Synthesis and SAR of thieno[3,2-b]pyridinyl urea derivatives as urotensin-II receptor antagonists.

The preparation and SAR profile of thieno[3,2- b ]pyridinyl urea derivatives as novel and potent urotensin-II receptor antagonists are described. An activity optimization study, probing the effects of substituents on thieno[3,2- b ]pyridinyl core and benzyl group of the piperidinyl moiety, led to the identification of p -fluorobenzyl substituted thieno[3,2- b ]pyridinyl urea 6n as a highly potent UT antagonist with an IC 50 value of 13 nM. Although 6n displays good metabolic stability and low hERG binding activity, it has an unacceptable oral bioavailability. [ABSTRACT FROM AUTHOR]