Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing
|Title:||Combination of thienamycin-type antibiotics with dipeptidase inhibitors|
|Abstract:||Antibacterial compositions of thienamycin-type compounds and a dipeptidase (E.C.188.8.131.52) inhibitor.|
|Inventor(s):||Kahan; Frederick M. (Scotch Plains, NJ), Kropp; Helmut (Kenilworth, NJ)|
|Assignee:||Merck & Co., Inc. (Rahway, NJ)|
|Filing Date:||Jun 24, 1985|
|Claims:||1. A method for inhibiting the dipeptidase enzyme (E.C.184.108.40.206) 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-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);
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.
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.