Discovery of novel isoxazolines as anti-tuberculosis agents.
Nitrofuranyl isoxazolines with increased proteolytic stability over nitrofuranyl amides were designed and synthesized leading to discovery of several compounds with potent in vitro anti-tuberculosis activity. However, their in vivo activity was limited by high protein binding and poor distribution. Consequently, a series of non-nitrofuran containing isoxazolines were prepared to determine if the core had residual anti-tuberculosis activity. This led to the discovery of novel isoxazoline 12 as anti-tuberculosis agent with a MIC(90) value of 1.56microg/mL.
Tangallapally
Rajendra P
RP
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Sun
Dianqing
D
Rakesh
Budha
Nageshwar
N
Lee
Robin E B
RE
Lenaerts
Anne J M
AJ
Meibohm
Bernd
B
Lee
Richard E
RE
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D009581:Nitrofurans / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats
D000995:Antitubercular Agents; D007555:Isoxazoles; D009581:Nitrofurans