Tricyclic benzoxaborole compound, preparation method and use thereof
Inventors
Kim, Soon-Hoe • Im, Weon-Bin • Ha, Seung-Bum • Park, Jung-Sang • Kim, Mi-Yeon • Choi, Sung-Hak • Sung, Hyun-Jung
Assignees
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Publication Number
US-9676796-B2
Publication Date
2017-06-13
Expiration Date
Abstract
The present invention relates to a novel tricyclic benzoxaborole derivative, a preparation method thereof, and use of antibiotics pharmaceutical composition including the same as an active ingredient.
Core Innovation
The disclosure relates to a novel tricyclic benzoxaborole compound represented by Chemical Formula 1, including isomers and pharmaceutically acceptable salts. The disclosed scope specifically includes stereoisomeric forms and hydrochloride salts of compounds such as (7-methyl-7,8-dihydro-2H-1,6,9-trioxa-9a-borabenzo[cd]azulen-2-yl)methanamine and related chiral members.
The problem described is the need for antibacterial agents effective against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria and carbapenem-resistant Gram-negative bacteria. The disclosure ties the compound series to OBORT (Oxaborole t-RNA trapping) and to target interaction involving leucyl t-RNA synthetase and a t-RNA editing domain, and links the disclosed hydrochloride salts to antibacterial evaluation against carbapenem-resistant Acinetobacter baumannii.
The disclosure further states antibiotic pharmaceutical compositions for Gram-negative bacteria that use the tricyclic benzoxaborole compound(s) as active ingredients. Therapeutic and preventive use is described by administering to a mammal a therapeutically or prophylactically effective amount of a composition comprising the Chemical Formula 1 compound, or an isomer or pharmaceutically acceptable salt.
Claims Coverage
The independent claims are directed to three inventive features: a Chemical Formula 1 tricyclic benzoxaborole compound class defined by isomers and pharmaceutically acceptable salts, a pharmaceutical composition using that compound class for antibiotic activity against Gram-negative bacteria, and a method of treating Gram-negative bacterial infection in a mammal by administering a therapeutically or prophylactically effective amount of a composition containing the Chemical Formula 1 compound class.
Chemical Formula 1 tricyclic benzoxaborole scaffold with isomers and pharmaceutically acceptable salts
A tricyclic benzoxaborole compound represented by Chemical Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof.
Antibiotic pharmaceutical composition for Gram-negative bacteria
A pharmaceutical composition comprising a tricyclic benzoxaborole compound represented by Chemical Formula 1, or an isomer or pharmaceutically acceptable salt thereof, as an active ingredient providing antibiotic activity against Gram-negative bacteria.
Treating Gram-negative bacterial infection in a mammal by administering a therapeutically or prophylactically effective amount
A method of treating Gram-negative bacterial infection in a mammal comprising administering to the mammal a composition comprising a therapeutically or prophylactically effective amount of a tricyclic benzoxaborole compound represented by Chemical Formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof.
The claim coverage centers on the Chemical Formula 1 tricyclic benzoxaborole compound class defined by isomers and pharmaceutically acceptable salts, on its use in a pharmaceutical composition with antibiotic activity against Gram-negative bacteria, and on a mammalian treatment or prophylaxis method based on administering a therapeutically or prophylactically effective amount of such a composition.
Stated Advantages
Antibiotic activity against Gram-negative bacteria.
Treatment and prophylaxis of Gram-negative bacterial infection in a mammal.
Effective targeting is associated with OBORT (Oxaborole t-RNA trapping) involving leucyl t-RNA synthetase and a t-RNA editing domain.
Superior antibacterial activity versus reference/control compounds, including meropenem, in in vivo mouse systemic infection results and in vitro MIC testing.
Documented Applications
Antibiotic use against Gram-negative bacteria using a pharmaceutical composition comprising a Chemical Formula 1 tricyclic benzoxaborole compound, or isomer or pharmaceutically acceptable salt.
Treatment and prophylactic use for Gram-negative bacterial infection in a mammal by administering a composition comprising a therapeutically or prophylactically effective amount of the Chemical Formula 1 tricyclic benzoxaborole compound, or isomer or pharmaceutically acceptable salt.
Activity asserted for Gram-negative bacteria including multidrug- and carbapenem-resistant Gram-negative bacteria, including carbapenem-resistant Acinetobacter baumannii.
In vitro and in vivo evaluation of the disclosed tricyclic benzoxaborole hydrochloride salts as antibacterial agents, with emphasis on carbapenem-resistant Acinetobacter baumannii.
Treatment of Gram-negative bacterial infection in a mammal via administering a tricyclic benzoxaborole composition, supported by mouse systemic infection model results.
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