Abstract
Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs exert their activities via specific seven-transmembrane, G protein-coupled receptors. To date two receptor subtypes, endothelin A (ETA) and endothelin B (ET B), have been identified and cloned. A literature survey revealed that a number of compounds that bind ET receptors with affinity and selectivity are known, nevertheless these compounds belong only to few chemical classes. The aim of this work is the identification of an "hit compound" with novel chemical structure endowed with reasonable ET affinity and selectivity. Accordingly, new variously substituted 2-carboxamido-3-carboxythiophene derivatives (29-52) were synthesized. These compounds were tested for their ability to inhibit ETs binding in radioligand binding assay using CHO cells stably expressing human ETA and ETB receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 711-720 |
| Number of pages | 10 |
| Journal | Farmaco |
| Volume | 60 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2005 |
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Keywords
- 2-Carboxamido-3-carboxythiophene derivatives
- 4,5,6,7-Tetrahydrothieno[2,3-c]pyridine
- Endothelin receptors
- G Protein-coupled receptors
- Hypertension
ASJC Scopus subject areas
- Drug Discovery
- Pharmaceutical Science
Cite this
A facile synthesis of new 2-carboxamido-3-carboxythiophene and 4,5,6,7-tetrahydro-2-carboxamido-3-carboxythieno[2,3-c]pyridine derivatives as potential endothelin receptors ligands. / Pittalà, Valeria; Modica, Maria; Romeo, Giuseppe; Materia, Luisa; Salerno, Loredana; Siracusa, Mariangela; Cagnotto, Alfredo; Mereghetti, Ilario; Russo, Filippo.
In: Farmaco, Vol. 60, No. 9, 09.2005, p. 711-720.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A facile synthesis of new 2-carboxamido-3-carboxythiophene and 4,5,6,7-tetrahydro-2-carboxamido-3-carboxythieno[2,3-c]pyridine derivatives as potential endothelin receptors ligands
AU - Pittalà, Valeria
AU - Modica, Maria
AU - Romeo, Giuseppe
AU - Materia, Luisa
AU - Salerno, Loredana
AU - Siracusa, Mariangela
AU - Cagnotto, Alfredo
AU - Mereghetti, Ilario
AU - Russo, Filippo
PY - 2005/9
Y1 - 2005/9
N2 - Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs exert their activities via specific seven-transmembrane, G protein-coupled receptors. To date two receptor subtypes, endothelin A (ETA) and endothelin B (ET B), have been identified and cloned. A literature survey revealed that a number of compounds that bind ET receptors with affinity and selectivity are known, nevertheless these compounds belong only to few chemical classes. The aim of this work is the identification of an "hit compound" with novel chemical structure endowed with reasonable ET affinity and selectivity. Accordingly, new variously substituted 2-carboxamido-3-carboxythiophene derivatives (29-52) were synthesized. These compounds were tested for their ability to inhibit ETs binding in radioligand binding assay using CHO cells stably expressing human ETA and ETB receptors.
AB - Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs exert their activities via specific seven-transmembrane, G protein-coupled receptors. To date two receptor subtypes, endothelin A (ETA) and endothelin B (ET B), have been identified and cloned. A literature survey revealed that a number of compounds that bind ET receptors with affinity and selectivity are known, nevertheless these compounds belong only to few chemical classes. The aim of this work is the identification of an "hit compound" with novel chemical structure endowed with reasonable ET affinity and selectivity. Accordingly, new variously substituted 2-carboxamido-3-carboxythiophene derivatives (29-52) were synthesized. These compounds were tested for their ability to inhibit ETs binding in radioligand binding assay using CHO cells stably expressing human ETA and ETB receptors.
KW - 2-Carboxamido-3-carboxythiophene derivatives
KW - 4,5,6,7-Tetrahydrothieno[2,3-c]pyridine
KW - Endothelin receptors
KW - G Protein-coupled receptors
KW - Hypertension
UR - http://www.scopus.com/inward/record.url?scp=24944536619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24944536619&partnerID=8YFLogxK
U2 - 10.1016/j.farmac.2005.06.005
DO - 10.1016/j.farmac.2005.06.005
M3 - Article
C2 - 16039654
AN - SCOPUS:24944536619
VL - 60
SP - 711
EP - 720
JO - Farmaco
JF - Farmaco
SN - 0014-827X
IS - 9
ER -