Phenols are unique among aromatic substituents in their potential hydrogen bonding interactions with proteins since the oxygen atom can function as both a proton donor and acceptor. The acidity of the phenol in the aqueous environment is a key determinant of its ability to transfer or accept a proton from the receptor protein. To probe the potential role of phenol acidity in influencing the binding mode of the thieno [2,3-d]pyrimidines two parallel series of analogs were synthesized in the para-phenol (4-8) and meta-phenol (9-13) series (Scheme 1).