A 1H nmr study of the amide-bond conformational equilibrium in pirenzepine

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Abstract
The hindered rotation about the exocyclic amide bond of pirenzepine has been studied using 1H nuclear magnetic resonance spectroscopy. The ratios of the two slowly interconverting conformations (1:1·76 at 2 °C and 1:2·37 at 30 °C) and the rate of interconversion (1 ± 0·5 s−1 at 20 °C and 247 ± 20 s−1 at 80 °C with ΔG80 = 71 KJ mol−1) have been measured at various temperatures. The observed rapid rates of interconversion allow us to eliminate the rate of conformational selection of forms II and III as a major contributor to the slow phase of the binding kinetics observed when pirenzepine binds to muscarinic receptors from rat brain (Stockton, Birdsall, Hulme and Burgen, unpublished results).