[11C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin Gene-Related Peptide Receptor

被引：19

作者：

Bell, Ian M. ^{[1
]}

Gallicchio, Steven N. ^{[1
]}

Stump, Craig A. ^{[1
]}

Bruno, Joseph G. ^{[4
]}

Fan, Hong ^{[3
]}

Gantert, Liza T. ^{[3
]}

Hostetler, Eric D. ^{[3
]}

Kemmerer, Amanda L. ^{[4
]}

McWherter, Melody ^{[1
]}

Moore, Eric L. ^{[2
]}

Mosser, Scott D. ^{[4
]}

Purcell, Mona L. ^{[3
]}

Riffel, Kerry ^{[3
]}

Salvatore, Christopher A. ^{[2
]}

Sanabria-Bohorquez, Sandra ^{[3
]}

Staas, Donnette D. ^{[1
]}

White, Rebecca B. ^{[6
]}

Williams, Mangay ^{[3
]}

Zartman, C. Blair ^{[1
]}

Cook, Jacquelynn J. ^{[3
]}

Hargreaves, Richard J. ^{[5
]}

Kane, Stefanie A. ^{[2
]}

Graham, Samuel L. ^{[1
]}

Selnick, Harold G. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Pain & Migraine, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Imaging, West Point, PA 19486 USA

[4] Merck Res Labs, Dept In Vitro Pharmacol, West Point, PA 19486 USA

[5] Merck Res Labs, Dept Neurosci & Ophthalmol, West Point, PA 19486 USA

[6] Merck Res Labs, Dept Pharmacokinet Pharmacodynam & Drug Metab, West Point, PA 19486 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 09期

关键词：

MK-4232; calcitonin gene-related peptide receptor; positron emission tomography; CGRP; ANTAGONIST; MIGRAINE; POTENT; DISCOVERY;

D O I：

10.1021/ml400199p

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Rational modification of the potent calcitonin gene-related peptide (CGRP) receptor antagonist MK-3207 led to a series of analogues with enhanced CNS penetrance and a convenient chemical handle for introduction of a radiolabel. A number of C-11-tracers were synthesized and evaluated in vivo, leading to the identification of [C-11](8) ([C-11]MK-4232), the first positron emission tomography tracer for the CGRP receptor.

引用

页码：863 / 868

页数：6

共 20 条

[1] MK-8825: A potent and selective CGRP receptor antagonist with good oral activity in rats [J].

Bell, Ian M. ;

Stump, Craig A. ;

Gallicchio, Steven N. ;

Staas, Donnette D. ;

Zartman, C. Blair ;

Moore, Eric L. ;

Sain, Nova ;

Urban, Mark ;

Bruno, Joseph G. ;

Calamari, Amy ;

Kemmerer, Amanda L. ;

Mosser, Scott D. ;

Fandozzi, Christine ;

White, Rebecca B. ;

Zrada, Matthew M. ;

Selnick, Harold G. ;

Graham, Samuel L. ;

Vacca, Joseph P. ;

Kane, Stefanie A. ;

Salvatore, Christopher A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (12) :3941-3945

[2] Discovery of MK-3207: A Highly Potent, Orally Bioavailable CGRP Receptor Antagonist [J].

Bell, Ian M. ;

Gallicchio, Steven N. ;

Wood, Michael R. ;

Quigley, Amy G. ;

Stump, Craig A. ;

Zartman, C. Blair ;

Fay, John F. ;

Li, Chi-Chung ;

Lynch, Joseph J. ;

Moore, Eric L. ;

Mosser, Scott D. ;

Prueksaritanont, Thomayant ;

Regan, Christopher P. ;

Roller, Shane ;

Salvatore, Christopher A. ;

Kane, Stefanie A. ;

Vacca, Joseph P. ;

Selnick, Harold G. .

ACS MEDICINAL CHEMISTRY LETTERS, 2010, 1 (01) :24-29

[3] BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: Results from a phase II study [J].

Diener, Hans-Christoph ;

Barbanti, Piero ;

Dahloef, Carl ;

Reuter, Uwe ;

Habeck, Julia ;

Podhorna, Jana .

CEPHALALGIA, 2011, 31 (05) :573-584

[4] Inhibition of calcitonin gene-related peptide function: A promising strategy for treating migraine [J].

Durham, Paul L. .

HEADACHE, 2008, 48 (08) :1269-1275

[5]

Eckelman WC., 1979, Principles of radiopharmacology, P251

[6] CGRP Receptor Antagonism and Migraine [J].

Edvinsson, Lars ;

Ho, Tony W. .

NEUROTHERAPEUTICS, 2010, 7 (02) :164-175

[7] Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine [J].

Hewitt, David J. ;

Aurora, Sheena K. ;

Dodick, David W. ;

Goadsby, Peter J. ;

Ge, Yang ;

Bachman, Robert ;

Taraborelli, Donna ;

Fan, Xiaoyin ;

Assaid, Christopher ;

Lines, Christopher ;

Ho, Tony W. .

CEPHALALGIA, 2011, 31 (06) :712-722

[8] CGRP and its receptors provide new insights into migraine pathophysiology [J].

Ho, Tony W. ;

Edvinsson, Lars ;

Goadsby, Peter J. .

NATURE REVIEWS NEUROLOGY, 2010, 6 (10) :573-582

[9] Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial [J].

Ho, Tony W. ;

Ferrari, Michel D. ;

Dodick, David W. ;

Galet, Vince ;

Kost, James ;

Fan, Xiaoyin ;

Leibensperger, Heather ;

Froman, Samar ;

Assaid, Christopher ;

Lines, Christopher ;

Koppen, Hille ;

Winner, Paul K. .

LANCET, 2008, 372 (9656) :2115-2123

[10]

Hostetler E., 2009, 6 ANN WORLD MOL IM C

← 1 2 →