189339-73-9Relevant academic research and scientific papers
Structure-activity and crystallographic analysis of a new class of non- amide-based thrombin inhibitor
Lu, Tianbao,Soll, Richard M.,Illig, Carl R.,Bone, Roger,Murphy, Larry,Spurlino, John,Salemme, F. Raymond,Tomczuk, Bruce E.
, p. 79 - 82 (2007/10/03)
The structure-activity relationships of a novel series of non-amide- based thrombin inhibitors are described. Exploration of the P2 and the aryl binding region for this series has identified optimal groups for achieving nanomolar potency. The binding modes of these optimal groups have been confirmed by X-ray structural analysis.
Non-peptidic phenyl-based thrombin inhibitors: Exploring structural requirements of the S1 specificity pocket with amidines
Lu, Tianbao,Tomczuk, Bruce,Bone, Roger,Murphy, Larry,Salemme, F. Raymond,Soll, Richard M.
, p. 83 - 85 (2007/10/03)
We expand the structural requirements and structure-activity relationship of a novel class of non-peptidic aryl-based thrombin inhibitors through exploration of the S1 specificity pocket of thrombin using flexible and constrained amidines. The most active compound of this class is 11 with K(i) = 69 nM, which is ca. 15-fold less potent than constrained guanidine 5.
Amidino protease inhibitors
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, (2008/06/13)
Amidino and benzamidino compounds, including compounds of the formula: wherein R1-R4, R6-R9, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit a number of proteolytic enzymes are described. Also described are methods for preparing the compounds of Formula I.
In vitro evaluation and crystallographic analysis of a new class of selective, non-amide-based thrombin inhibitors
Lu, Tianbao,Tomczuk, Bruce,Illig, Carl R.,Bone, Roger,Murphy, Larry,Spurlino, John,Salemme, F. Raymond,Soll, Richard M.
, p. 1595 - 1600 (2007/10/03)
We describe the in vitro evaluation and crystallographic analysis of a new class of potent and selective, non-aminoacid-based, small-molecule thrombin inhibitors, exemplified by 14. This class of achiral inhibitors lacks an amide-based backbone, exhibits nM inhibition of thrombin, and is selective for thrombin. Compound 14 does not interact with the active-site catalytic apparatus and is anchored to the enzyme via a single network of hydrogen bonds to Asp 189 of the S1 pocket.
