Gerald S. Ponticello

Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted-amino)-2-hydroxypropoxy]phenyl]imidazole class.

A series of 2-[4-[3-(substituted-amino)-2-hydroxypropoxy]phenyl]imidazoles is described. The compounds were investigated in vitro for beta-adrenoceptor antagonism, and several examples were found to be selective for the beta 1-adrenoceptor. The structure--activity relationship exhibited by this series of compounds is discussed. (S)-2-[p-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-2-hydroxypropoxy]phenyl]-4-(2 -thienyl)imidazole [(S)-13] was over 100 times more selective than atenolol for the beta 1-adrenergic receptor and has been selected for in-depth studies.

The synthesis of dihydrothieno[2,3-b]thiophenes by a metal-halogen exchange initiated intramolecular acylation

Abstract An intramolecular acylation of 3-bromothiophenes initiated by a lithium-bromine exchange reaction is presented as a route to the title compounds.

Dorzolamide, a 40-Year Wait

Dorzolamide, on the basis of its pharmacological profile and lack of undesirable side effects in safety assessment studies together with the fact that it could be formulated in solution at 2%, underwent extensive clinical studies.