In comparison with the lead JH122, receptor binding affinities of the test compounds 1a-f have been determined by radioligand displacement studies, as described previously , applying membranes of HEK 293T cells transiently expressing the human OX1R or OX2R (Table ). The results confirm that the substitution of chloride in JH112 by fluoride (1e) only marginally decreased OX1R affinity by a factor of 1.6. All derivatives lacking the (S,S)sec-butyl substituent at the diazepane ring (1a-d) showed one-digit nanomolar affinities for both OXR subtypes in the range from 0.8 nM (Ki(OX2R), 1d) to 2.5 nM (Ki(OX1R),