1-(2-羟基-6-三氟甲基苯基)乙酮 | 1024605-96-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(2-羟基-6-三氟甲基苯基)乙酮
• 英文名称: 1-(2-hydoxy-6-trifluoromethylphenyl)ethanone
• 英文别名: 1-(2-hydroxy-6-trifluoromethylphenyl)ethanone；1-(2-Hydroxy-6-trifluoromethylphenyl)ethanone；1-[2-hydroxy-6-(trifluoromethyl)phenyl]ethanone
• CAS: 1024605-96-6
• 化学式: C₉H₇F₃O₂
• 分子量: 204.149
• InChiKey: ZKQUZJANRPHHHK-UHFFFAOYSA-N

物化性质

• 沸点：
  244.5±40.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-羟基-6-三氟甲基苯基)乙酮 、 N-叔丁氧羰基-4-哌啶酮 在 四氢吡咯 作用下， 以 丙醇 为溶剂， 反应 19.5h， 以70%的产率得到4-oxo-5-trifluoromethyl-3,4-dihydro-1'H-spiro(chromene-2,4'-piperidine)-1'-carboxylate
  参考文献：
  名称：

  Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] analogs

  摘要：

  In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID(50) = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC(50) (mouse)= 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg). (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.044
• 作为产物：
  描述：

  2-羟基-6-三氟甲基苯甲酸甲酯 、 甲基溴化镁 在 三乙胺 作用下， 以 乙醚 、 甲苯 为溶剂， 以55%的产率得到1-(2-羟基-6-三氟甲基苯基)乙酮
  参考文献：
  名称：

  Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]

  摘要：

  Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.043

文献信息

• Novel Oxime Derivatives and Their Use As Allosteric Modulators of Metabotropic Glutamate Receptors
  申请人：Schann Stephan

  公开号：US20120277212A1

  公开（公告）日：2012-11-01

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

  本发明提供了一般式（I）的新的肟衍生物，以及包含它们的制药组合物，以及它们用于治疗和/或预防与改变谷氨酸信号和/或功能相关的疾病和/或与哺乳动物中谷氨酸水平或信号改变有关的疾病的用途。本发明还提供了一般式（I）的新的肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新的肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向异构调节剂，更具体地说是mGluR4的正向异构调节剂。
• Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] analogs
  作者：Yoshikazu Uto、Yuko Ueno、Yohei Kiyotsuka、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Makiko Yamada、Tsuneo Deguchi、Masahiro Konishi、Toshiyuki Takagi、Satoko Wakimoto、Jun Ohsumi

  DOI：10.1016/j.ejmech.2010.07.044

  日期：2010.11

  In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1'-6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID(50) = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC(50) (mouse)= 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg). (C) 2010 Elsevier Masson SAS. All rights reserved.
• NOVEL OXIME DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Domain Therapeutics

  公开号：EP2493871B1

  公开（公告）日：2014-09-03
• POLYURETHANE, POLYURETHANE PRODUCTION METHOD, CONDUCTIVE PASTE COMPOSITION, CONDUCTIVE WIRE, AND METHOD FOR PRODUCING CONDUCTIVE WIRE
  申请人：SHIN-ETSU CHEMICAL CO., LTD.

  公开号：US20220157484A1

  公开（公告）日：2022-05-19

  A polyurethane contains a weakly acidic functional group having a pKa of 5 to 11. Thus, the present invention provides: a conductive paste composition for forming a stretchable conductive wire which varies slightly in electric conductivity at the time of elongation and shrinkage; and a polyurethane for providing the composition.
• US8962627B2
  申请人：——

  公开号：US8962627B2

  公开（公告）日：2015-02-24