- 专利标题: Inhibitors of farnesyl-protein transferase
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申请号: US315171申请日: 1994-09-29
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公开(公告)号: US5585359A公开(公告)日: 1996-12-17
- 发明人: Michael J. Breslin , S. J. deSolms , Samuel L. Graham , John H. Hutchinson , Gerald E. Stokker
- 申请人: Michael J. Breslin , S. J. deSolms , Samuel L. Graham , John H. Hutchinson , Gerald E. Stokker
- 申请人地址: NJ Rahway
- 专利权人: Merck & Co., Inc.
- 当前专利权人: Merck & Co., Inc.
- 当前专利权人地址: NJ Rahway
- 主分类号: A61K38/55
- IPC分类号: A61K38/55 ; A61K38/00 ; A61P35/00 ; A61P43/00 ; C07C229/12 ; C07C229/22 ; C07C229/24 ; C07C229/26 ; C07C229/36 ; C07C237/12 ; C07C255/24 ; C07C323/60 ; C07K5/06 ; C07K5/08 ; C07K5/083 ; C07K5/00 ; C07K7/00 ; C07K17/00
摘要:
The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras farnesyl transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
公开/授权文献
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