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US 5,670,479 AGranted
.alpha.-ketoamide derivatives as inhibitors of thrombosis
AssigneeCorvas International, Inc.
InventorsMatthew M. Abelman, Daniel A. Pearson, George P. Vlasuk, Thomas R. Webb
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Abstract
a-Ketoamide derivatives, their pharmaceutically acceptable salts, compositions, diagnostic compositions and pharmaceutical compositions, which are useful for preventing or treating in a mammal a pathological condition characterized by thrombosis are described. a-Ketoamide derivatives, their pharmaceutically acceptable salts, compositions and diagnostic compositions, which are useful for in vivo imaging of thrombi in a mammal are also described. Methods of preventing or treating in a mammal a pathological condition characterized by thrombosis and methods of in vivo imaging of thrombi in a mammal are also disclosed.
Claims60
A compound having the formula:
- ##STR60## wherein R.sub.1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms;
- A is selected from the group consisting of ##STR61## wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to about 6 carbon atoms or alkyl of about 6 to about 15 carbon atoms;
- m is 1, 2 or 3;
- B is selected from the group consisting of -Gly-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-;
- C is selected from the group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH.sub.2, and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH.sub.2 ;
- or pharmaceutically acceptable salt thereof.
3 more elements
A compound having the formula:
- ##STR72## wherein R.sup.1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms;
- A is selected from the group consisting of ##STR73## wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms;
- m is 1, 2 or 3;
- D is selected from the group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-,
- wherein X has the formula:
- ##STR74## wherein R is an integer selected from R to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group;
- E is selected from the group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH.sub.R, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH.sub.2, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH.sub.2, and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH.sub.2 ;
- or pharmaceutically acceptable salt thereof.
5 more elements
Dependencies are inferred from the claim text.