Claims for Patent: 5,292,756

Summary for Patent: 5,292,756

Title:	Novel sulfonamide fibrinogen receptor antagonists
Abstract:	A series of non-peptide derivatives of the formula ##STR1## 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), Egbertson; Melissa S. (Ambler, PA), Halczenko; Wasyl (Hatfield, PA), Hartman; George D. (Lansdale, PA)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	07/860,747
Patent Claims:	1. A compound of the structural formula ##STR216## and the pharmaceutically acceptable salts 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 oxazale; R.sup.5 is ##STR217## wherein R.sup.8 is hydroxy or C.sub.1-10 alkyloxy, ##STR218## 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 ##STR219## p is zero or one; and m is an integer from two to six. 2. A compound of claim 1, ##STR220## and the pharmaceutically acceptable salts 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 ##STR221## wherein R.sup.8 is hydroxy or C.sub.1-10 alkyloxy, ##STR222## 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. 3. A compound as claimed in claim 2, of the structural formula ##STR223## 4. A compound as claimed in claim 2, of the structural formula ##STR224## 5. A compound as claimed in claim 2, of the structural formula ##STR225## 6. A compound of claim 1 selected from the group consisting of 2-S-(2-Styrylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propionic acid hydrochloride; 2-S-(Phenylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propionic acid hydrochloride; 2-S-(2-Phenethylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propioni c acid hydrochloride; 2-S-(2-Thienylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propionic acid hydrochloride; {2-[4-[4-Piperidin-4-yl)butyloxyphenyl]1-n-butylsulfonylamino)}ethanephosph onic acid ethyl ester; {2-[4-[4-Piperidin-4-yl)butyloxyphenyl]1n-butylsulfonylamino)}ethanephospho nic acid; and Ethyl-2-S-Benzylsulfonylamino-3-[4-(piperidin-4-yl)butyloxyphenyl]propionat e; 2-S-(Butylsulfonylamino)-3-[4-(piperidin-4-yl)-1,1-dimethyl-butyloxyphenyl] propionic acid; and 3-S-(Butylsulfonylamino)-4-[4-piperidin-4-yl)butyloxyphenyl]butanoic acid. 7. A pharmaceutical composition, comprising a compound as claimed in claim 2, and a pharmaceutically acceptable carrier. 8. A pharmaceutical composition, comprising the compound as claimed in claim 3, and a pharmaceutically acceptable carrier. 9. A pharmaceutical composition, comprising the compound as claimed in claim 4, and a pharmaceutically acceptable carrier. 10. A pharmaceutical composition, comprising the compound as claimed in claim 5, and a pharmaceutically acceptable carrier. 11. A pharmaceutical composition, comprising a compound as claimed in claim 6, and a pharmaceutically acceptable carrier. 12. A method of blocking fibrinogen from acting at its platelet receptor site in a mannal, comprising the step of administering to said mammal a pharmacologically effective amount of a compound as claimed in claim 2. 13. The method as claimed in claim 12, wherein said compound is ##STR226## 14. The method as claimed in claim 12, wherein said compound is ##STR227## 15. The method as claimed in claim 12, wherein said compound is ##STR228## 16. The method as claimed in claim 12, wherein said compound is selected from 2-S-(2-Styrylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propionic acid hydrochloride; 2-S-(Phenylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]-propionic acid hydrochloride; 2-S-(2-Phenethylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propioni c acid hydrochloride; 2-S-(2-Thienylsulfonylamino)-3-[4-(piperidin-4-yl)butyloxyphenyl]propionic acid hydrochloride; {2-[4-[4-Piperidin-4-yl)butyloxyphenyl]-1-n-butylsulfonylamino)}ethanephosp honic acid ethyl ester; {2-[4-[4-Piperidin-4-yl)butyloxyphenyl]-1-n-butylsulfonylamino)}ethanephosp honic acid; and Ethyl-2-S-Benzylsulfonylamino-3-[4-(piperidin-4-yl)butyloxyphenyl]propionat e; 2-S-(Butylsulfonylamino)-3-[4-(piperidin-4-yl)-1,1-dimethyl-butyloxphenyl]p ropionic acid; and 3-S-(Butylsulfonylamino)-4-[4-piperidin-4-yl)butyloxyphenyl]butanoic acid.