Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity

Silvia Galiano; Javier Ceras; Nuria Cirauqui; Silvia Pérez; Laura Juanenea; Gildardo Rivera; Ignacio Aldana; Antonio Monge

doi:10.1016/j.bmc.2007.02.049

Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity

Silvia Galiano, Javier Ceras, Nuria Cirauqui, Silvia Pérez, Laura Juanenea, Gildardo Rivera, Ignacio Aldana, Antonio Monge

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3′-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM K_i.

Original language	English
Pages (from-to)	3896-3911
Number of pages	16
Journal	Bioorganic and Medicinal Chemistry
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.bmc.2007.02.049
State	Published - 1 Jun 2007
Externally published	Yes

Keywords

Biphenylmethyl urea
MCH
MCH-R1 antagonist
Obesity

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10.1016/j.bmc.2007.02.049

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title = "Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity",

abstract = "We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3′-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM Ki.",

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T1 - Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity

AU - Galiano, Silvia

AU - Ceras, Javier

AU - Cirauqui, Nuria

AU - Pérez, Silvia

AU - Juanenea, Laura

AU - Rivera, Gildardo

AU - Aldana, Ignacio

AU - Monge, Antonio

PY - 2007/6/1

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N2 - We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3′-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM Ki.

AB - We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3′-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM Ki.

KW - Biphenylmethyl urea

KW - MCH

KW - MCH-R1 antagonist

KW - Obesity

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DO - 10.1016/j.bmc.2007.02.049

M3 - Artículo

SN - 0968-0896

VL - 15

SP - 3896

EP - 3911

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 11

ER -

Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity

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Keywords

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