6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide | 337521-84-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide
• 英文别名: 6-(1-Hydroxy-1-(1H-imidazol-4-yl)-2-methyl-propyl)-N-methyl-2-naphthamide；6-[1-hydroxy-1-(1H-imidazol-5-yl)-2-methylpropyl]-N-methylnaphthalene-2-carboxamide
• CAS: 337521-84-3
• 化学式: C₁₉H₂₁N₃O₂
• 分子量: 323.395
• InChiKey: XEYZCKZMDNQROP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  78
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide 在 三乙胺 作用下， 以 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 6-[(1S)-1-(1-[(4-bromophenyl)sulfonyl]-1H-imidazol-4-yl)-1-hydroxy-2-methylpropyl]-N-methylnaphthalene-2-carboxamide
  参考文献：
  名称：

  1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4

  摘要：

  A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50) = 54 nM) and antitubulin activity (HCT-116 IC(50) = 34 nM and tubulin polymerization IC(50) similar to 1 mu M). While the nitrile group at the alkene terminus was generally required for potent antiproliferative activity, its replacement was tolerated if there was a hydroxyl or amino group on one of the aryl rings. Conveniently, this group could also serve as a handle for amino acid derivatization to improve the compounds' solubility. The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.068
• 作为产物：
  描述：

  6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-2-naphthyl trifluoromethanesulfonate 在 甲醇 、 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 吡啶盐酸盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 28.0h， 生成 6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide
  参考文献：
  名称：

  17,20-Lyase inhibitors. Part 4: Design, synthesis and structure–activity relationships of naphthylmethylimidazole derivatives as novel 17,20-lyase inhibitors

  摘要：

  A novel series of naphthylmethylimidazole derivatives and related compounds have been investigated as selective 17,20-lyase inhibitors. Optimization of the substituent at the 6-position on the naphthalene ring was performed to yield a methylcarbamoyl derivative, which exhibited potent inhibitory activity against human 17,20-lyase and promising selectivity (> 200-fold) for 17,20-lyase over CYP3A4. Further modifications of the methylcarbamoyl derivative led to the discovery of the corresponding tricyclic compound, which showed highly potent activity against human 17,20-lyase (IC50 19 nM) and good selectivity (> 1000-fold) for inhibition of 17,20-lyase over CYP3A4. Additional biological evaluation revealed that the tricyclic compound had potent in vivo efficacy in monkeys and favorable pharmacokinetic profiles when administered in rats. Asymmetric synthesis of the selective tricyclic inhibitor was also achieved using a chiral alpha-hydroxy ketone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.017

文献信息

• Imidazol-4-ylmehanols and their use as inhibitors of steroid C17-20 lyase
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06649643B1

  公开（公告）日：2003-11-18

  Imidazol-4-ylmethanols and their uses for preventing and treating primary tumors, metastasis and recurrence of tumors, various symptoms accompanying tumors, prostatic hypertrophy, virilism, hirsutism, male pattern alopecia, precocious puberty, endometriosis, uterine myoma, mastopathy and polycystic ovary syndrome are disclosed.

  Imidazol-4-ylmethanols及其用于预防和治疗原发性肿瘤、肿瘤转移和复发、伴随肿瘤的各种症状、前列腺肥大、男性化、多毛症、男性型脱发、性早熟、子宫内膜异位症、子宫肌瘤、乳腺病和多囊卵巢综合征的用途被披露。
• PROCESS FOR THE PREPARATION OF IMIDAZOLE DERIVATIVES
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1193258A1

  公开（公告）日：2002-04-03

  The present invention provides an industrially advantageous production method of compound (V) having a steroid C17,20 lyase inhibitory action, which affords this compound in a high yield with a less number of steps without using a heavy metal compound: wherein ring A is an optionally substituted imidazole ring, R is an optionally substituted hydrocarbon group or a heterocyclic group, and R1, R2, R3, R4, R5, R6 and R7 are each a hydrogen atom, an optionally substituted hydrocarbon group, OH, SH or NH2, an acyl group or a halogen and the like.

  本发明提供了一种在不使用重金属化合物的情况下，以较少的步骤高产率地制备具有类固醇C17,20裂解酶抑制作用的化合物（V）的工业上有利的生产方法：其中环A是一个可选择取代的咪唑环，R是一个可选择取代的碳氢化合物基团或杂环基团，R1、R2、R3、R4、R5、R6和R7分别是氢原子、可选择取代的碳氢化合物基团、羟基、硫氢基或氨基、酰基或卤素等。
• IMIDAZOL-4-YLMETHANOLS USED AS INHIBITORS OF STEROID C17-20 LYASE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1222174B1

  公开（公告）日：2009-05-27
• US6649643B1
  申请人：——

  公开号：US6649643B1

  公开（公告）日：2003-11-18
• US6713632B1
  申请人：——

  公开号：US6713632B1

  公开（公告）日：2004-03-30