9-Ethyladenine derivatives as adenosine receptor antagonists: 2-
and 8-substitution results in distinct selectivities
K. Klotz, S. Kachler, C. Lambertucci, S. Vittori, R. Volpini, and G. Cristalli. Naunyn Schmiedebergs Arch Pharmacol, 367 (6):
629-34(June 2003)Klotz, Karl-Norbert Kachler, Sonja Lambertucci, Catia Vittori, Sauro
Volpini, Rosaria Cristalli, Gloria Research Support, Non-U.S. Gov't
Germany Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs
Arch Pharmacol. 2003 Jun;367(6):629-34. Epub 2003 May 7..
Abstract
9-Ethyladenine was used as the basis for a series of non-xanthine
adenosine receptor antagonists at human adenosine receptors. The
adenine-based compounds were substituted in 2- or 8-position with
a variety of side chains including some aryl or arylalkynyl groups
previously tested as 2-substituents in adenosine and 5'-N-ethylcarboxamidoadenosine
(NECA) for their effect on agonist affinity. The affinity of the
novel compounds was tested in radioligand binding assays (A1, A2A
and A3) and inhibition of NECA-stimulated adenylyl cyclase activity
(A2B) in membranes prepared from CHO cells stably transfected with
the respective human receptor subtype. High affinity antagonists
were identified for A1 (9-ethyl-8-phenyl-9H-adenine, compound 2;
6-(1-butylamino)-9-ethyl-8-phenyl-9H-purine, compound 3), A2A (8-ethoxy-9-ethyladenine;
compound 8) and A3 (9-ethyl-8-phenylethynyl-9H-adenine, compound
5) with selectivities versus other receptor subtypes in the range
of 10 to 600. These results demonstrate that adenine is a useful
template for further development of high-affinity antagonists with
distinct receptor selectivity profiles.
%0 Journal Article
%1 Klotz2003
%A Klotz, K. N.
%A Kachler, S.
%A Lambertucci, C.
%A Vittori, S.
%A Volpini, R.
%A Cristalli, G.
%D 2003
%J Naunyn Schmiedebergs Arch Pharmacol
%K & Adenine/*analogs Animals CHO Cricetinae Humans P1/*antagonists Purinergic Relationship Structure-Activity derivatives/*chemistry/*pharmacology inhibitors/chemistry/physiology Receptor Cell
%N 6
%P 629-34
%T 9-Ethyladenine derivatives as adenosine receptor antagonists: 2-
and 8-substitution results in distinct selectivities
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12734636
%V 367
%X 9-Ethyladenine was used as the basis for a series of non-xanthine
adenosine receptor antagonists at human adenosine receptors. The
adenine-based compounds were substituted in 2- or 8-position with
a variety of side chains including some aryl or arylalkynyl groups
previously tested as 2-substituents in adenosine and 5'-N-ethylcarboxamidoadenosine
(NECA) for their effect on agonist affinity. The affinity of the
novel compounds was tested in radioligand binding assays (A1, A2A
and A3) and inhibition of NECA-stimulated adenylyl cyclase activity
(A2B) in membranes prepared from CHO cells stably transfected with
the respective human receptor subtype. High affinity antagonists
were identified for A1 (9-ethyl-8-phenyl-9H-adenine, compound 2;
6-(1-butylamino)-9-ethyl-8-phenyl-9H-purine, compound 3), A2A (8-ethoxy-9-ethyladenine;
compound 8) and A3 (9-ethyl-8-phenylethynyl-9H-adenine, compound
5) with selectivities versus other receptor subtypes in the range
of 10 to 600. These results demonstrate that adenine is a useful
template for further development of high-affinity antagonists with
distinct receptor selectivity profiles.
@article{Klotz2003,
abstract = {9-Ethyladenine was used as the basis for a series of non-xanthine
adenosine receptor antagonists at human adenosine receptors. The
adenine-based compounds were substituted in 2- or 8-position with
a variety of side chains including some aryl or arylalkynyl groups
previously tested as 2-substituents in adenosine and 5'-N-ethylcarboxamidoadenosine
(NECA) for their effect on agonist affinity. The affinity of the
novel compounds was tested in radioligand binding assays (A1, A2A
and A3) and inhibition of NECA-stimulated adenylyl cyclase activity
(A2B) in membranes prepared from CHO cells stably transfected with
the respective human receptor subtype. High affinity antagonists
were identified for A1 (9-ethyl-8-phenyl-9H-adenine, compound 2;
6-(1-butylamino)-9-ethyl-8-phenyl-9H-purine, compound 3), A2A (8-ethoxy-9-ethyladenine;
compound 8) and A3 (9-ethyl-8-phenylethynyl-9H-adenine, compound
5) with selectivities versus other receptor subtypes in the range
of 10 to 600. These results demonstrate that adenine is a useful
template for further development of high-affinity antagonists with
distinct receptor selectivity profiles.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Klotz, K. N. and Kachler, S. and Lambertucci, C. and Vittori, S. and Volpini, R. and Cristalli, G.},
biburl = {https://www.bibsonomy.org/bibtex/2d0855464c708f54d431850036c9ec9af/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {458609aa254dc7a554565f43417850ba},
intrahash = {d0855464c708f54d431850036c9ec9af},
issn = {0028-1298 (Print) 0028-1298 (Linking)},
journal = {Naunyn Schmiedebergs Arch Pharmacol},
keywords = {& Adenine/*analogs Animals CHO Cricetinae Humans P1/*antagonists Purinergic Relationship Structure-Activity derivatives/*chemistry/*pharmacology inhibitors/chemistry/physiology Receptor Cell},
month = Jun,
note = {Klotz, Karl-Norbert Kachler, Sonja Lambertucci, Catia Vittori, Sauro
Volpini, Rosaria Cristalli, Gloria Research Support, Non-U.S. Gov't
Germany Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs
Arch Pharmacol. 2003 Jun;367(6):629-34. Epub 2003 May 7.},
number = 6,
pages = {629-34},
shorttitle = {9-Ethyladenine derivatives as adenosine receptor antagonists: 2- and
8-substitution results in distinct selectivities},
timestamp = {2010-12-14T18:20:39.000+0100},
title = {9-Ethyladenine derivatives as adenosine receptor antagonists: 2-
and 8-substitution results in distinct selectivities},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12734636},
volume = 367,
year = 2003
}