Claims for Patent: 4,424,354

Summary for Patent: 4,424,354

Title:	Inhibitors of mammalian collagenase
Abstract:	Mammalian collagenase is inhibited by compounds of the formula ##STR1## or salts thereof, wherein R is hydrogen, alkanoyl of 2 to 10 carbon atoms or arylcarbonyl; R.sub.1 is of 3 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, aryl or arylalkyl; R.sub.2 is hydrogen, ##STR2## R.sub.3 is ##STR3## R.sub.4 is hydrogen, methyl, ethyl, or ##STR4## R.sub.5 and R.sub.6 are each independently selected as --OCH.sub.3 or --OCH.sub.2 CH.sub.3 or are combined as --OCH.sub.2 CH.sub.2 O-- or --O--(CH.sub.2).sub.3 --O--; R.sub.7 and R.sub.8 are each independently selected as hydrogen, methyl or ethyl or are combined as --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 -- or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 --; R.sub.9 is hydrogen, methyl, ethyl ##STR5## m is an integer from 0 to 7; p is an integer from 1 to 3; AA.sub.n is an amino acid chain of from one to three amino acids; n is 1 or 1, 2 or 1, 2, 3; when p is 1, AA.sub.n is AA.sub.1 ; when p is 2, AA.sub.n is AA.sub.1 -AA.sub.2 ; when p is 3, AA.sub.n is AA.sub.1 -AA.sub.2 -AA.sub.3 ; AA.sub.1 is glycine or alanine; AA.sub.2 is glycine or alanine; AA.sub.3 is leucine, glutamine or isoleucine. A method of reducing the adverse effects of mammalian collagenase in a mammalian host in need thereof, which comprises administering to the mammal an effective amount of a compound having the above formula is within the scope of the invention.
Inventor(s):	Sundeen; Joseph E. (Yardley, PA), Dejneka; Tamara (Skillman, NJ)
Assignee:	E. R. Squibb & Sons, Inc. (Princeton, NJ)
Application Number:	06/424,735
Patent Claims:	1. A compound of the formula ##STR196## or salts thereof wherein R is hydrogen, alkanoyl of 2 to 10 carbon atoms or arylcarbonyl; R.sub.1 is alkyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, aryl or arylalkyl; R.sub.2 is hydrogen; R.sub.3 is ##STR197## R.sub.4 is hydrogen, lower alkyl or arylalkyl; R.sub.7 and R.sub.8 are each independently selected as hydrogen, lower alkyl or are combined as --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 -- or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 --; m is an integer from 0 to 7; p is an integer from 1 to 3; AA.sub.n is an amino acid chain of from one to three amino acids; n is 1 or 1, 2 or 1, 2, 3; when p is 1, AA.sub.n is AA.sub.1 ; when p is 2, AA.sub.n is AA.sub.1 -AA.sub.2 ; when p is 3, AA.sub.n is AA.sub.1 -AA.sub.2 -AA.sub.3 ; AA.sub.1 is glycine or alanine; AA.sub.2 is glycine or alanine; AA.sub.3 is leucine, glutamine or isoleucine, and physiologically acceptable salts thereof. 2. A compound of claim 1 wherein R is hydrogen, R.sub.3 is ##STR198## and m is 0 to 3. 3. A compound of claim 2 wherein n is 3. 4. The compound having the name (.+-.)-N-[2-(dimethylamino)ethyl]-N.sup.2 -[2-(mercaptomethyl)-4-methyl-1-oxopentyl]glycinamide, barbituric acid (1:1) salt. 5. The compound of claim 1 having the name (.+-.)-N-[4-[(aminoiminomethyl)amino]butyl]-N.sup.2 -[2-(mercaptomethyl)-4-methyl-1-oxopentyl]glycinamide, acetate (1:1) salt. 6. The compound having the name (.+-.)-4-[[[[-2-(mercaptomethyl)-4-methyl-1-oxopentyl]amino]acetyl]amino]b utanoic acid. 7. A pharmaceutical composition for reducing the adverse effects of mammalian collagenase which comprises a compound as defined in claim 1 and a pharmaceutically acceptable carrier therefor. 8. A method for reducing the adverse effects of mammalian collagenase in a mammalian host in need thereof, which comprises administering to said mammal an effective amount of a compound as defined in claim 1. 9. A method for treating rheumatoid arthritis in a mammalian host, which comprises administering an effective amount of a compound as defined in claim 1.

Details for Patent 4,424,354

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2039-03-29