{5-[1-[(Dodecyl-methyl-carbamoyl)-methyl]-2-(4-fluoro-benzylsulfanyl)-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl]-2-oxo-2H-pyrimidin-1-yl}-acetic acid ethyl ester | 259532-13-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: {5-[1-[(Dodecyl-methyl-carbamoyl)-methyl]-2-(4-fluoro-benzylsulfanyl)-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl]-2-oxo-2H-pyrimidin-1-yl}-acetic acid ethyl ester
• 英文别名: 1-(N-(1-dodecyl)-N-methylaminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5-(1-ethoxycarbonylmethyl-2-oxopyrimid-5-ylmethyl)pyrimidin-4-one；ethyl 2-[5-[[1-[2-[dodecyl(methyl)amino]-2-oxoethyl]-2-[(4-fluorophenyl)methylsulfanyl]-4-oxopyrimidin-5-yl]methyl]-2-oxopyrimidin-1-yl]acetate
• CAS: 259532-13-3
• 化学式: C₃₅H₄₈FN₅O₅S
• 分子量: 669.861
• InChiKey: RBRHUWXJXFCGBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  47
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  137
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  {5-[1-[(Dodecyl-methyl-carbamoyl)-methyl]-2-(4-fluoro-benzylsulfanyl)-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl]-2-oxo-2H-pyrimidin-1-yl}-acetic acid ethyl ester 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 {5-[1-[(Dodecyl-methyl-carbamoyl)-methyl]-2-(4-fluoro-benzylsulfanyl)-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl]-2-oxo-2H-pyrimidin-1-yl}-acetic acid
  参考文献：
  名称：

  The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2

  摘要：

  Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A(2), has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble, CNS penetrant inhibitor suitable for intravenous administration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00038-5
• 作为产物：
  描述：

  2-(ethoxymethylene)-3-(2-methoxypyrimidin-5-yl)propionic acid ethyl ester 在 sodium hydroxide 、 草酰氯 、 B-溴代邻苯二氧硼烷 、 potassium carbonate 、 N-乙基异丙基胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 {5-[1-[(Dodecyl-methyl-carbamoyl)-methyl]-2-(4-fluoro-benzylsulfanyl)-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl]-2-oxo-2H-pyrimidin-1-yl}-acetic acid ethyl ester
  参考文献：
  名称：

  The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2

  摘要：

  Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A(2), has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble, CNS penetrant inhibitor suitable for intravenous administration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00038-5

文献信息

• Pyrimidinone derivatives for the treatment of atherosclerosis
  申请人：SmithKline Beecham p.l.c.

  公开号：US06559155B1

  公开（公告）日：2003-05-06

  Pyrimidones of formula (I) are inhibitors of the enzyme LpPLA2 and thereof use in treating inter alia atherosclerosis, in which: R1 is COOH or a salt thereof, COOR10, CONR11R12, CN or CH2OH; R2 is a mono- or bicyclic aromatic ring system or a mono- or bicyclic heteroaromatic ring system; R3 is C1-20alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-5alkyl, C1-10alkoxyC1-10alkyl, or an aromatic or heteroaromatic ring system; W is SO2 or a bond; X is O or S; and Y is a group of the formula A1—A2—A3 in which A1 and A3 each represent a bond or a straight chain or branched alkylene group, said alkylene group(s) containing a total of 1 to 10 carbon atoms and A2 represents a bond or O, S, SO, SO2, CO, C═CH2, CONH, NHCO, CR15R16, CH═CH or C═C, providing that when A2 is O, S, SO, SO2 or CONH, A3 contains at least two carbon atoms linking the A2 group and the CH2 group in formula (I).

  式(I)的嘧啶酮是LpPLA2酶的抑制剂，可用于治疗动脉粥样硬化等疾病，其中：R1是COOH或其盐，COOR10，CONR11R12，CN或CH2OH; R2是单环或双环芳香环系或单环或双环杂芳香环系; R3是C1-20烷基，C3-6环烷基，C3-6环烷基C1-5烷基，C1-10烷氧基C1-10烷基，或芳香环或杂芳香环系; W是SO2或键; X是O或S; Y是式A1-A2-A3的基团，其中A1和A3分别表示键或直链或支链烷基，所述烷基含有1至10个碳原子，并且A2表示键或O、S、SO、SO2、CO、C═CH2、CONH、NHCO、CR15R16、CH═CH或C═C，但当A2是O、S、SO、SO2或CONH时，A3含有至少两个碳原子连接式(I)中的A2基团和CH2基团。
• PYRIMIDINONE DERIVATIVES FOR THE TREATMENT OF ATHEROSCLEROSIS
  申请人：SmithKline Beecham plc

  公开号：EP1105377B1

  公开（公告）日：2003-10-08
• US6559155B1
  申请人：——

  公开号：US6559155B1

  公开（公告）日：2003-05-06
• [EN] PYRIMIDINONE DERIVATIVES FOR THE TREATMENT OF ATHEROSCLEROSIS<br/>[FR] DERIVES DE PYRIMIDINONE DESTINES AU TRAITEMENT DE L'ATHEROSCLEROSE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2000010980A1

  公开（公告）日：2000-03-02

  Pyrimidones of formula (I) are inhibitors of the enzyme LpPLA2 and thereof use in treating inter alia atherosclerosis. In formula (I), R1 is COOH or a salt thereof, COOR?10, CONR11R12¿, CN or CH¿2OH; R?2 is a mono- or bicyclic aromatic ring system or a mono- or bicyclic heteroaromatic ring system; R3 is C¿1-20?alkyl, C3-6cycloalkylC3-6cycloalkylC1-5alkyl, C1-10alkoxyC1-10alkyl, or an aromatic or heteroaromatic ring system; W is SO2 or a bond; X is O or S; and Y is a group of the formula A?1-A2-A3¿- in which A?1 and A3¿ each represent a bond or a straight chain or branched alkylene group, said alkylene group(s) containing a total of 1 to 10 carbon atoms and A2 represents a bond or O, S, SO, SO¿2?, CO, C=CH2, CONH, NHCO, CR?15R16¿, CH=CH or C C, providing that when A2 is O, S, SO, SO¿2? or CONH, A?3¿ contains at least two carbon atoms linking the A2 group and the CH¿2? group in formula (I).
• The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2
  作者：Helen F. Boyd、Beverley Hammond、Deirdre M.B. Hickey、Robert J. Ife、Colin A. Leach、V.Ann Lewis、Colin H. Macphee、Kevin J. Milliner、Ivan L. Pinto、Stephen A. Smith、Ian G. Stansfield、Colin J. Theobald、Caroline M. Whittaker

  DOI：10.1016/s0960-894x(01)00038-5

  日期：2001.3

  Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A(2), has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble, CNS penetrant inhibitor suitable for intravenous administration. (C) 2001 Elsevier Science Ltd. All rights reserved.