6,8-Dimethyl-2-pyridin-4-ylquinoline-4-carboxylic acid | 436092-56-7

• 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: 6,8-Dimethyl-2-pyridin-4-ylquinoline-4-carboxylic acid
• CAS: 436092-56-7
• 化学式: C₁₇H₁₄N₂O₂
• mdl: MFCD03421950
• 分子量: 278.31
• InChiKey: IFBPTCBOCMBOTI-UHFFFAOYSA-N

物化性质

• 沸点：
  489.8±45.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,8-Dimethyl-2-pyridin-4-ylquinoline-4-carboxylic acid 在 氯化亚砜 作用下， 反应 2.0h， 生成 6,8-Dimethyl-2-pyridin-4-ylquinoline-4-carbonyl chloride hydrochloride
  参考文献：
  名称：

  Cytochrome P450 2C9 Type II Binding Studies on Quinoline-4-Carboxamide Analogues

  摘要：

  CYP2C9 is a significant P450 protein responsible for drug metabolism. With the increased use of heterocyclic compounds in drug design, a rapid and efficient predrug screening of these potential type II binding compounds is essential to avoid adverse drug reactions. To understand binding modes, we use quinoline-4-carboxamide analogues to study the factors that determine the structure-activity relationships. The results of this study suggest that the more accessible pyridine with the nitrogen para to the linkage can coordinate directly with the ferric heme iron, but this is not seen for the meta or ortho isomers. The pi-cation interaction of the naphthalene moiety and Arg 108 residue may also assist in stabilizing Substrate binding within the active-site cavity. The type II substrate binding affinity is determined by the combination of steric, electrostatic, and hydrophobicity factors; meanwhile, it is enhanced by the strength of lone pair electrons coordination with the heme iron.

  DOI：

  10.1021/jm8011257
• 作为产物：
  描述：

  4-乙酰吡啶 、 5,7-二甲基靛红 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 6,8-Dimethyl-2-pyridin-4-ylquinoline-4-carboxylic acid
  参考文献：
  名称：

  Cytochrome P450 2C9 Type II Binding Studies on Quinoline-4-Carboxamide Analogues

  摘要：

  CYP2C9 is a significant P450 protein responsible for drug metabolism. With the increased use of heterocyclic compounds in drug design, a rapid and efficient predrug screening of these potential type II binding compounds is essential to avoid adverse drug reactions. To understand binding modes, we use quinoline-4-carboxamide analogues to study the factors that determine the structure-activity relationships. The results of this study suggest that the more accessible pyridine with the nitrogen para to the linkage can coordinate directly with the ferric heme iron, but this is not seen for the meta or ortho isomers. The pi-cation interaction of the naphthalene moiety and Arg 108 residue may also assist in stabilizing Substrate binding within the active-site cavity. The type II substrate binding affinity is determined by the combination of steric, electrostatic, and hydrophobicity factors; meanwhile, it is enhanced by the strength of lone pair electrons coordination with the heme iron.

  DOI：

  10.1021/jm8011257

文献信息

• AMINOTHIAZOLE DERIVATIVES AS HUMAN STEAROYL-COA DESATURASE INHIBITORS
  申请人：Fu Jianmin

  公开号：US20100152187A1

  公开（公告）日：2010-06-17

  Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I), where V, W, R 1 , R 2 , R 3 and R 4 are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明揭示了治疗哺乳动物，特别是人类SCD介导的疾病或病情的方法，其中方法包括向需要该方法的哺乳动物（例如人类）给予式(I)化合物，其中V、W、R1、R2、R3和R4的定义如本文所述。本发明还揭示了包含式(I)化合物的制药组合物。
• Arminothiazole derivatives as human stearoyl-coa desaturase inhibitors
  申请人：Xenon Pharmaceuticals Inc.

  公开号：EP2540296A1

  公开（公告）日：2013-01-02

  Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where V, W, R1, R2, R3 and R4 are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

  本发明公开了治疗哺乳动物（最好是人类）SCD 介导的疾病或病症的方法，其中这些方法包括向有需要的哺乳动物施用式 (I) 化合物： 其中 V、W、R1、R2、R3 和 R4 在本文中定义。还公开了包含式（I）化合物的药物组合物。
• US8541457B2
  申请人：——

  公开号：US8541457B2

  公开（公告）日：2013-09-24
• [EN] AMINOTHIAZOLE DERIVATIVES AS HUMAN STEAROYL-COA DESATURASE INHIBITORS<br/>[FR] DERIVES AMINOTHIAZOLE UTILISES EN TANT QU'INHIBITEURS DE LA STEAROYLE-COA DESATURASE HUMAINE
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2007130075A1

  公开（公告）日：2007-11-15

  [EN] Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I), where V, W, R¹, R², R³ and R⁴ are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.
  [FR] La présente invention concerne des procédés visant à traiter une maladie ou un trouble véhiculé par la stéaroyle-CoA désaturase (SCD) chez un mammifère, de préférence un être humain, ledit procédé impliquant d'administrer à un mammifère le nécessitant un composé de formule (I), dans laquelle V, W, R¹, R², R³ et R⁴ sont tels que définis dans la description. L'invention concerne également des compositions pharmaceutiques comprenant les composés de formule (I).
• Cytochrome P450 2C9 Type II Binding Studies on Quinoline-4-Carboxamide Analogues
  作者：Chi-Chi Peng、Jonathan L. Cape、Tom Rushmore、Gregory J. Crouch、Jeffrey P. Jones

  DOI：10.1021/jm8011257

  日期：2008.12.25

  CYP2C9 is a significant P450 protein responsible for drug metabolism. With the increased use of heterocyclic compounds in drug design, a rapid and efficient predrug screening of these potential type II binding compounds is essential to avoid adverse drug reactions. To understand binding modes, we use quinoline-4-carboxamide analogues to study the factors that determine the structure-activity relationships. The results of this study suggest that the more accessible pyridine with the nitrogen para to the linkage can coordinate directly with the ferric heme iron, but this is not seen for the meta or ortho isomers. The pi-cation interaction of the naphthalene moiety and Arg 108 residue may also assist in stabilizing Substrate binding within the active-site cavity. The type II substrate binding affinity is determined by the combination of steric, electrostatic, and hydrophobicity factors; meanwhile, it is enhanced by the strength of lone pair electrons coordination with the heme iron.