- Orally active thrombin inhibitors. Part 1: Optimization of the P1-moiety
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The synthesis and SAR of novel nanomolar thrombin inhibitors with the common backbone HOOC-CH2-d-cyclohexylalanyl-3,4-dehydroprolyl-NH-CH 2-aryl-C(double bond, long NH)NH2 are described together with their ecarin clotting
- Mack, Helmut,Baucke, Dorit,Hornberger, Wilfried,Lange, Udo E.W.,Seitz, Werner,Hoeffken, H. Wolfgang
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p. 2641 - 2647
(2008/12/21)
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- Technical scale synthesis of a new and highly potent thrombin inhibitor
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In this account, we describe the development of an efficient and convergent process for the peptidomimetic thrombin inhibitor 1 on production plant scale. Starting from nicotinonitrile (13), (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2- pyrrolidinecarboxylic acid (5) and (2R)-2-amino-3-cyclohexylpropanoic acid (29) compound 1 was obtained in 16 chemical steps. New methods had been developed for the preparation of the key intermediate dehydroproline 22 and the transformation of nitriles into amidines. The thrombin inhibitor 1 was isolated by special techniques (nanofiltration and spray drying). Almost all salts of 1 are amorphous, however, a crystalline complex was obtained with 1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Saccharin).
- Bernard, Harald,Buelow, Gerd,Lange, Udo E. W.,Mack, Helmut,Pfeiffer, Thomas,Schaefer, Bernd,Seitz, Werner,Zierke, Thomas
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p. 2367 - 2375
(2007/10/03)
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- Thrombin inhibitors
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Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents.
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Page column 28
(2010/02/06)
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