5-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl}nicotinic acid | 1020658-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl}nicotinic acid
• 英文别名: 5-[2-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl]pyridine-3-carboxylic acid
• CAS: 1020658-32-5
• 化学式: C₂₁H₁₈BrFN₄O₃
• 分子量: 473.301
• InChiKey: XOUHTFHLCHSXCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  88.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(5-氯嘧啶-2-基)哌啶-4-醇 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 、 三环己基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 21.0h， 生成 5-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl}nicotinic acid
  参考文献：
  名称：

  Nicotinic acids: Liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy

  摘要：

  An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver-targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.040

文献信息

• AZACYCLOALKANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Oballa Renata M.

  公开号：US20100004245A1

  公开（公告）日：2010-01-07

  Azacycloalkane derivatives of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.

  结构式（I）的Azacycloalkane衍生物是选择性抑制stearoyl-coenzyme A delta-9去饱和酶（SCD1）相对于其他已知的stearoyl-coenzyme A去饱和酶的化合物。本发明的化合物对于预防和治疗与异常脂质合成和代谢有关的疾病非常有用，包括心血管疾病，如动脉粥样硬化；肥胖症；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗和肝脂肪变性。
• WO2008/46226
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] AZACYCLOALKANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] Dérivés d'azacycloalcane en tant qu'inhibiteurs de la stéaroyl-coenzyme A delta-9 désaturase
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2008046226A1

  公开（公告）日：2008-04-24

  [EN] Azacycloalkane derivatives of structural formula (I) are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.
  [FR] L'invention concerne des dérivés d'azacycloalcane de formule structurale (I), lesdits dérivés étant des inhibiteurs sélectifs de la stéaroyl-coenzyme A delta-9 désaturase (SCD1) par rapport à d'autres stéaroyl-coenzyme A désaturases connues. Les composés selon la présente invention sont utiles pour la prévention et le traitement de maladies associées à une synthèse et un métabolisme lipidiques anormaux, notamment les maladies cardiovasculaires, telles que l'athérosclérose ; l'obésité ; le diabète ; les maladies neurologiques ; le syndrome métabolique ; la résistance à l'insuline ; et la stéatose du foie.
• Nicotinic acids: Liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy
  作者：David A. Powell、W. Cameron Black、Kelly Bleasby、Chi-Chung Chan、Denis Deschenes、Marc Gagnon、Rob Gordon、Jocelyne Guay、Sebastien Guiral、Michael J. Hafey、Zheng Huang、Elise Isabel、Yves Leblanc、Angela Styhler、Li-Jing Xu、Lei Zhang、Renata M. Oballa

  DOI：10.1016/j.bmcl.2011.10.040

  日期：2011.12

  An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver-targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity. (C) 2011 Elsevier Ltd. All rights reserved.