Table 1. SAR Study of TRH Mimetics on Physicochemical Properties, CNS Effects, and Rat TRH Receptor Binding Affinities.

^aclog P was calculated using ChemBioDraw Ultra.

^bSlog P was calculated using MOE.

^cEffective dose for increasing rectal body temperature by 1 °C per h (nmol/°C/kg body weight) in reserpine-induced hypothermia mice. Each value represents the mean ± SD of at least three animals. The formula for computation is as follows: AUC_0–7h: area under the rectal temperature–time curve for 7 h, Administration dose (5 or 50 μmol/kg)/((AUC_0–7h of test compounds – temperature at time 0 × 7 h of test compounds) – (AUC_0–7h of saline temperature at time 0 × 7 h of saline)/7 h).

^dK_i values were obtained from the inhibition to [³H]-(3-Me-His²)-TRH using a membrane preparation of the rat whole brain.

^eNo data.

^fNot assayed.