Such as 1-{[(2S,3S,5R)-2-Carboxy-3-methyl-4,4,7-trioxo-4-thia-1-azabicyclo[3.2.0]hept-3-yl]methyl}-3-methyl-1H-1,2,3-triazol-3-ium; beta-lactamase inhibitors
Inventors
Udayampalayam Palanisamy, Senthilkumar • Gnanaprakasam, Andrew • Ganapathy, Panchapakesan • Gohain, Mukut • Hariharan, Venkatasubramanian • Rajagopal, Sriram • Paul-Satyaseela, Maneesh • SINGH SOLANKI, Shakti • Devarajan, Sathishkumar
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-7687488-B2
Publication Date
2010-03-30
Expiration Date
Abstract
Novel 2-substituted methyl penam derivatives include the formula (I), their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their solvates, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them; wherein A=C or N; Het is a three- to seven-membered heterocyclic ring; R1 represents carboxylate anion, or —COOR4 where R4 represents hydrogen, carboxylic acid protecting group or a pharmaceutically acceptable salt; R2 and R3 may be same or different and independently represent hydrogen, halogen, amino, alkyl, protected amino, optionally substituted alkyl, alkenyl, alkynyl and the like; R represents substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, cycloalkyl, heterocyclyl or heterocyclylalkyl.
Core Innovation
The invention relates to 2-substituted methyl penam compounds of formula (I), including tautomeric forms, stereoisomers, pharmaceutically acceptable salts, solvates, and polymorphs. The compounds are defined by structural constraints including A=C or N and a five- to six-membered heterocyclic ring (Het), with R1 as a carboxylate anion or —COOR4, where R4 is hydrogen, a carboxylic acid protecting group, or a pharmaceutically acceptable salt.
The heterocyclic substitution pattern further constrains R2 and R3 to groups that may be same or different and may independently represent hydrogen, halogen, amino, protected amino, or optionally substituted alkyl, alkenyl, and alkynyl. The definition of R allows substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, cycloalkyl, oxo, heterocyclyl, or heterocyclylalkyl, collectively defining a class of penam compounds having specified substitution and heterocycle features.
The disclosed compounds are presented as β-lactamase inhibitors for use in combination with β-lactam antibiotics to prevent or treat bacterial infections. The invention also includes pharmaceutically acceptable compositions comprising at least one 2-substituted methyl penam compound together with a pharmaceutically acceptable carrier, and therapeutic use directed to treating a bacterial infection in a mammal by administering an antibiotic together with a compound of formula (I) and an effective amount.
Claims Coverage
The document provides two independent claims. The inventive core is the chemical structure/formula-defined penam compound class, including tautomeric forms, stereoisomers, pharmaceutically acceptable salts or compositions, with defined Het ring size and defined substitution class constraints for R1, R2, R3, and R.
2-substituted methyl penam compounds of formula (I)
A 2-substituted methyl penam compound of formula (I), including tautomeric forms, stereoisomers, pharmaceutically acceptable salts, solvates, and polymorphs, where A=C or N; Het is a five- to six-membered heterocyclic ring; R1 is a carboxylate anion or —COOR4 with R4 being hydrogen, a carboxylic acid protecting group, or a pharmaceutically acceptable salt; and R2 and R3 may be same or different and independently represent hydrogen, halogen, amino, protected amino, or optionally substituted alkyl, alkenyl, alkynyl, while R is represented by substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, cycloalkyl, oxo, heterocyclyl, or heterocyclylalkyl.
Penam compounds defined by formula substitutions including R1 carboxylate groups
A penam compound of the stated formula, including tautomeric forms, stereoisomers, pharmaceutically acceptable salts, and pharmaceutically acceptable compositions thereof, wherein R1 is a carboxylate anion or —COOR4 with R4 being hydrogen, a carboxylic acid protecting group, or a pharmaceutically acceptable salt; R2 and R3 may be same or different and may independently represent hydrogen, halogen, amino, protected amino, or optionally substituted alkyl, alkenyl, alkynyl; and R is represented by substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, cycloalkyl, oxo, heterocyclyl, or heterocyclylalkyl.
Across the independent claims, the core coverage is the chemical structure/formula-defined penam compound class, including tautomeric forms, stereoisomers, and pharmaceutically acceptable salts or compositions, with defined Het ring size and defined substitution class constraints for R1, R2, R3, and R.
Stated Advantages
The compounds are described for preventing or treating bacterial infections in combination with β-lactam antibiotics.
Biological testing reports in vitro MIC synergy improvements for the novel inhibitors versus a reference inhibitor (Tazo) across multiple Gram-negative clinical isolates and ESBL/TEM-producing strains.
Documented Applications
Use of the β-lactamase inhibitors in combination with β-lactam antibiotics for preventing or treating bacterial infections.
In vitro MIC synergy testing with Piperacillin versus Tazo across multiple Gram-negative clinical isolates and ESBL/TEM-producing strains.
Interested in licensing this patent?