N-acetyl-S-farnesyl-DL-cysteine | 141270-81-7

• 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: N-acetyl-S-farnesyl-DL-cysteine
• 英文别名: AFC；N-acetyl-S-farnesyl-L-cysteine；N-acetyl-S-farnesylcysteine；2-acetamido-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylpropanoic acid
• CAS: 141270-81-7
• 化学式: C₂₀H₃₃NO₃S
• 分子量: 367.553
• InChiKey: XTURYZYJYQRJDO-JTCWOHKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  D-苯甘氨醇 、 N-acetyl-S-farnesyl-DL-cysteine 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-acetyl-S-farnesyl-DL-cysteine-(D)-α-phenylglycinolamide
  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
• 作为产物：
  描述：

  trans,trans-farnesyl-DL-cysteine 、 乙酸酐 在 sodium hydroxide 作用下， 以43%的产率得到N-acetyl-S-farnesyl-DL-cysteine
  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

• Compounds and methods for use in treating neoplasia and cancer based upon inhibitors of isoprenylcysteine methyltransferase
  申请人：Gibbs A. Richard

  公开号：US20070004803A1

  公开（公告）日：2007-01-04

  The present invention relates to a novel method for the treatment of neoplasia, including cancer and other diseases and conditions in humans and mammals. More particularly, in preferred aspects, the present invention provides a method for the use of prenylcysteine analogs for the treatment of neoplasia, hyperproliferative cell growth including psoriasis, restenosis following cardiovascular surgery, hyperplasia, including renal hyperplasia, chronic inflammatory diseases including rheumatoid and osteoarthritis, among others.

  本发明涉及一种新的治疗肿瘤的方法，包括癌症和其他人类和哺乳动物疾病和病况的治疗。更具体地，在首选方面，本发明提供了一种使用戊二烯基半胱氨酸类似物治疗肿瘤、包括牛皮癣、心血管手术后再狭窄、包括肾脏增生的增生、包括类风湿和骨关节炎等慢性炎症疾病的方法。
• Acid Mimic Compounds for the Inhibition of Isoprenyl-S-Cysteinyl Methyltransferase
  申请人：Lee Seung-Yub

  公开号：US20090170917A1

  公开（公告）日：2009-07-02

  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).

  本发明提供了一种新型化合物，能够有效抑制由G蛋白或GPCR介导的中性粒细胞、巨噬细胞和血小板的炎症反应。特别地，本发明的化合物作为水肿抑制剂、红斑抑制剂和MPO（髓过氧化物酶）抑制剂，以及含有这些化合物的制药组合物，并用于治疗可能受益于水肿、红斑和MPO抑制的疾病，如炎症（急性或慢性）、哮喘、自身免疫性疾病和慢性阻塞性肺疾病（例如肺气肿、慢性支气管炎和小气道疾病等）、免疫系统的炎症反应、皮肤疾病（例如减少患有酒渣鼻、特应性皮炎、脂溢性皮炎、银屑病的患者的急性皮肤刺激）、肠易激综合征（例如克罗恩病和溃疡性结肠炎等）和中枢神经系统疾病（例如帕金森病）。
• USRE39682E1
  申请人：——

  公开号：USRE39682E1

  公开（公告）日：2007-06-05
• [EN] ACID MIMIC COMPOUNDS FOR THE INHIBITION OF ISOPRENYL-S-CYSTEINYL METHYLTRANSFERASE<br/>[FR] COMPOSÉS MIMIQUES D'ACIDE POUR L'INHIBITION D'ISOPRÉNYL-S-CYCTÉINYLMÉTHYLTRANSFÉRASE
  申请人：SIGNUM BIOSCIENCES INC

  公开号：WO2009073665A1

  公开（公告）日：2009-06-11

  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.