TY - JOUR
T1 - Medicinal chemistry of the A 3 adenosine receptor
AU - Jacobson, Kenneth A.
AU - Tosh, Dilip K.
AU - Gao, Zhan Guo
AU - Yu, Jinha
AU - Suresh, Rama R.
AU - Rao, Harsha
AU - Romagnoli, Romeo
AU - Baraldi, Pier Giovanni
AU - Aghazadeh Tabrizi, Mojgan
N1 - Publisher Copyright:
© Springer Nature Switzerland AG 2018.
PY - 2018
Y1 - 2018
N2 - Numerous structure-activity relationship (SAR) studies of ligands of the A 3 adenosine receptor (AR) have generated selective agonists, antagonists, partial agonists, and allosteric modulators. The efficacy of nucleoside agonists may be reduced, while retaining affinity, by successive structural changes. Subnanomolar affinity and selectivity of >10,000-fold have been achieved for various compound classes, but often with a pronounced species dependence, especially for diverse heterocyclic antagonists. Two prototypical A 3 AR agonists, IB-MECA and Cl-IB-MECA, are being evaluated clinically for treating autoimmune inflammatory disorders and liver diseases. The design of A 3 AR orthosteric ligands is now largely guided by computational approaches, in which the receptor is modeled by homology to X-ray structures of the A 2A AR and other G protein-coupled receptors (GPCRs). Thus, we have amassed a large body of data concerning the relationship of receptor structure and function and have supported many of the hypotheses generated with experimental data.
AB - Numerous structure-activity relationship (SAR) studies of ligands of the A 3 adenosine receptor (AR) have generated selective agonists, antagonists, partial agonists, and allosteric modulators. The efficacy of nucleoside agonists may be reduced, while retaining affinity, by successive structural changes. Subnanomolar affinity and selectivity of >10,000-fold have been achieved for various compound classes, but often with a pronounced species dependence, especially for diverse heterocyclic antagonists. Two prototypical A 3 AR agonists, IB-MECA and Cl-IB-MECA, are being evaluated clinically for treating autoimmune inflammatory disorders and liver diseases. The design of A 3 AR orthosteric ligands is now largely guided by computational approaches, in which the receptor is modeled by homology to X-ray structures of the A 2A AR and other G protein-coupled receptors (GPCRs). Thus, we have amassed a large body of data concerning the relationship of receptor structure and function and have supported many of the hypotheses generated with experimental data.
KW - A adenosine receptors
KW - A agonists
KW - A allosteric modulators
KW - A antagonists
KW - Structure-activity relationship
UR - http://www.scopus.com/inward/record.url?scp=85058224986&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-90808-3_7
DO - 10.1007/978-3-319-90808-3_7
M3 - Article
AN - SCOPUS:85058224986
SN - 1048-6909
VL - 34
SP - 169
EP - 198
JO - Receptors
JF - Receptors
ER -