Inhibitors of thrombin

Details Inhibitors of thrombin Inhibitors of thrombin

1992-07-31

1995-06-20

Warden, Jill

Drug, bio-affecting and body treating compositions

Radionuclide or intended radionuclide containing; adjuvant...

In an organic compound

530330, 514 18, C07K 510, A61K 3807

Patent

active

054259363

ABSTRACT:
This invention relates to novel biologically active molecules which bind to and inhibit thrombin. These molecules comprise a catalytic site directed moiety (CSDM) of the formula: ##STR1## wherein X is hydrogen or is characterized by a backbone chain consisting of from 1 to 100 atoms; R.sub.1 is selected from the group consisting of unsubstituted, mono-substituted, di-substituted and tri-substituted saturated ring structures; R.sub.2 is a bond or is characterized by a backbone chain consisting of from 1 to 5 atoms; R.sub.3 is a bond or is characterized by a backbone chain consisting of from 1 to 3 atoms; R.sub.4 is any amino acid; R.sub.5 is any L-amino acid which comprises a guanidinium- or amino-containing side chain group; R.sub.6 is a non-amide bond; and Y is characterized by a backbone chain consisting of from 1 to 9 atoms; or the formula: ##STR2## wherein R'.sub.1 is selected from the group consisting of unsubstituted, mono-substituted, di-substituted and tri-substituted ring structures; R'.sub.4 is any amino acid comprising a side chain group characterized by the capacity to accept a hydrogen bond at a pH of between about 5.5 and 9.5; and X, R.sub.2, R.sub.3, R.sub.5, R.sub.6 and Y are defined as above. Preferred thrombin inhibitors are further characterized by a anion binding exosite associating domain (ABEAM) and a linker portion of between 18.ANG. and 42.ANG. in length which connects the Y to the ABEAM. This invention also relates to compositions, combinations and methods which employ these molecules for therapeutic, prophylactic and diagnostic purposes.

REFERENCES:
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