Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist

被引：43

作者：

Palucki, BL ^{[1
]}

Park, MK

Nargund, RP

Ye, ZX

Sebhat, IK

Pollard, PG

Kalyani, RN

Tang, R

MacNeil, T

Weinberg, DH

Vongs, A

Rosenblum, CI

Doss, GA

Miller, RR

Stearns, RA

Peng, QP

Tamvakopoulos, C

McGowan, E

Martin, WJ

Metzger, JM

Shepherd, CA

Strack, AM

MacIntyre, DE

Van der Ploeg, LHT

Patchett, AA

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Obes Res, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Drug Metab, Rahway, NJ 07065 USA

[4] Merck Res Labs, Dept Pharmacol, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 01期

关键词：

melanocortin; obesity; sexual dysfunction;

D O I：

10.1016/j.bmcl.2004.10.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：171 / 175

页数：5

共 40 条

[1] Ligands to the melanocortin receptors
Andersson, PM
Boman, A
Seifert, E
Skottner, A
Lundstedt, T
[J]. EXPERT OPINION ON THERAPEUTIC PATENTS, 2001, 11 (10) : 1583 - 1592
[2] BAKSHI RK, 2003, 25 NAT M AM CHEM SOC
[3] Bednarek MA, 2004, EXPERT OPIN THER PAT, V14, P327
[4] Selective, high affinity peptide antagonists of α-melanotropin action at human melanocortin receptor 4:: Their synthesis and biological evaluation in vitro
Bednarek, MA
MacNeil, T
Kalyani, RN
Tang, R
Van der Ploeg, LHT
Weinberg, DH
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (22) : 3665 - 3672
[5] Structure-function studies on the cyclic peptide MT-II, lactam derivative of α-melanotropin
Bednarek, MA
Silva, MV
Arison, B
MacNeil, T
Kalyani, RN
Huang, RRC
Weinberg, DH
[J]. PEPTIDES, 1999, 20 (03) : 401 - 409
[6] Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction
Diamond, LE
Earle, DC
Rosen, RC
Willett, MS
Molinoff, PB
[J]. INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, 2004, 16 (01) : 51 - 59
[7] DOSS GA, UNPUB CHEM RES TOXIC
[8] Aryl piperazine melanocortin MC4 receptor agonists
Dyck, B
Parker, J
Phillips, T
Carter, L
Murphy, B
Summers, R
Hermann, J
Baker, T
Cismowski, M
Saunders, J
Goodfellow, V
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (21) : 3793 - 3796
[9] Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency
Farooqi, IS
Yeo, GSH
Keogh, JM
Aminian, S
Jebb, SA
Butler, G
Cheetham, T
O'Rahilly, S
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (02) : 271 - 279
[10] GANTZ I, 2003, AM J PHYSIOL-ENDOC M, V284, pE486

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