Hamilton FTI-276

• 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: Hamilton FTI-276
• 英文别名: FTI-276；FTI-276 trifluoroacetate salt；(2S)-2-[[4-[[(2R)-2-amino-3-sulfanylpropyl]amino]-2-phenylbenzoyl]amino]-4-methylsulfanylbutanoic acid;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₁H₂₇N₃O₃S₂
• 分子量: 547.62
• InChiKey: IAVHISGQCODLHL-WSCVZUBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  168
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N-[4-nitro-2-phenylbenzoyl]-methionine methyl ester 在 盐酸 、 三乙基硅烷 、 lithium hydroxide 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 18.17h， 生成 Hamilton FTI-276
  参考文献：
  名称：

  Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors

  摘要：

  Cysteine farnesylation at the carboxylate terminal tetrapeptide CAAX of Ras protein is catalyzed by farnesyltransferase. This lipid modification is necessary for regulatory function of both normal and oncogenic Ras. The high frequency of Ras mutation in human cancers has prompted an intensive study on finding ways of controlling oncogenic Ras function. Inhibition of farnesyltransferase is among the most sought after targets for cancer chemotherapy. We report here the design, synthesis and biological characterization of a series of peptidomimetics as farnesyltransferase inhibitors. These compounds are extremely potent towards farnesyltransferase with IC50 values ranging from subnanomolar to low nanomolar concentrations. They have a high selectivity for farnesyltransferase over the closely related geranylgeranyltransferase-I. Structure-activity relationship studies demonstrated that a properly positioned hydrophobic group significantly enhanced inhibition potency, reflecting an improved complementarity to the large hydrophobic pocket in the CAAX binding site. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00252-7

文献信息

• Therapeutic compositions comprising chorionic gonadotropins and HMG CoA reductase inhibitors
  申请人：Dent Paul

  公开号：US20080139457A1

  公开（公告）日：2008-06-12

  The invention provides improved methods and compositions for the treatment of cancer in a subject comprising administering to said subject a therapeutically effective amount of a composition comprising a chorionic gonadotropin or a therapeutically active fragment or analogue thereof in combination with an HMG CoA reductase inhibitor. The compositions and methods may also comprise geranylgeranyltransferase inhibitors (GGTI) and farnesyltransferase inhibitors (FTI) instead of or in addition to the HMG CoA reductase inhibitors of the invention.
• [EN] THERAPEUTIC COMPOSITIONS COMPRISING CHORIONIC GONADOTROPINS AND HMG COA REDUCTASE INHIBITORS<br/>[FR] COMPOSITIONS THERAPEUTIQUES COMPRENANT DES GONADOTROPINES CHORIONIQUES ET DES INHIBITEURS DE LA REDUCTASE HMG COA
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2007035395A9

  公开（公告）日：2007-06-14

  [EN] The invention provides improved methods and compositions for the treatment of cancer in a subject comprising administering to said subject a therapeutically effective amount of a composition comprising a chorionic gonadotropin or a therapeutically active fragment or analogue thereof in combination with an HMG CoA reductase inhibitor. The compositions and methods may also comprise geranylgeranyltransferase inhibitors (GGTI) and farnesyltransferase inhibitors (FTI) instead of or in addition to the HMG CoA reductase inhibitors of the invention.
  [FR] L'invention porte sur des méthodes et sur des compositions améliorées destinées à être utilisées dans le traitement du cancer et consistant à administrer à un sujet une quantité efficace d'un point de vue thérapeutique d'une composition comprenant une gonadotropine chorionique ou un fragment actif d'un point de vue thérapeutique de celle-ci ou un analogue de celle-ci en combinaison avec un inhibiteur de la réductase HMG CoA. Les compositions et les méthodes de cette invention peuvent également comprendre des inhibiteurs de géranylgéranyltransférase (GGTI) et des inhibiteurs de farnésyltransférase (FTI) en remplacement ou en plus des inhibiteurs de la réduction HMG CoA de l'invention.