AMP deaminase inhibitors. 3. SAR of 3-(carboxyarylalkyl)coformycin aglyconanalogues

N3-Substituted coformycin aglycon analogues with improved AMP deaminase (AM PDA) inhibitory potency are described. Replacement of the 5-carboxypentyl s ubstituent in the lead AMPDA inhibitor 3-(5-carboxypentyl)-3,6,7,8-tetrahyd roimidazo[4,5-d][1,3]diazepin-8-ol (2) described in the previous article wi th various carboxyarylalkyl groups resulted in compounds with 10-100-fold i mproved AMPDA inhibitory potencies. The optimal N3 substituent had m-carbox yphenyl with a two-carbon alkyl tether. For example, 3-[2-(3-carboxy-5-ethy lphenyl)-ethyl]-3,6,7,8-tetrahydroimidazo[4,5-d] [1,3]diazepin-8-ol (43g) i nhibited human AMPDA with a K-i = 0.06 mu M. The compounds within the serie s also exhibited >1000-fold specificity for AMPDA relative to adenosine dea minase.