4-[3-(4-amino-3-methylphenyl)pentan-3-yl]-2-methylphenol | 863408-16-6

• 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: 4-[3-(4-amino-3-methylphenyl)pentan-3-yl]-2-methylphenol
• 英文别名: 4-[3-(4-Amino-3-methylphenyl)pentan-3-yl]-2-methylphenol
• CAS: 863408-16-6
• 化学式: C₁₉H₂₅NO
• 分子量: 283.414
• InChiKey: VPXDZYWOCIIVMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-[3-(4-amino-3-methylphenyl)pentan-3-yl]-2-methylphenol 在 sodium tetrahydroborate 、 三乙胺 、 cesium fluoride 、 potassium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (R,S)-DPP-1023
  参考文献：
  名称：

  Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors: Dual activities and metabolic activation

  摘要：

  Ligands possessing dual vitamin D-3 (VD3)-agonistic and androgen-antagonistic activities with various activity spectra were prepared based on a substituted 3,3-diphenylpentane (DPP) skeleton. Among the compounds, (R,S)-DPP-1023 [(R,S)-7b] and (S,S)-DPP-0123 [(S,S)-7c] showed the most potent vitamin D-3-agonistic activity [with potency comparable to that of 1 alpha,25-dihydroxyvitamin D-3 (1,25-VD3)] and nuclear androgen receptor (AR)-binding activity (with higher affinity than that of hydroxyflutamide), respectively. Metabolic activation (reduction of the carbonyl group) of pivaloyl analogs [DPP- 1113 (3a), DPP- 10 13 (3b), DPP-0113 (3c), and DPP-0013 (3d)] in HL-60 cells was found to be necessary for binding to nuclear vitamin D-3 receptor (VDR). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.04.039
• 作为产物：
  描述：

  邻甲酚 在 甲烷磺酸 作用下， 反应 75.0h， 生成 4-[3-(4-amino-3-methylphenyl)pentan-3-yl]-2-methylphenol
  参考文献：
  名称：

  3,3-Diphenylpentane skeleton as a steroid skeleton substitute: Novel inhibitors of human 5α-reductase 1

  摘要：

  We designed and synthesized novel type 1 5 alpha-reductase inhibitors by using 3,3-diphenylpentane skeleton as a substitute for the usual steroid skeleton. 4-(3-(4-(N-Methylacetamido)phenyl)pentan-3-yl)phenyl dibenzylcarbamate (11k) is a competitive 5 alpha-reductase inhibitor with the IC50 value of 0.84 mu M. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.039

文献信息

• Structure–activity relationships of bisphenol A analogs at estrogen receptors (ERs): Discovery of an ERα-selective antagonist
  作者：Keisuke Maruyama、Masaharu Nakamura、Shusuke Tomoshige、Kazuyuki Sugita、Makoto Makishima、Yuichi Hashimoto、Minoru Ishikawa

  DOI：10.1016/j.bmcl.2013.05.067

  日期：2013.7

  Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ER alpha/ER beta subtype selectivity. Among the compounds examined, 18 was found to be a potent ER alpha-antagonist with high selectivity over ER beta and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ER alpha. ER alpha-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. (C) 2013 Elsevier Ltd. All rights reserved.
• Ligands with dual vitamin D3-agonistic and androgen-antagonistic activities
  作者：Shinnosuke Hosoda、Aya Tanatani、Ken-ichi Wakabayashi、Yusuke Nakano、Hiroyuki Miyachi、Kazuo Nagasawa、Yuichi Hashimoto

  DOI：10.1016/j.bmcl.2005.06.044

  日期：2005.10

  Ligands possessing dual vitamin D-3-agonistic (estimated as HL-60 monocytic cell differentiation induction) and androgen-antagonistic (estimated as testosterone-induced SC-3 cell growth inhibition) activities with various activity spectra were prepared based on a substituted bis-phenylmethane skeleton. Some of them were revealed to be potent androgen antagonists with a nonsecosteroidal vitamin D-3 skeleton. (c) 2005 Elsevier Ltd. All rights reserved.
• Diphenylmethane skeleton as a multi-template for nuclear receptor ligands: Preparation of FXR and PPAR ligands
  作者：Masahiko Kainuma、Jun-ichi Kasuga、Shinnosuke Hosoda、Ken-ichi Wakabayashi、Aya Tanatani、Kazuo Nagasawa、Hiroyuki Miyachi、Makoto Makishima、Yuichi Hashimoto

  DOI：10.1016/j.bmcl.2006.03.075

  日期：2006.6

  Novel, potent farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists were obtained by using a diphenylmethane skeleton as a substitute for a steroid skeleton. (c) 2006 Elsevier Ltd. All rights reserved.
• 3,3-Diphenylpentane skeleton as a steroid skeleton substitute: Novel inhibitors of human 5α-reductase 1
  作者：Shinnosuke Hosoda、Yuichi Hashimoto

  DOI：10.1016/j.bmcl.2007.07.039

  日期：2007.10

  We designed and synthesized novel type 1 5 alpha-reductase inhibitors by using 3,3-diphenylpentane skeleton as a substitute for the usual steroid skeleton. 4-(3-(4-(N-Methylacetamido)phenyl)pentan-3-yl)phenyl dibenzylcarbamate (11k) is a competitive 5 alpha-reductase inhibitor with the IC50 value of 0.84 mu M. (C) 2007 Elsevier Ltd. All rights reserved.
• Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors: Dual activities and metabolic activation
  作者：Shinnosuke Hosoda、Aya Tanatani、Ken-ichi Wakabayashi、Makoto Makishima、Keisuke Imai、Hiroyuki Miyachi、Kazuo Nagasawa、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2006.04.039

  日期：2006.8

  Ligands possessing dual vitamin D-3 (VD3)-agonistic and androgen-antagonistic activities with various activity spectra were prepared based on a substituted 3,3-diphenylpentane (DPP) skeleton. Among the compounds, (R,S)-DPP-1023 [(R,S)-7b] and (S,S)-DPP-0123 [(S,S)-7c] showed the most potent vitamin D-3-agonistic activity [with potency comparable to that of 1 alpha,25-dihydroxyvitamin D-3 (1,25-VD3)] and nuclear androgen receptor (AR)-binding activity (with higher affinity than that of hydroxyflutamide), respectively. Metabolic activation (reduction of the carbonyl group) of pivaloyl analogs [DPP- 1113 (3a), DPP- 10 13 (3b), DPP-0113 (3c), and DPP-0013 (3d)] in HL-60 cells was found to be necessary for binding to nuclear vitamin D-3 receptor (VDR). (c) 2006 Elsevier Ltd. All rights reserved.