2-(N-acyl) and 2-N-acyl-N(6)-substituted analogues of adenosine and their affinity at the human adenosine receptors.
A series of 2-(N-acyl) and 2-(N-acyl)-N(6)-alkyladenosine analogues have been synthesized from the intermediate 2-amino-6-chloroadenosine derivatives (2b and 7) and evaluated for their affinity at the human A(1), A(2A), and A(3) receptors. We found that 2-(N-acyl) derivatives of adenosine showed relatively low affinity at A(2A) and A(3) receptors, while the N(6)-cyclopentyl substituent in 4h and 4i induced high potency [A(1) (K(i))=20.7 and 31.8 nM respectively] at the A(1) receptor and resulted therefore in increased selectivity for this subtype. The general synthetic methods and their binding studies are presented herein.
Jagtap
Prakash G
PG
Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA. pjagtap@inotekcorp.com
Chen
Zhiyu
Z
Szabó
Csaba
C
Klotz
Karl-Norbert
KN
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
D018047:Receptors, Purinergic P1; D000241:Adenosine