Selective A1-adenosine receptor antagonists identified using yeast Saccharomyces cerevisiae functional assays

R M Campbell; C Cartwright; W Chen; Y Chen; E Duzic; J M Fu; M Loveland; R Manning; B McKibben; C M Pleiman; L Silverman; J Trueheart; D R Webb; V Wilkinson; D J Witter; X Xie; A L Castelhano

doi:10.1016/s0960-894x(99)00398-4

Selective A1-adenosine receptor antagonists identified using yeast Saccharomyces cerevisiae functional assays

Bioorg Med Chem Lett. 1999 Aug 16;9(16):2413-8. doi: 10.1016/s0960-894x(99)00398-4.

Authors

R M Campbell¹, C Cartwright, W Chen, Y Chen, E Duzic, J M Fu, M Loveland, R Manning, B McKibben, C M Pleiman, L Silverman, J Trueheart, D R Webb, V Wilkinson, D J Witter, X Xie, A L Castelhano

Affiliation

¹ Cadus Pharmaceutical Corporation, Tarrytown, NY 10591, USA.

PMID: 10476879
DOI: 10.1016/s0960-894x(99)00398-4

Abstract

Evaluation of a biased "library" of pyrrolo[2,3-d]pyrimidines using yeast-based functional assays expressing human A1- and A2a-adenosine receptors, led to the A1 selective antagonist 4b. A direct correlation between yeast functional activity and binding data was established. Practical compounds with polar residues at C-4 of the pyrrolopyrimidine system required H-bond donor functionality for high potency.

MeSH terms

Binding, Competitive
Cell Line
Humans
Hydrogen Bonding
Purinergic P1 Receptor Antagonists*
Pyrimidines / chemistry
Pyrimidines / metabolism
Pyrimidines / pharmacology*
Radioligand Assay
Receptors, Purinergic P1 / genetics
Receptors, Purinergic P1 / metabolism
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Saccharomyces cerevisiae / genetics*

Substances

Purinergic P1 Receptor Antagonists
Pyrimidines
Receptors, Purinergic P1
Recombinant Proteins