Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor ¦Ä agonists as potent anti-obesity agents in?vivo

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• 作者：Jungyeob Ham^a ; ¹ ; ² ; Hoosang Hwang^a ; ^b ; ¹ ; Euno Kim^a ; Jeong-ah Kim^a ; Sung Jin Cho^a ; Jaeyoung Ko^a ; Woojin Lee^c ; Jaehwan Lee^a ; Harish Holla^a ; Joydeep Banerjee^a ; Seokho Kim^a ; Inho Yang^a ; Hyun Joo Lee^a ; Kyoungjin Shin^a ; Hyukjae Choi^a ; Sang-Jip Nam^d ; Jungae Tak^a ; Dongyup Hahn^a ; Taekyung Oh^a ; Dong Hwan Won^a ; Tae Gu Lee^a ; Jihye Choi^a ; Mi Sun Park^a ; Chaok Seok^c ; Jungwook Chin^a ; ^b ; ^{jwchin97@snu.ac.kr} ; Heonjoong Kang^a ; ^b ; ^{hjkang@snu.ac.kr}
• 关键词：PPAR¦Ä ; Nuclear receptors ; Marine natural products ; Anti-obesity ; GW501516
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：53
• 期：Complete
• 页码：190-202
• 全文大小：1437 K

文摘

We have discovered and demonstrated the in?vitro and in?vivo PPAR¦Ä-selective activity of novel Y-shaped agonists. These compounds activated hPPAR¦Ä with EC₅₀ values between 1 and 523?nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPAR¦Ä agonists with 10⁴-fold selectivity over the other two subtypes, namely, hPPAR¦Á and hPPAR¦Ã. The PPAR¦Ä ligands 10a, 11e and 11f showed good bioavailability and in?vivo efficacy.