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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Event Hall |
| Time |
4월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-583 |
| Subject |
Synthesis and SAR study of arylsulfonyl hydrazide derivatives as novel mPGES-1 inhibitors |
| Authors |
YoonHyoung Moon, ChangYoung Jang, Da Woon Jung, Jae Yeol Lee1,*, sunyoung Kim1, Hong bin Yoon1
Chemistry, Kyung Hee University, Korea
1Department of Chemistry, Kyung Hee University, Korea
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| Abstract |
Microsomal prostaglandin E synthase-1 (mPGES)-1 is responsible for the massive prostaglandin E2 (PGE2) formation during inflammation. Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal anti-inflammatory drugs. In order to identify potent mPGES-1 inhibitors, therefore, a series of arylsulfonyl hydrazide derivatives has been synthesized and their mPGES-1 biological activities have been disclosed in detail. Structure-activity relationship (SAR) optimization provided a few of inhibitors with moderate mPGES-1 potency and excellent PGE2 release RAW 264.7 cell potency. Among inhibitor studied, MPO-0063 provided excellent selectivity over COX-1 and COX-2. Furthermore, MPO-0063 demonstrated good metabolic stability in human liver microsomes and no significant inhibition observed in clinically relevant CYP isoforms. Additionally, MPO-0063 revealed strong in vivo efficacy in on carrageenan-induced paw edema in rats. |
| E-mail |
mss960@naver.com |
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121st General Meeting of the KCS