(5-{2-(4-Fluoro-benzylsulfanyl)-1-[(methyl-octyl-carbamoyl)-methyl]-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl}-2-oxo-2H-pyrimidin-1-yl)-acetic acid | 259532-12-2

• 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-{2-(4-Fluoro-benzylsulfanyl)-1-[(methyl-octyl-carbamoyl)-methyl]-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl}-2-oxo-2H-pyrimidin-1-yl)-acetic acid
• 英文别名: 2-[5-[[2-[(4-Fluorophenyl)methylsulfanyl]-1-[2-[methyl(octyl)amino]-2-oxoethyl]-4-oxopyrimidin-5-yl]methyl]-2-oxopyrimidin-1-yl]acetic acid
• CAS: 259532-12-2
• 化学式: C₂₉H₃₆FN₅O₅S
• 分子量: 585.7
• InChiKey: FRDCMLAYXLLSQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  41
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-哌嗪酮 、 (5-{2-(4-Fluoro-benzylsulfanyl)-1-[(methyl-octyl-carbamoyl)-methyl]-4-oxo-1,4-dihydro-pyrimidin-5-ylmethyl}-2-oxo-2H-pyrimidin-1-yl)-acetic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-(2-(4-Fluoro-benzylsulfanyl)-4-oxo-5-{2-oxo-1-[2-oxo-2-(3-oxo-piperazin-1-yl)-ethyl]-1,2-dihydro-pyrimidin-5-ylmethyl}-4H-pyrimidin-1-yl)-N-methyl-N-octyl-acetamide
  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：

  ethyl 3-(2-methoxypyrimidin-5-yl)propionate 在 sodium hydroxide 、 草酰氯 、 B-溴代邻苯二氧硼烷 、 sodium hydride 、 potassium carbonate 、 N-乙基异丙基胺 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 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-{2-(4-Fluoro-benzylsulfanyl)-1-[(methyl-octyl-carbamoyl)-methyl]-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

文献信息

• 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.