Synthesis and structure-activity relationships of novel dipeptides and reduced dipeptides as ligands for melanocortin subtype-4 receptor.
A series of benzylic piperazines (e.g., 4 and 5) attached to an 'address element', the dipeptide H-D-Tic-D-p-Cl-Phe-OH, 3 has been identified as ligands for the melanocortin subtype-4 receptor (MC4R). We describe herein the structure-activity relationship (SAR) studies on the N-terminal residue of the 'address element'. Several novel dipeptides and reduced dipeptides with high MC4R binding affinities and selectivity emerged from this SAR study.
Shi
Qing
Q
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. shi_qing@lilly.com
Ornstein
Paul L
PL
Briner
Karin
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Richardson
Timothy I
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Arnold
Macklin B
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Backer
Ryan T
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Buckmaster
Jennifer L
JL
Canada
Emily J
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Doecke
Christopher W
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Hertel
Larry W
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Honigschmidt
Nick
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Hsiung
Hansen M
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Husain
Saba
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Kuklish
Steve L
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Martinelli
Michael J
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Mullaney
Jeffrey T
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O'Brien
Thomas P
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Reinhard
Matt R
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Rothhaar
Roger
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Shah
Jikesh
J
Wu
Zhipei
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Xie
Chaoyu
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Zgombick
John M
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Fisher
Matthew J
MJ
D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4 / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004151:Dipeptides; D008024:Ligands; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4