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Generated: May 23, 2018

DrugPatentWatch Database Preview

Details for Patent: 4,616,038

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Title: Combination of thienamycin-type antibiotics with dipeptidase inhibitors
Abstract:Antibacterial compositions of thienamycin-type compounds and a dipeptidase (E.C. inhibitor.
Inventor(s): Kahan; Frederick M. (Scotch Plains, NJ), Kropp; Helmut (Kenilworth, NJ)
Assignee: Merck & Co., Inc. (Rahway, NJ)
Filing Date:Jun 24, 1985
Application Number:06/747,750
Claims:1. A method for inhibiting the dipeptidase enzyme (E.C. which comprises administering to an animal from 3-200 mg/kg daily of a compound of the following formula: ##STR73## wherein R.sup.2 and R.sup.3 are hydrocarbon radicals in the range respectively of 3-10 and 1-15 carbon atoms; in either one of these R.sup.2 or R.sup.3 hydrocarbon chains 1-6 hydrogens may be replaced by halogens or a nonterminal methylene may be replaced by oxygen or sulfur, including oxidized forms of the latter; additionally, a terminal hydrogen in R.sup.3 can also be replaced by hydroxyl or thiol, which may be acylated or carbamoylated; or the hydrogen can be replaced by amino, which may be derivatized as in an acylamino, ureido amidino, quanidino, or alkyl or substituted amino group, including quaternary nitrogen groupings; or, there may be replacement by acid groups such as carboxylic, phosphonic or sulfonic acid groups or esters or amides thereof, or cyano; or combinations thereof, such as a terminal amino acid grouping; and R.sup.1 is hydrogen or lower alkyl (C.sub.1-6) or dialkylaminoalkyl, or a pharmaceutically acceptable cation.

2. The method of claim 1 in which the dipeptidase inhibitor is 7-(L-2-amino-2-carboxyethylthio)-2-(2,2-dimethylcyclopropane carboxamido)-2-heptenoic acid.

3. The method of claim 1 wherein R.sup.2 is branched alkyl or cycloalkyl with a limitation that the carbon adjacent to the carbonyl cannot be tertiary.

4. The method of claim 3 wherein R.sup.3 is n-alkyl (1-9 carbons) or n-alkyl (1-9 carbons) having a terminal substituent which is a quaternary nitrogen, amine derivative or amino acid derived group.

5. The method of claim 4 wherein R.sup.2 is 2,2-dimethyl cyclopropyl or 2,2-dichlorocyclopropyl and R.sup.3 is a hydrocarbon chain of 3 to 7 carbon atoms without a terminal substituent or having a terminal substituent which trimethylammonium, amidino, guanidino or 2-amino-2-carboethylthio.

6. The method of claim 5 wherein said dipeptidase inhibitor is

Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-trimethylammonium hydroxide-2-octenoic acid inner salt;

Z-2-(2,2-dichlorocyclopropanecarboxamido)-8-trimethylammonium hydroxide-2-octenoic acid inner salt;

Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-guanidino-2-octenoic acid;

Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-guanidino-2-octenoic acid;

Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-ureido-2-octenoic acid;

Z-8-(1-2-amino-2-carboxyethylthio)-2-(2,2-dimethylcyclopropanecarboxamido)- 2-octenoic acid;

Z-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid (racemic and dextrorotatory forms);

Z-2-(2,2-dichlorcyclopropanecarboxamido)-2-octenoic acid;

7-(L-2-amino-2-carboxyethylthio)-2-(2,2-dimethylcyclopropanecarboxamido)-2- heptenoic acid; or

6-(L-2-amino-2-carboxyethythio)-2-(2,2-dimethylcyclopropanecarboxamido)-2-h exenoic acid.

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Serving hundreds of leading biopharmaceutical companies globally:

Fish and Richardson
Queensland Health
Express Scripts

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