Novel l-adenosine analogs as cardioprotective agents

Two l-nucleosides, l-3'-amino-3'-deoxy-N(6)-dimethyladenosine (l-3'-ADMdA) 1, previously synthesized in our laboratory, and the novel l-3'-amino-3'-deoxy-N(6)-methyladenosine-5'-N-methyluronamide (l-3'-AM-MECA) 2 were evaluated in an ischemia/reperfusion model on Langendorff perfused mouse heart. l-3'-ADMdA 1 was found to enhance functional recovery from ischemia (32.2+/-3.7cm H(2)O/s % rate pressure product, compared to 21.3+/-1.4 for the control and 30.7+/-3.4 for adenosine) and increase the time to onset of ischemic contracture (14.5+/-0.9min, compared to 10.5+/-1.0min for the control and 13.6+/-0.6min for adenosine) comparable to adenosine. Consistent with the functional recovery data, decreased infarction area was seen in the case of 1 (19.1+/-8.4, compared to 40.5+/-7.2% for the control and 11.5+/-2.1% for adenosine). In contrast, l-3'-AM-MECA 2 did not show significant functional recovery, increased onset of contracture, nor decreased infarction area compared to control. Unlike adenosine, neither 1 nor 2 induced cardiac standstill in mouse heart.