(S)-(-)-6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide | 337523-61-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-(-)-6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide
• 英文别名: 6-[(1S)-1-hydroxy-1-(1H-imidazol-5-yl)-2-methylpropyl]-N-methylnaphthalene-2-carboxamide
• CAS: 337523-61-2
• 化学式: C₁₉H₂₁N₃O₂
• 分子量: 323.395
• InChiKey: XEYZCKZMDNQROP-IBGZPJMESA-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：

  (S)-(-)-6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide 、 4-溴苯磺酰氯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以79%的产率得到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-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide 在 Chiralpak AD column 作用下， 以 乙醇 、 正己烷 为溶剂， 以48%的产率得到(S)-(-)-6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-N-methyl-2-naphthamide
  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

文献信息

• 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
• [EN] IMIDAZOL-4-YLMETHANOLS USE AS INHIBITORS OF STEROID C17-20 LYASE<br/>[FR] UTILISATION D'IMIDAZOL-4-YLMETHANOLS EN TANT QU'INHIBITEURS DE LYASE C17-20 STEROIDIENNE
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2001030762A1

  公开（公告）日：2001-05-03

  The present invention provides a compound represented by formula (I), wherein R is a hydrogen atom or a protecting group, R1 is a lower alkyl group or a cyclic alkyl group, R2 is a group represented by formula (1), (wherein a ring A1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents, and a ring A2 and a ring A3 may have substituents), a group represented by formula (2), (wherein the ring B1 is a 5- or 6-membered ring containing an oxygen atom optionally having substituents and a ring B2 and a ring B3 may have substituents) or a group of formula (3), (wherein each of R?3 and R5¿ is a hydrogen atom, a lower alkyl group optionally having substituents, a hydroxyl group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom, R4 is an aromatic hydrocarbon group optionally having substituents, a heterocyclic group optionally having substituents or a carbamoyl group optionally having substituents, R6 is an optionally halogenated lower alkyl group and n is an integer of 0 to 3), or a salt thereof, which has an inhibitory activity of steroid C¿17-20?-lyase and are useful for preventing and treating a mammal suffering from, for example, primary tumor, its metastasis and recurrence thereof, and various symptoms accompanied with these cancer, various diseases such as prostatic hypertrophy, virilism, hirsutism, male pattern alopecia, precocious puberty, endometriosis, uterus myoma, mastopathy, polycystic ovary syndrome, etc.
• 1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4
  作者：Alexander L. Ruchelman、Hon-Wah Man、Roger Chen、Wei Liu、Ling Lu、Dorota Cedzik、Ling Zhang、Jim Leisten、Alice Collette、Rama Krishna Narla、Heather K. Raymon、George W. Muller

  DOI：10.1016/j.bmc.2011.08.068

  日期：2011.11

  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.