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.
Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA. pjagtap@inotekcorp.com
Prakash G
PG
Jagtap
Zhiyu
Z
Chen
Csaba
C
Szabó
Karl-Norbert
KN
Klotz
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