[3-(quinolin-2-yl)phenyl]methanol | 1349717-39-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [3-(quinolin-2-yl)phenyl]methanol
• 英文别名: (3-(Quinolin-2-yl)phenyl)methanol；(3-quinolin-2-ylphenyl)methanol
• CAS: 1349717-39-0
• 化学式: C₁₆H₁₃NO
• 分子量: 235.285
• InChiKey: QBGLSCNAKZEZFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-ol 、 [3-(quinolin-2-yl)phenyl]methanol 在 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 以54%的产率得到2-[3-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}-methyl)phenyl]quinoline dihydrochloride
  参考文献：
  名称：

  Synthesis and <i>in Vivo</i> Evaluation of Novel Quinoline Derivatives as Phosphodiesterase 10A Inhibitors

  摘要：

  从2-({4-[1-甲基-4-(吡啶-4-基)-1H-吡唑-3-基]苯氧基}甲基)喹啉（MP-10）出发，设计并合成了一类新型的磷酸二酯酶10A（PDE10A）抑制剂，其在小鼠肝微粒体中具有改善的代谢稳定性。将MP-10的苯氧甲基部分替换为氧甲基苯单元后，鉴定出2-[4-({[1-甲基-4-(吡啶-4-基)-1H-吡唑-3-基]氧}甲基)苯基]喹啉（14），该化合物在小鼠和人肝微粒体中显示出中等的PDE10A抑制活性，且代谢稳定性优于MP-10。化合物14在腹腔注射后在血浆和脑中显示出高浓度，并剂量依赖性地减轻了苯环利定引起的小鼠过度运动，口服给药14（0.1, 0.3 mg/kg）也能改善小鼠的视觉识别记忆障碍。

  DOI：

  10.1248/cpb.c14-00509
• 作为产物：
  描述：

  2-氯喹啉 、 3-羟甲基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 14.0h， 以100%的产率得到[3-(quinolin-2-yl)phenyl]methanol
  参考文献：
  名称：

  Synthesis and <i>in Vivo</i> Evaluation of Novel Quinoline Derivatives as Phosphodiesterase 10A Inhibitors

  摘要：

  从2-({4-[1-甲基-4-(吡啶-4-基)-1H-吡唑-3-基]苯氧基}甲基)喹啉（MP-10）出发，设计并合成了一类新型的磷酸二酯酶10A（PDE10A）抑制剂，其在小鼠肝微粒体中具有改善的代谢稳定性。将MP-10的苯氧甲基部分替换为氧甲基苯单元后，鉴定出2-[4-({[1-甲基-4-(吡啶-4-基)-1H-吡唑-3-基]氧}甲基)苯基]喹啉（14），该化合物在小鼠和人肝微粒体中显示出中等的PDE10A抑制活性，且代谢稳定性优于MP-10。化合物14在腹腔注射后在血浆和脑中显示出高浓度，并剂量依赖性地减轻了苯环利定引起的小鼠过度运动，口服给药14（0.1, 0.3 mg/kg）也能改善小鼠的视觉识别记忆障碍。

  DOI：

  10.1248/cpb.c14-00509

文献信息

• Human androgen receptor DNA-binding domain (DBD) compounds as therapeutics and methods for their use
  申请人：The University of British Columbia

  公开号：US10011573B2

  公开（公告）日：2018-07-03

  A compound having the structure of Formula I, wherein A is a substituted or unsubstituted aryl or heteroaryl group, D is a substituted or unsubstituted 5- or 6-membered heteroaryl or heterocyclyl group and E is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl or heterocyclyl group. The compounds are used for the treatment of androgen modulated indications including cancer (prostate, breast, ovarian, endometrial or bladder cancer), hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age related macular degeneration. The use of the compounds for the manufacture of a medicament for modulating AR activity, a method of treatment using such compounds and a pharmaceutical composition and a commercial package comprising said compounds are also described.

  具有式 I 结构的化合物，其中 A 是取代或未取代的芳基或杂芳基，D 是取代或未取代的 5 或 6 元杂芳基或杂环基，E 是取代或未取代的芳基、杂芳基、环烷基或杂环基。这些化合物可用于治疗雄激素调节适应症，包括癌症（前列腺癌、乳腺癌、卵巢癌、子宫内膜癌或膀胱癌）、脱发、痤疮、多毛症、卵巢囊肿、多囊卵巢病、性早熟和老年性黄斑变性。此外，还描述了这些化合物在制造调节 AR 活性的药物中的用途、使用这些化合物的治疗方法以及包含上述化合物的药物组合物和商业包装。
• HUMAN ANDROGEN RECEPTOR DNA-BINDING DOMAN (DBD) COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE
  申请人：The University of British Columbia

  公开号：US20170183319A1

  公开（公告）日：2017-06-29

  A compound having the structure of Formula I, wherein A is a substituted or unsubstituted aryl or heteroaryl group, D is a substituted or unsubstituted 5- or 6-membered heteroaryl or heterocyclyl group and E is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl or heterocyclyl group. The compounds are used for the treatment of androgen modulated indications including cancer (prostate, breast, ovarian, endometrial or blader cancer), hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age related macular degeneration. The use of the compounds for the manufacture of a medicament for modulating AR activity, a method of treatment using such compounds and a pharmaceutical composition and a commercial package comprising said compounds arc also described.
• Synthesis and &lt;i&gt;in Vivo&lt;/i&gt; Evaluation of Novel Quinoline Derivatives as Phosphodiesterase 10A Inhibitors
  作者：Wataru Hamaguchi、Naoyuki Masuda、Kiyohiro Samizu、Takuma Mihara、Kaori Takama、Toshihiro Watanabe

  DOI：10.1248/cpb.c14-00509

  日期：——

  A novel class of phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability in mouse liver microsomes were designed and synthesized starting from 2-(4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline (MP-10). Replacement of the phenoxymethyl part of MP-10 with an oxymethyl phenyl unit led to the identification of 2-[4-([1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (14), which showed moderate PDE10A inhibitory activity with improved metabolic stability in mouse and human liver microsomes over MP-10. Compound 14 showed high concentrations in plasma and brain after intraperitoneal administration and dose-dependently attenuated the hyperlocomotion induced by phencyclidine in mice, and oral administration of 14 (0.1, 0.3 mg/kg) also improved visual-recognition memory impairment in mice.

  从2-(4-[1-甲基-4-(吡啶-4-基)-1H-吡唑-3-基]苯氧基}甲基)喹啉（MP-10）出发，设计并合成了一类新型的磷酸二酯酶10A（PDE10A）抑制剂，其在小鼠肝微粒体中具有改善的代谢稳定性。将MP-10的苯氧甲基部分替换为氧甲基苯单元后，鉴定出2-[4-([1-甲基-4-(吡啶-4-基)-1H-吡唑-3-基]氧}甲基)苯基]喹啉（14），该化合物在小鼠和人肝微粒体中显示出中等的PDE10A抑制活性，且代谢稳定性优于MP-10。化合物14在腹腔注射后在血浆和脑中显示出高浓度，并剂量依赖性地减轻了苯环利定引起的小鼠过度运动，口服给药14（0.1, 0.3 mg/kg）也能改善小鼠的视觉识别记忆障碍。