Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1991-02-08
1993-08-31
Lee, Lester L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 12, 514 14, 514 15, 514 16, 514 17, 514 18, 530324, 530325, 530326, 530327, 530328, 530329, 530330, 623 1, 623 11, A61K 3702, C07K 700, C07K 708, C07K 710
Patent
active
052409139
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, monosubstituted, 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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Bourdon Paul R.
Jablonski Jo-Ann M.
Maraganore John M.
Biogen Inc.
Lee Lester L.
Marks Andrew S.
Miraglia Loretta A.
Perkins Susan M.
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