Fig. 2. Correlation between the experimentally determined ligand (2–6 and 53–75) pKi values and calculated van der Waals volumes of the respective carbamoyl residues. Two types of outliers (squares) were observed: (1) argininamide 1, devoid of a carbamoyl substituent, supposed to bind in the same orientation as 2, but unable to occupy the subpocket between TM V and VI (cf.Fig. 1); (2) compounds 7, 9, 76 and 78, bearing bulkier carbamoyl moieties than 72, considered to bind to the Y1R in a totally different orientation compared to 2.
