|Title:||Sulfonamide fibrinogen receptor antagonists|
|Abstract:||A series of non-peptide derivatives that are antagonists of the fibrinogen IIb/IIIa receptor and thus are platelet anti-aggregation compounds useful in the prevention and treatment of diseases caused by thrombus formation.|
|Inventor(s):||Duggan; Mark E. (Narberth, PA), Halczenko; Wasyl (Hatfield, PA), Egbertson; Melissa S. (Ambler, PA), Hartman; George D. (Lansdale, PA), Laswell; William L. (Perkasie, PA)|
|Assignee:||Merck & Co., Inc. (Rahway, NJ)|
|Filing Date:||Dec 28, 1998|
|Claims:||1. A method for treating thrombus formation in a mammal in need thereof, comprising administering an effective amount of a compound of the structural formula ##STR209## or a pharmaceutically acceptable salt thereof, wherein R.sup.4 is aryl, C.sub.1-10 alkyl, or C.sub.4-10 aralkyl, wherein aryl is phenyl, pyridyl, thienyl, tetrazole or oxazole; ##STR210## wherein R.sup.8 is hydroxy or C.sub.1-10 alkyloxy, ##STR211## wherein R.sup.9 and R.sup.10 are selected from the group consisting of hydrogen, C.sub.1-10 alkyl and phenyl C.sub.1-4 alkyl; |
Z is ##STR212## p is zero or one; and m is an integer from two to six, in combination with an effective amount of fibrinolytic agent.
2. A method of claim 1, wherein the compound has the structural formula ##STR213## or a pharmaceutically acceptable salt thereof, wherein R.sup.4 is aryl, C.sub.1-10 alkyl, or C.sub.4-10 aralkyl, wherein aryl is phenyl, pyridyl, thiophenyl, tetrazole, or oxazole;
R.sup.5 is ##STR214## wherein R.sup.8 is hydroxy or C.sub.1-10 alkyloxy, ##STR215## wherein R.sup.9 and R.sup.10 are selected from the group consisting of hydrogen, C.sub.1-10 alkyl and phenyl C.sub.1-4 alkyl;
Z is O;
p is zero or one; and m is an integer from two to six and the fibrinolytic agent is selected from the group consisting of streptokinase and tissue plasminogen activator.
3. A method of claim 2, wherein the compound is ##STR216## or a pharmaceutically acceptable salt thereof, and the fibrinolytic agent is tissue plasminogen activator.
4. The method of claim 3, wherein the salt is ##STR217##
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