Synthesis and in vitro binding studies of substituted piperidine naphthamides. Part I: Influence of the substitution on the basic nitrogen and the position of the amide on the affinity for D-2L, D-4.2, and 5-HT2A receptors
[en] A series of 1- and 2-naphthamides has been prepared and tested for in vitro binding to D-2L, D-4.2, and 5-HT2A receptors. Different compounds display selectivity for D-4.2 and 5-HT2A receptors versus D-2L receptors. N-(1-Arylalkyl-piperidin-4-yl) carboxamides have higher affinities than the corresponding N-(4-arylalkylamino-piperidin-1-yl) carboxamide analogues. A benzyl moiety in position 1 of the piperidine in the 2-naphthamide series (2) appears to be the best choice for a favorable interaction with D-4.2 and 5-HT2A receptors. Increasing the linker length between the phenyl ring and the basic nitrogen led to a decreased affinity for these receptors. In the 1-naphthamide series, the most potent D-4.2 ligand (7) possesses a phenylpropyl moiety while its affinity for 5-HT2A receptors is strongly reduced. All compounds with significant affinity for D-4.2 and 5-HT2A receptors were antagonists. (c) 2007 Elsevier Ltd. All rights reserved.
Liégeois, Jean-François ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
Synthesis and in vitro binding studies of substituted piperidine naphthamides. Part I: Influence of the substitution on the basic nitrogen and the position of the amide on the affinity for D-2L, D-4.2, and 5-HT2A receptors
Publication date :
15 March 2007
Journal title :
Bioorganic and Medicinal Chemistry Letters
ISSN :
0960-894X
eISSN :
1464-3405
Publisher :
Pergamon-Elsevier Science Ltd, Oxford, United Kingdom
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Wong A.H.C., and Van Tol H.H.M. Neurosci. Biobehav. Rev. 27 (2003) 269
Ellenbroek B.A., and Liégeois J.-F. CNS Drug Rev. 9 (2003) 41
Liégeois J.-F., Bruhwyler J., Damas J., Nguyen T.P., Chleide E., Mercier M., Rogister F., and Delarge J. J. Med. Chem. 36 (1993) 2107
Liégeois J.-F., Rogister F., Bruhwyler J., Damas J., Nguyen T.P., Inarejos M.-O., Chleide E., Mercier M., and Delarge J. J. Med. Chem. 37 (1994) 519
Roth B.L., Sheffler D.L., and Kroeze W.K. Nature Rev. Drug Discov. 3 (2004) 353
Van Tol H.H.M., Bunzow J.R., Guan H.C., Sunahara R.K., Seeman P., Niznik H.B., and Civelli O. Nature 350 (1991) 610
Seeman P., Corbett R., and Van Tol H.H.M. Neuropsychopharmacology 16 (1997) 93
Kotecha S.A., Oak J.N., Jackson M.F., Perez Y., Orser B.A., Van Tol H.H.M., and MacDonald J.F. Neuron 35 (2002) 1111
Rubinstein M., Cepeda C., Hurst R.S., Flores-Hernandez J., Ariano M.A., Falzone T.L., Kozell L.B., Meshul C.K., Bunzow J.R., Low M.J., Levine M.S., and Grandy D.K. J. Neurosci. 21 (2001) 3756
Truffinet P., Tamminga C.A., Fabre L.F., Meltzer H.Y., Riviere M.E., and Papillon-Downey C. Am. J. Psychiatry 156 (1999) 419
Tarazi F.I., Zhang K., and Baldessarini R.J. J. Pharmacol. Exp. Ther. 297 (2001) 711
Tarazi F.I., Zhang K., and Baldessarini R.J. Psychopharmacology 161 (2002) 263
Petcher T.J., and Weber H.-P. J. Chem. Soc., Perkin Trans. II (1976) 1415
Liégeois J.-F., Eyrolles L., Ellenbroek B.A., Lejeune C., Carato P., Bruhwyler J., Géczy J., Damas J., and Delarge J. J. Med. Chem. 45 (2002) 5136
Cheng Y.-C., and Prusoff W.H. Biochem. Pharmacol. 22 (1973) 3099
Jaen J.C., Caprathe B.W., Pugsley T.A., Wise L.D., and Hyacinth Akunne H. J. Med. Chem. 36 (1993) 3929
GTP-γ32S functional assay using membranes of cells stably expressing the human D4 receptor. Membrane preparations were preincubated in a total volume of 300 μl for 25 min at 30 °C in assay buffer (50 mM HEPES, 100 mM NaCl, 4 mM MgCl2, 1 mM EDTA, 100 mg/l BSA, 100 mg/l ascorbic acid, pH 7.4 (adjusted with NaOH), and 20 μM GDP) in the presence 5 μM of the test compounds and 500 nM dopamine for coapplications. GTP-γ35S was added for a final concentration of 300 pM and the incubation was continued for 60 min. The membranes were harvested on type-B glass fiber filters and washed with ice-cold wash buffer (50 mM HEPES, 4 mM MgCl2, pH 7.4, adjusted with KOH). The experiments were run twice with each data point measured in triplicate.
Davies M.A., Setola V., Strachan R.T., Sheffler D.J., Salay E., Hufeisen S.J., and Roth B.L. Pharmacogenomics J. (2005) eFirst
Boyfield I., Brown T.H., Coldwell M.C., Cooper D.G., Hadley M.S., Hagan J.J., Healy M.A., Johns A., King R.J., Middlemiss D.N., Nash D.J., Riley G.J., Scott E.E., Smith S.A., and Stemp G. J. Med. Chem. 39 (1996) 1946
Högberg T. Drugs Future 16 (1991) 333
Arora J., Bordeleau M., Dube L., Jarvie K., Mazzocco L., Peragine J., Tehim A., and Egle I. Biorg. Med. Chem. Lett. 15 (2005) 5253
Kapur S., and Seeman P. J. Psychiatry Neurosci. 25 (2000) 161
Kapur S., Zipursky R., Jones C., Shammi C.S., Remington G., and Seeman P. Arch. Gen. Psychiatry 57 (2000) 553
Scuvée-Moreau J., Boland A., Graulich A., Van Overmeire L., D'hoedt D., Graulich-Lorge F., Thomas E., Abras A., Stocker M., Liégeois J.-F., and Seutin V. Br. J. Pharmacol. 143 (2004) 753
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.