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Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity.

Abstract：

:We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

He S,Ye Z,Dobbelaar PH,Bakshi RK,Hong Q,Dellureficio JP,Sebhat IK,Guo L,Liu J,Jian T,Lai Y,Franklin CL,Reibarkh M,Holmes MA,Weinberg DH,MacNeil T,Tang R,Tamvakopoulos C,Peng Q,Miller RR,Stearns RA,Chen HY,Chen

doi

10.1016/j.bmcl.2010.09.049

subject

Has Abstract

pub_date

2010-11-15 00:00:00

pages

6524-32

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01350-8

journal_volume

20

pub_type

杂志文章

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