methyl 6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthoate | 336102-68-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthoate
• 英文别名: methyl 6-(1-Hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl)-2-naphthoate；rac-Methyl 6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthoate；methyl 6-[1-hydroxy-1-(1H-imidazol-5-yl)-2-methylpropyl]naphthalene-2-carboxylate
• CAS: 336102-68-2
• 化学式: C₁₉H₂₀N₂O₃
• 分子量: 324.379
• InChiKey: RRHVEQWMOKQMRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)propyl]-2-naphthyl trifluoromethanesulfonate 在 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 吡啶盐酸盐 、 三乙胺 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 60.0~70.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 生成 methyl 6-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl]-2-naphthoate
  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 PRODUCING OPTICALLY ACTIVE NAPHTHALENE DERIVATIVE AND OPTICAL RESOLVER THEREFOR
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1227085A1

  公开（公告）日：2002-07-31

  The present invention provides a method of producing an optically active form of a compound represented by the formula (I) having a steroid C17,20-lyase inhibitory activity and is useful as an agent for the prophylaxis or treatment of prostatism, tumor such as breast cancer, and the like or a salt thereof, which method includes reacting a mixture of optically active compounds of a naphthalene derivative represented by the formula: wherein R is a nitrogen-containing heterocyclic group, R1 is a hydrogen atom, a hydrocarbon group or an aromatic heteromonocyclic group, R2 is a hydrogen atom or a lower alkyl group, * shows the position of an asymmetric carbon, R3, R4, R5, R6, R7, R8 and R9 are each independently a hydrogen atom, a hydrocarbon group, a hydroxy group, a thiol group, an amino group, a carbamoyl group, an acyl group or a halogen atom, and R7 is bonded with R6 or R8 to form, together with a carbon atom on a naphthalene ring, a 5 or 6-membered ring containing an oxygen atom, with an optically active form of a compound represented by the formula: wherein ring A is a benzene ring, R10 and R11 are the same or different and each is a hydrogen atom, a hydrocarbon group or a halogen atom, or R10 and R11 in combination show an alkylene group, * shows the position of an asymmetric carbon, and ring B and ring C are each an aromatic ring, separating the resulting salt, and isolating the optically active form, and a novel reagent for optical resolution.

  本发明提供了一种生产由式(I)表示的化合物的光学活性形式的方法，该化合物具有类固醇C17,20-裂解酶抑制活性，可作为预防或治疗前列腺疾病、肿瘤如乳腺癌等的药物或其盐，该方法包括使由式(I)表示的萘衍生物的光学活性化合物混合物反应： 其中 R 是含氮杂环基团，R1 是氢原子、烃基或芳香杂环基团，R2 是氢原子或低级烷基，* 表示不对称碳的位置，R3、R4、R5、R6、R7、R8 和 R9 各自独立地是氢原子、烃基、羟基、硫醇和烷基、羟基、硫醇基、氨基、氨基甲酰基、酰基或卤素原子，R7 与 R6 或 R8 键合，与萘环上的碳原子一起形成含有一个氧原子的 5 或 6 元环，具有以下式子所代表化合物的光学活性形式： 其中，环 A 是苯环，R10 和 R11 相同或不同，且各自是氢原子、烃基或卤原子，或 R10 和 R11 组合显示烯基，* 表示不对称碳的位置，环 B 和环 C 各自是芳香环，分离所得盐，并分离出光学活性形式，以及用于光学解析的新型试剂。
• 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
• US6800778B1
  申请人：——

  公开号：US6800778B1

  公开（公告）日：2004-10-05