1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridine-3-carboxylic acid | 185540-07-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridine-3-carboxylic acid
• 英文别名: 1-butyl-3-carboxy-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridine；1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 185540-07-2
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: VXKQLDCDOZVVJT-UHFFFAOYSA-N

物化性质

• 沸点：
  489.6±45.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridine-3-carboxylic acid 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridin-3-yl]-N'-(2,6-diisopropylphenyl)urea
  参考文献：
  名称：

  Synthesis and structure–activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O -acyltransferase (ACAT)

  摘要：

  The synthesis and structure-activity relationships of N-phenyl-N'-[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1-N-(n)butyl substitution, SM-32504 (3m), gave a potent ACAT inhibitor, in vitro, respectively. The most potent compound, SM-32504 (3m), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.045
• 作为产物：
  描述：

  N-{3-[hydroxy(3-methoxyphenyl)methyl]pyridin-2-yl}pivalamide 在 吡啶 、 盐酸 、 manganese(IV) oxide 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O -acyltransferase (ACAT)

  摘要：

  The synthesis and structure-activity relationships of N-phenyl-N'-[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1-N-(n)butyl substitution, SM-32504 (3m), gave a potent ACAT inhibitor, in vitro, respectively. The most potent compound, SM-32504 (3m), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.045

文献信息

• Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: Potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility
  作者：Hitoshi Ban、Masami Muraoka、Katsuhisa Ioriya、Naohito Ohashi

  DOI：10.1016/j.bmcl.2005.09.056

  日期：2006.1

  groups were synthesized in order to improve aqueous solubility and pharmacokinetic property. SMP-797 possessing (4-aminophenyl)ureido and 3-(hydroxypropoxyphenyl) moieties showed potent ACAT inhibitory activity and excellent oral efficacy.

  为了改善水溶性和药代动力学性质，合成了具有亲水性基团的4-芳基-1,8-萘啶-2（1H）-3-基脲衍生物。具有（4-氨基苯基）脲基和3-（羟基丙氧基苯基）部分的SMP-797显示出有效的ACAT抑制活性和优异的口服功效。
• Pyridone derivatives and process for preparing the same
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：US20010051732A1

  公开（公告）日：2001-12-13

  A process for preparing a pyridone derivative ( 4 ), which comprises reacting the compound ( 1 ) with a hypochlorite or a hypobromite or with lead tetraacetate to give the compound ( 2 ), and reacting the compound ( 2 ) with the compound ( 3 ). Said process is preferably especially from the standpoint of safety. 1 wherein R 1 is hydrogen, alkyl, substituted alkyl, etc.; Y 1 is hydrogen, alky, substituted alky, etc.; Y 2 and Y 3 are indenpently hydrogen, halogen, etc.; and L is alkyl, substituted alkyl, etc.

  一种制备吡啶酮衍生物（4）的方法，包括将化合物（1）与次氯酸盐或次溴酸盐或四乙酸铅反应以得到化合物（2），并将化合物（2）与化合物（3）反应。从安全角度考虑，该方法是首选的。其中R1为氢、烷基、取代烷基等；Y1为氢、烷基、取代烷基等；Y2和Y3独立地为氢、卤素等；L为烷基、取代烷基等。
• Naphthyridine derivatives
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：US06420381B1

  公开（公告）日：2002-07-16

  A compound of the formula (I): wherein Ring A is substituted or unsubstituted pyridine ring, Y is substituted or unsubstituted alkyl, etc., R1 is hydrogen, or substituted or unsubstituted alkyl, etc., R2 is hydrogen or lower alkyl, R3 is lower alkyl, Z is 1) —D1—Q [D1 is direct bond or divalent C1-8 hydrocarbon, etc., Q is hydroxy, carboxyl, etc.], or 2) —D2M—E—W [D2 is direct bond or divalent C1-8 hydrocarbon, etc., M is oxygen, sulfur, etc., E is direct bond or divalent C1-8 hydrocarbon, etc., W is hydroxyl, carboxyl, etc.], or a prodrug thereof, or a pharmaceutically acceptable salt of the same, which exhibits acyl-CoA: cholesterol acyl transferase (ACAT) inhibitory activity, and is useful as an agent for treatment of hyperlipidemia and atherosclerosis.

  化合物的化学式(I)：其中环A被取代或未取代的吡啶环所取代，Y是取代或未取代的烷基等，R1是氢，或取代或未取代的烷基等，R2是氢或较低的烷基，R3是较低的烷基，Z为1) —D1—Q [D1为直接键或双价的C1-8碳氢化合物等，Q为羟基，羧基等]，或2) —D2M—E—W [D2为直接键或双价的C1-8碳氢化合物等，M为氧，硫等，E为直接键或双价的C1-8碳氢化合物等，W为羟基，羧基等]，或其前药，或其药物学上可接受的盐，该化合物表现出酰基辅酶A:胆固醇酰基转移酶（ACAT）抑制活性，可用作治疗高脂血症和动脉粥样硬化的药物。
• NOVEL NAPHTHYRIDINE DERIVATIVES
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP0842933A1

  公开（公告）日：1998-05-20

  Naphthyridine derivative of the formula: wherein Ring A is substituted or unsubstituted pyridine, X is ―N(R2)―CO― (R2 is H, alkyl, substituted alkyl, etc.), Z is a direct bond, ―NH―, C1-C2 alkylene, or ―CH=CH―, Y is alkyl, substituted alkyl, aromatic group or substituted aromatic group, etc., B is alkyl, substituted alkyl, aromatic group or substituted aromatic group, or an acid addition salt thereof, these compounds having acyl-CoA: cholesterol acyl transferase inhibitory activity, and being useful as an agent for prophylaxis or treatment of hyperlipidemia, atherosclerosis, and related diseases thereof.

  式中的萘啶衍生物： 其中环 A 是取代或未取代的吡啶，X 是-N(R2)-CO-（R2 是 H、烷基、取代的烷基等），Z 是直接键、-NH-、C1-C2 亚烷基或-CH=CH-，Y 是烷基、取代的烷基、芳香基团或取代的芳香基团等、B 是烷基、取代的烷基、芳香基团或取代的芳香基团，或其酸加成盐，这些化合物具有酰基-CoA：胆固醇酰基转移酶抑制活性，可用作预防或治疗高脂血症、动脉粥样硬化及其相关疾病的药物。
• PYRIDONE DERIVATIVES AND PROCESS FOR PRODUCING THE SAME
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1086948A1

  公开（公告）日：2001-03-28

  A process for producing a pyridone derivative represented by general formula (4), characterized by reacting a compound represented by general formula (1) with a hypochlorite or hypobromite or with lead tetraacetate to give a compound represented by general formula (2) and reacting this compound with a compound represented by general formula (3). The process is preferable especially from the standpoint of safety. In said formulae, R1 represents hydrogen, alkyl, substituted alkyl, etc.; Y1 represents hydrogen, alkyl, substituted alkyl, etc.; Y2 and Y3 each independently represents hydrogen, halogeno, etc.; and L represents alkyl, substituted alkyl, etc.

  一种生产通式(4)所代表的吡啶酮衍生物的工艺，其特征是将通式(1)所代表的化合物与次氯酸盐或次溴酸盐或四乙酸铅反应，得到通式(2)所代表的化合物，再将该化合物与通式(3)所代表的化合物反应。从安全角度考虑，该工艺更可取。在上述通式中，R1 代表氢、烷基、取代烷基等；Y1 代表氢、烷基、取代烷基等；Y2 和 Y3 各自独立地代表氢、卤素等；L 代表烷基、取代烷基等。