5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-nitro-2-naphthylamine | 155877-70-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-nitro-2-naphthylamine
• 英文别名: 5,5,8,8-Tetramethyl-3-nitro-6,7-dihydronaphthalen-2-amine
• CAS: 155877-70-6
• 化学式: C₁₄H₂₀N₂O₂
• 分子量: 248.325
• InChiKey: RXGHMZJAWXGTDI-UHFFFAOYSA-N

物化性质

• 沸点：
  372.7±42.0 °C(Predicted)
• 密度：
  1.092±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-nitro-2-naphthylamine 在 盐酸 、 铁粉 、 sodium hydride 作用下， 以 xylene 为溶剂， 反应 3.5h， 生成 methyl 4-(1H-2,3,7,8,9,10-hexahydro-1,7,7,10,10-pentamethyl-2-oxonaphtho<2,3-b><1,4>diazepin-4-yl)benzoate
  参考文献：
  名称：

  Retinobenzoic Acids. 6. Retinoid Antagonists with a Heterocyclic Ring

  摘要：

  Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzimidazole derivative, 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnapth[2,3-d]imidazol-2-yl)benzoic acid (7a), and related compounds with a small alkyl group instead of the hydrogen on the nitrogen (N-1) atom of the imidazole ring exhibited retinoidal activity, and the potency strongly depended on the bulkiness of the substituent. The compounds having a phenyl or benzyl group on the nitrogen lacked differentiation-inducing activity on HL-60 cells and acted as antagonists to the potent retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)carbamoyl]benzoic acid (Am80). Among the compounds possessing a seven-membered heterocyclic ring as a linking group, 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10-pentamethylbenzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid (16) also exhibited the antagonistic activity. The binding abilities of these compounds to retinoic acid receptors ct and P were consistent with their potency for the inhibition of HL-60 cell differentiation induced by the retinoid Am80.

  DOI：

  10.1021/jm00036a017
• 作为产物：
  描述：

  N-(5,5,8,8-四甲基-5,6,7,8-四氢-2-萘)乙酰胺 (他米巴罗汀) 在 sodium hydroxide 、 三氟甲磺酸 、 potassium nitrate 作用下， 以 乙醇 为溶剂， 反应 3.5h， 生成 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-nitro-2-naphthylamine
  参考文献：
  名称：

  Retinobenzoic Acids. 6. Retinoid Antagonists with a Heterocyclic Ring

  摘要：

  Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzimidazole derivative, 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnapth[2,3-d]imidazol-2-yl)benzoic acid (7a), and related compounds with a small alkyl group instead of the hydrogen on the nitrogen (N-1) atom of the imidazole ring exhibited retinoidal activity, and the potency strongly depended on the bulkiness of the substituent. The compounds having a phenyl or benzyl group on the nitrogen lacked differentiation-inducing activity on HL-60 cells and acted as antagonists to the potent retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)carbamoyl]benzoic acid (Am80). Among the compounds possessing a seven-membered heterocyclic ring as a linking group, 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10-pentamethylbenzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid (16) also exhibited the antagonistic activity. The binding abilities of these compounds to retinoic acid receptors ct and P were consistent with their potency for the inhibition of HL-60 cell differentiation induced by the retinoid Am80.

  DOI：

  10.1021/jm00036a017

文献信息

• Regulation of Retinoidal Actions by Diazepinylbenzoic Acids. Retinoid Synergists Which Activate the RXR−RAR Heterodimers
  作者：Hiroki Umemiya、Hiroshi Fukasawa、Masayuki Ebisawa、Laurence Eyrolles、Emiko Kawachi、Ghislaine Eisenmann、Hinrich Gronemeyer、Yuichi Hashimoto、Koichi Shudo、Hiroyuki Kagechika

  DOI：10.1021/jm9704309

  日期：1997.12.1

  15-pentamethyldinaphtho[2,3-b][1,2-e]diazepin-7-yl) benzoic acid (LE540, 17), exhibits a 1 order of magnitude higher antagonistic potential than the parental LE135 (6). In contrast, 4-[5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyldibenzo[b,e] [1,4]diazepin-11-yl]-benzoic acid (HX600, 7), a structural isomer of the antagonistic LE135 (6), enhanced HL-60 cell differentiation induced by RAR agonists, such as Am80 (2)

  在人HL-60早幼粒细胞白血病细胞中，二氮杂pin基苯甲酸衍生物可以对天然或合成类维生素A的诱导分化活性表现出拮抗或协同作用，该活性很大程度上取决于二氮杂ring环上取代基的性质。因此，类视黄醇拮抗剂LE135（6），4-（13H-10,11,12,13-tetRAhydro-10，10,13,13,15-五甲基二萘并[2,3-b] [1,2 -e] diazepin-7-yl）苯甲酸（LE540，17）的拮抗潜力比亲代LE135（6）高1个数量级。相反，4- [5H-2,3-（2,5-二甲基-2,5-己基）-5-甲基二苯并[b，e] [1,4]二氮杂-11-基]-苯甲酸（HX600 ，LEAF（6）的结构异构体，（7）增强了RAR激动剂（例如Am80）诱导的HL-60细胞分化（2）。噻嗪类化合物HX630（29）和氮杂类衍生物HX640（30）的协同作用进一步增强。两者都比HX600（7
• Design and Synthesis of Novel Retinoid Synergists Having a Dibenzodiazepine Skeleton
  作者：Hiroyuki Kagechika、Kiminori Ohta、Emiko Kawachi、Koichi Shudo

  DOI：10.3987/com-10-12046

  日期：——

  Based on the structures of potent RXR agonists 2 and 3, novel dibenzodiazepine derivatives 4 - 6, containing two diphenylamine substructures, were designed as RXR modulator candidates and synthesized by utilizing Pd-catalyzed and Cu-promoted diphenylamine-generating reactions as key reactions. These compounds showed retinoid-synergistic activity, enhancing the HL-60 cell differentiation-inducing ability of the RAR agonist Am80.