S-(farnesyl-3-thio)pyruvic acid | 141198-57-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: S-(farnesyl-3-thio)pyruvic acid
• 英文别名: 2-oxo-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylpropanoic acid
• CAS: 141198-57-4
• 化学式: C₁₈H₂₈O₃S
• 分子量: 324.485
• InChiKey: OCFCWQWBHGOMFR-XGGJEREUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  22
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  反式,反式-金合欢醇 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 potassium trimethylsilonate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 20.67h， 生成 S-(farnesyl-3-thio)pyruvic acid
  参考文献：
  名称：

  Structure-activity studies on the retinal rod outer segment isoprenylated protein methyltransferase

  摘要：

  Structure-activity studies were performed on the retinal rod outer segment isoprenylated protein methyltransferase that transfers a methyl group from S-adenosylmethionine (AdoMet) to the carboxyl group of isoprenylated (farnesylated or geranylgeranylated) cysteine residues. This methyltransferase enzyme has been shown to methylate N-acetyl-S-farnesyl-L-cysteine (L-AFC, 1) and S-(farnesyl-3-thio)propionic acid (FTP, 2). It is shown here that the enzyme does not enzymatically process D-AFC (8), although D-AFC (8) is a mixed-type inhibitor of the enzyme. Small modifications in the FTP (2) structural series generally lead to inactive substrates. For example, neither the cis- nor the trans-acrylate derivatives of FTP (2) are substrates of the enzyme, but both are inhibitors of it. Alkyl substitutions at the 3-position of FTP (2), moreover, lead to inhibitors of the methyltransferase. Substituents at the 2-position of FTP (2), as in 2-methyl-S-(farnesyl-3-thio)propionic acid (MFTP, 28) or S-farnesyl-2-(thiomethyl)acrylic acid (FTMA, 31), produce active substrates. Modifications at the carboxyl moiety produce neither substrates nor inhibitors of the enzyme. The conclusion from this and earlier studies is that the methyltransferase is selective for an isoprenylated thiopropionate moiety. Small deviations from this minimally essential structure lead to the abolition of substrate activity.

  DOI：

  10.1021/ja00036a052

文献信息

• ACETYL MIMIC COMPOUNDS FOR THE INHIBITION OF ISOPRENYL-S-CYSTEINYL METHYLTRANSFERASE
  申请人：Signum Biosciences, Inc.

  公开号：EP2252277A2

  公开（公告）日：2010-11-24
• [EN] ACETYL MIMIC COMPOUNDS FOR THE INHIBITION OF ISOPRENYL-S-CYSTEINYL METHYLTRANSFERASE<br/>[FR] COMPOSÉS ACÉTYL-MIMÉTIQUES POUR INHIBER L'ISOPRÉNYL-S-CYSTÉINYLE MÉTHYLTRANFÉRASE
  申请人：SIGNUM BIOSCIENCES INC

  公开号：WO2009102997A2

  公开（公告）日：2009-08-20

  Among other things, the present invention provides novel compounds capable of effectively inhibiting inflammatory responses that are mediated by G-proteins or GPCRs in neutrophils, macrophages and platelets. In particular, compounds of the present invention act as inhibitors of edema, inhibitors of erythema and inhibitors of MPO (myeloperoxidase), pharmaceutical compositions containing the same compounds and the use thereof for the treatment of diseases that may benefit from edema, erythema and MPO inhibition, such as inflammation (acute or chronic), asthma, autoimmune diseases, and chronic obstructive pulmonary disease (COPD) (e.g., emphysema, chronic bronchitis and small airways disease, etc.), inflammatory responses of the immune system, skin diseases (e.g., reducing acute skin irritation for patients suffering from rosacea, atopic dermatitis, seborrheic dermatitis, psoriasis), irritable bowel syndrome (e.g., Chron's disease and ulcerative colitis, etc.), and central nervous system disorders (e.g., Parkinson's disease).
• Structure-activity studies on the retinal rod outer segment isoprenylated protein methyltransferase
  作者：Bryant A. Gilbert、Eng Wui Tan、Dolores Perez-Sala、Robert R. Rando

  DOI：10.1021/ja00036a052

  日期：1992.5

  Structure-activity studies were performed on the retinal rod outer segment isoprenylated protein methyltransferase that transfers a methyl group from S-adenosylmethionine (AdoMet) to the carboxyl group of isoprenylated (farnesylated or geranylgeranylated) cysteine residues. This methyltransferase enzyme has been shown to methylate N-acetyl-S-farnesyl-L-cysteine (L-AFC, 1) and S-(farnesyl-3-thio)propionic acid (FTP, 2). It is shown here that the enzyme does not enzymatically process D-AFC (8), although D-AFC (8) is a mixed-type inhibitor of the enzyme. Small modifications in the FTP (2) structural series generally lead to inactive substrates. For example, neither the cis- nor the trans-acrylate derivatives of FTP (2) are substrates of the enzyme, but both are inhibitors of it. Alkyl substitutions at the 3-position of FTP (2), moreover, lead to inhibitors of the methyltransferase. Substituents at the 2-position of FTP (2), as in 2-methyl-S-(farnesyl-3-thio)propionic acid (MFTP, 28) or S-farnesyl-2-(thiomethyl)acrylic acid (FTMA, 31), produce active substrates. Modifications at the carboxyl moiety produce neither substrates nor inhibitors of the enzyme. The conclusion from this and earlier studies is that the methyltransferase is selective for an isoprenylated thiopropionate moiety. Small deviations from this minimally essential structure lead to the abolition of substrate activity.