Amino-substituted 1,8-naphthyridines and pyrido[2,3-d]pyrimidines: new compounds with affinity for A1- and A2-adenosine receptors.
Two novel classes of adenosine receptor (AR) antagonists, 4-amino-1,8-naphthyridines and 5-aminopyrido[2,3-d]pyrimidines, have been identified and investigated in radioligand binding assays. The compounds exhibit affinities for A1 and A2a AR of rat brain in the micromolar range. 1,8-Naphthyridines are non-selective, or somewhat selective for either A1- or A2 AR. Pyrido[2,3-d]pyrimidines are several-fold selective for A1 AR, the most potent and selective compound being 5-n-butylamino-1,3-dimethyl-1,2,3,4-tetrahydropyrido-[2,3-d]pyr imi dine-2,4-dione (12) with a Ki value of 1.8 microM at A1 AR and greater than 10-fold A1-selectivity.
Müller
C E
CE
Pharmazeutisches Institut, Universität Tübingen.
Grahner
B
B
Heber
D
D
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D066298:In Vitro Techniques; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014970:Xanthines / Q000493:pharmacokinetics
D009287:Naphthyridines; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D014970:Xanthines