenic potency toward the mammary gland is ranked in the following order: 6-NC > 1,2-DHD-6-NC > 6-AC > 6-NCDE > 1,2-DHD-6-AC. Among the metabolites tested, 1,2-DHD-6-NC was the most potent carcinogen. It was significantly more active than its reduced product 1,2-DHD-6-AC. However, the potency of 1,2-DHD-6-NC was not significantly different from 6-AC., a metabolite derived from simple nitroreduction, or from 6-NCDE. Collectively, these results suggest that metabolites derived from both ring-oxidation and nitroreduction contribute to the overall carcinogenicity of 6-NC in the rat mammary gland.

  DOI：

  10.1021/tx020019a

文献信息

• FMO3 inhibitors for treating pain
  申请人：Akron Molecules GmbH

  公开号：EP2674161A1

  公开（公告）日：2013-12-18

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.

  本发明涉及治疗疼痛和相关疾病的新疗法，以及用于上述疗法的药物化合物。
• Compounds and Methods for Treating Pain
  申请人：Penninger Josef

  公开号：US20130252924A1

  公开（公告）日：2013-09-26

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.
• COMPOUNDS AND METHODS FOR TREATING PAIN
  申请人：AKRON MOLECULES AG

  公开号：US20140349969A1

  公开（公告）日：2014-11-27

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.
• Comparative Tumorigenicity of the Environmental Pollutant 6-Nitrochrysene and Its Metabolites in the Rat Mammary Gland
  作者：Karam El-Bayoumy、Dhimant Desai、Telih Boyiri、Jose Rosa、Jacek Krzeminski、Arun K. Sharma、Brian Pittman、Shantu Amin

  DOI：10.1021/tx020019a

  日期：2002.7.1

  Human exposure to the class of nitropolynuclear aromatic hydrocarbons is via inhalation and/or ingestion. Therefore, one of the goals of this study was to determine the propensity of the environmental contaminant 6-nitrochrysene (6-NC) for inducing mammary cancer following its oral administration to female CD rats. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), an established mammary carcinogen in the same animal model, was used as a positive control and trioctanoin as a negative control. Thirty-day-old female CD rats were gavaged once weekly for 8 weeks with 6-NC at 50, 25, or 12.5 mumol/rat or PhIP at 50 mumol/rat in 500 muL of trioctanoin. Twenty-three weeks after the last carcinogen administration, rats were decapitated, necropsied, and evaluated histologically. The most common mammary tumors were adenocarcinomas, followed by adenomas and fibroadenomas. The incidence and multiplicity (mean standard deviation) of mammary adenocarcinomas induced by these two carcinogens at the highest dose (6-NC: 90%, 3.73+/-2.74; PhIP: 83%, 2.62+/-2.58) were significantly higher than those in control rats (10%, 0.10+/-0.31). However, there were no statistically significant differences between groups treated with 6-NC and PhIP or among groups receiving various doses of 6-NC. Following its metabolic activation, 6-NC is known to bind covalently to DNA; however, it remains to be determined whether it can also induce DNA base oxidation. Thus, employing the same route of administration, our studies revealed no effect of 6-NC on the basal level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mammary gland in tests at 6, 24, and 48 h after 6-NC treatment and at termination of the carcinogenesis assay in the normal, noninvolved tissue and in mammary tumors. This result suggests that covalent DNA binding of 6-NC metabolites is important in the induction of mammary cancer in rats. Therefore, the other goal of this study was to compare the tumorigenic activities of 6-NC and its metabolites in the rat mammary gland by intramammary administration. This route has also been used in our laboratory to induce mammary cancer in the rat by 6-NC and is employed here to avoid systemic effects and to determine the role of the mammary gland in the metabolic activation of 6-NC and its metabolites. Toward this end, a new method was developed to obtain ample materials of trans- 1,2-dihydroxy-1,2-dihydro-6-aminochrysene (1,2-DHD-6-AC); other metabolites were synthesized as reported previously. On the basis of the results, the carcinogenic potency toward the mammary gland is ranked in the following order: 6-NC > 1,2-DHD-6-NC > 6-AC > 6-NCDE > 1,2-DHD-6-AC. Among the metabolites tested, 1,2-DHD-6-NC was the most potent carcinogen. It was significantly more active than its reduced product 1,2-DHD-6-AC. However, the potency of 1,2-DHD-6-NC was not significantly different from 6-AC., a metabolite derived from simple nitroreduction, or from 6-NCDE. Collectively, these results suggest that metabolites derived from both ring-oxidation and nitroreduction contribute to the overall carcinogenicity of 6-NC in the rat mammary gland.