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A New Class of Selective COX-2 Inhibitor: Luotonin A Homologues and their Aza-analogues  

Kim, Dong-Hyeon (College of Pharmacy, Yeungnam University)
Liang, Jing-Liu (College of Pharmacy, Yeungnam University)
Oh, Joon-Seok (College of Pharmacy, Yeungnam University)
Jahng, Yurng-Dong (College of Pharmacy, Yeungnam University)
Kim, Jin-Cheul (College of Pharmacy, Yeungnam University)
Hong, Tae-Gyun (College of Pharmacy, Yeungnam University)
Hwang, Nam-Kyung (College of Pharmacy, Yeungnam University)
Chung, Hwan-Ki (College of Pharmacy, Yeungnam University)
Kim, Yun-Kyung (College of Pharmacy, Yeungnam University)
Chang, Hyeun-Wook (College of Pharmacy, Yeungnam University)
Publication Information
YAKHAK HOEJI / v.51, no.5, 2007 , pp. 313-317 More about this Journal
Abstract
A series of luotonin A homologues and their aza-analogues were prepared and evaluated their inhibitory activities on COX-1 and 2 as well as their selectivities on COX-2. The aza-analogue of dimethylene-bridged homologue of luotonin A, 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone (2b), exhibited strongest inhibitory activity against COX-1 and COX-2 dependent phase of prostaglandin $D_2$ generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with an $IC_{50}$ of 39.3 and $1.89{\mu}M$, respectively. Selectivity of 2b on COX-2 over COX-1 was 21 which implied 2b can be a potential lead for the development of selective COX-2 inhibitor.
Keywords
luotonin A; COX-2 inhibitor; bone marrow-derived mast cell; prostagladin $D_2$; 3,3'-dimethylene-2-(quinolin-2'-yl)-4(3H)-quinazolinone; 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone;
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