کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1361270 | 981460 | 2012 | 4 صفحه PDF | دانلود رایگان |
Thirty two novel isoniazid analogues were prepared by one-pot three component condensations of isoniazid (INH), 3-mercaptopropionic acid and various aryl/heteroaryl aldehydes. The synthesized compounds were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37Rv (MTB) and cytotoxicity. Among the compounds, compound N-(2-(4-(benzyloxy) phenyl)-4-oxo-1,3-thiazinan-3-yl) isonicotinamide (17) inhibited MTB with MIC of 0.12 μM and was three times more potent than INH. The main pharmacokinetic parameters after intravenous administration (10 mg/kg body weight) in male Wistar rats viz. t½, Kel, mean plasma clearance and mean volume of distribution were found to be 1.14 ± 0.20 h, 0.62 ± 0.10 h−1, 22.48 ± 0.16 mL/kg/min and 1.99 ± 0.49 L, respectively. The systemic absorption was slow after oral administration (50 mg/kg body weight). The peak plasma concentration was found to be 1.31 ± 0.06 μg/mL attained in 3 h. The bioavailability was found to be 16.7%.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 8, 15 April 2012, Pages 2764–2767