ABSTRACT
Potassium channel activators (KCAs) represent a varied structural class of molecules that interact with ATP-sensitive potassium channels (KATP). Their action on these ion channels results in smooth muscle relaxation and has led to KCAs being proposed as potential drugs for the treatment of asthma and hypertension, for example. A study of the conformations adopted by this class is of interest in the design of novel therapeutic agents and in the characterization of the KATP channel itself. This chapter therefore includes conformational analysis data on the three main classes of KCA - namely, cromakalim (CRK), aprikalim, pinacidil and some of their analogues. The majority of the calculations reported in this chapter are at the semi-empirical MNDO level of theory, using the AMI Hamiltonian. This seems to have been accepted as the de facto standard in this field, notwithstanding its limitations, such as low barrier heights and poor description of some sp 2 nitrogens. Novel calculations made for this chapter have used this theoretical method for consistency with previously published work.
