salirasib | 1092521-74-8

• 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: salirasib
• 英文别名: farnesylthiosalicylic acid amide；farnesylthiosalicylicylamide；S-trans,trans-farnesylthiosalicylamide；Farnesyl Thiosalicylic Acid Amide；2-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylbenzamide
• CAS: 1092521-74-8
• 化学式: C₂₂H₃₁NOS
• 分子量: 357.56
• InChiKey: GZTMFRUGZMZCRD-CFBAGHHKSA-N

物化性质

• 沸点：
  497.6±45.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、乙醇

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  法尼基硫代水杨酸 在 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以87%的产率得到salirasib
  参考文献：
  名称：

  New Derivatives of Farnesylthiosalicylic Acid (Salirasib) for Cancer Treatment: Farnesylthiosalicylamide Inhibits Tumor Growth in Nude Mice Models

  摘要：

  The Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS, Salirasib) interferes with Ras membrane interactions that are crucial for Ras-dependent transformation. It remains unknown whether modifications of the carboxyl group of FTS can affect its activity. Here we show that specific modifications of the FrS carboxyl group by esterification or amidation yield compounds with improved growth inhibitory activity, compared to FTS, as shown in Panc-1 and U87 cells. The most potent compounds were FTS-methoxymethyl ester and FTS-amide. However, selectivity toward active Ras-GTP, as known for FrS, was apparent with the amide derivatives of FTS. FTS-amide exhibited the overall highest efficacy in inhibition of Ras-GTP and cell growth. This new compound significantly inhibited growth of both Panc-1 tumors and U87 brain tumors. Thus amide derivatives of the FTS carboxyl group provide potent cell-growth inhibitors without loss of selectivity toward the active Ras protein and may serve as new candidates in cancer therapy.

  DOI：

  10.1021/jm801165r

文献信息

• FORMULATIONS AND CARRIER SYSTEMS INCLUDING FARNESYLTHIOSALYCYLIC MOITIES
  申请人：University of Pittsburgh - Of the Commonwealth System of Higher Education

  公开号：US20150231271A1

  公开（公告）日：2015-08-20

  A method of forming or creating a formulation for a compound to be delivered includes creating a carrier agent by conjugating at least one hydrophobic domain or hydrophobic compound with at least one hydrophilic domain or hydrophilic compound and associating the compound to be delivered with the carrier agent to create the formulation. The at least one hydrophobic compound has the formula: wherein R1 is a farnesyl group, a geranyl group or geranyl-geranyl group, X is O, S, SO, SO 2 , NH or Se, Z is C—R 2 or N, R 2 is H, CN, CO 2 R 7 , SO 3 R 7 , CONR 7 R 8 or SO 2 NR 7 R 8 , wherein R 7 and R 8 are each independently H, an alkyl group, an alkenyl group, CO 2 M or SO 3 M, wherein M is a cation and R 3 , R 4 , and R 5 are independently H, a carboxyl group, an alkyl group, an alkenyl group, an aminoalkyl group, a nitroalkyl group, a nitro group, a halo atom, an amino group, a mono-alkylamino group, a di-alkylamino group, mercapto group, a mercaptoalkyl group, an azido group or a thiocyanato group. A plurality of the carrier agents are adapted to assemble into a structure. The hydrophobic compound is cleavably conjugated to the at least one hydrophilic compound via a linkage which is labile in vivo.

  形成或创建化合物配方的方法包括通过将至少一个疏水域或疏水化合物与至少一个亲水域或亲水化合物结合来创建载体剂，并将待传递的化合物与载体剂结合以创建配方。至少一个疏水化合物具有以下结构式： 其中R1是一种法尼基基团、一种蒈基团或蒈基-蒈基团，X是O、S、SO、SO2、NH或Se，Z是C—R2或N，R2是H、CN、CO2R7、SO3R7、CONR7R8或SO2NR7R8，其中R7和R8各自独立地是H、烷基基团、烯基基团、CO2M或SO3M，其中M是阳离子，而R3、R4和R5独立地是H、羧基、烷基基团、烯基基团、氨基烷基基团、硝基烷基基团、硝基、卤原子、氨基、单烷基氨基基团、双烷基氨基基团、巯基、巯基烷基基团、叠氮基或硫氰基。多种载体剂适应组装成一种结构。疏水化合物通过在体内易裂解的连接物与至少一个亲水化合物可解离地结合。
• Formulations and carrier systems including farnesylthiosalicylic moieties
  申请人：University of Pittsburgh—Of the Commonwealth System of Higher Education

  公开号：US10376591B2

  公开（公告）日：2019-08-13

  A formulation includes a carrier agent formed by conjugating at least one biologically active hydrophobic compound with at least one hydrophilic compound, the at least one biologically active hydrophobic compound selected from the group of farnesylthiosalicylic acid and a derivative of farnesylthiosalicylic acid which is biologically active as an RAS antagonist, wherein a plurality of the carrier agents are adapted to assemble into a structure and the at least one biologically active hydrophobic compound is conjugated with the at least one hydrophilic compound via a linkage which is labile in vivo, and a biologically active compound associated with the carrier agent.

  一种制剂包括通过将至少一种具有生物活性的疏水化合物与至少一种亲水化合物共轭而形成的载体剂，该至少一种具有生物活性的疏水化合物选自法呢基硫代水杨酸和法呢基硫代水杨酸的衍生物，该衍生物具有作为 RAS 拮抗剂的生物活性、其中多个载体制剂可组合成一个结构，至少一种生物活性疏水化合物通过一种在体内易变的连接方式与至少一种亲水化合物共轭，以及一种与载体制剂相关的生物活性化合物。
• FORMULATIONS AND CARRIER SYSTEMS INCLUDING FARNESYLTHIOSALICYLIC MOIETIES
  申请人：University of Pittsburgh - Of the Commonwealth System of Higher Education

  公开号：US20180000957A1

  公开（公告）日：2018-01-04

  A formulation includes a carrier agent formed by conjugating at least one biologically active hydrophobic compound with at least one hydrophilic compound, the at least one biologically active hydrophobic compound selected from the group of farnesylthiosalicylic acid and a derivative of farnesylthiosalicylic acid which is biologically active as an RAS antagonist, wherein a plurality of the carrier agents are adapted to assemble into a structure and the at least one biologically active hydrophobic compound is conjugated with the at least one hydrophilic compound via a linkage which is labile in vivo, and a biologically active compound associated with the carrier agent.
• US9855341B2
  申请人：——

  公开号：US9855341B2

  公开（公告）日：2018-01-02
• New Derivatives of Farnesylthiosalicylic Acid (Salirasib) for Cancer Treatment: Farnesylthiosalicylamide Inhibits Tumor Growth in Nude Mice Models
  作者：Liat Goldberg、Roni Haklai、Victor Bauer、Aaron Heiss、Yoel Kloog

  DOI：10.1021/jm801165r

  日期：2009.1.8

  The Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS, Salirasib) interferes with Ras membrane interactions that are crucial for Ras-dependent transformation. It remains unknown whether modifications of the carboxyl group of FTS can affect its activity. Here we show that specific modifications of the FrS carboxyl group by esterification or amidation yield compounds with improved growth inhibitory activity, compared to FTS, as shown in Panc-1 and U87 cells. The most potent compounds were FTS-methoxymethyl ester and FTS-amide. However, selectivity toward active Ras-GTP, as known for FrS, was apparent with the amide derivatives of FTS. FTS-amide exhibited the overall highest efficacy in inhibition of Ras-GTP and cell growth. This new compound significantly inhibited growth of both Panc-1 tumors and U87 brain tumors. Thus amide derivatives of the FTS carboxyl group provide potent cell-growth inhibitors without loss of selectivity toward the active Ras protein and may serve as new candidates in cancer therapy.