Table 1.

Binding inhibition and lipophilicities of V_1a ligands 1, 6b-c, 8a-l.

Compounds	R	R1	R2	logD7,4	% Binding inhibition a (concentration)
					(10−9M)	(10−8M)
(1S,5R)-1		OCH3	H	4.7	51.4	87.9b
(1R,5S)-1		OCH3	H	4.7	7.1	8.9b
6b		H	H	4.8	33.4	77.1
6c		OCH2CH2F	H	4.9	45.1	92.6
8a		OCH3	H	3.9	2.9	33.9
8b		OCH3	H	4.0	9.7	16
8c		OCH3	H	6.0	1.8	18.7
8d		OCH3	H	2.9	4.4	28.7
8e		OCH3	H	3.5	−4.7	44.2
8f		OCH3	H	2.8	5.2	39.5
8g		H	H	5.0	23.7c	84.3
8h		H	H	4.4	10.5	28.9
8i		H	H	4.4	12.8	43.9
8j		H	H	4.4	−6.6	18.2
8k		H	F	5.8	22.8	81.2
8l		H	F	4.5	2.4	19.8

^aValues are the means of two experiments, each in duplicate.

^bThe V_1a inhibition binding affinity constant values of (1S,5R)-1 (K_i = 0.66 nM) and (1R,5S)-1 (K_i > 10 nM) were determined in a separate binding assay. This result is in agreement with previously published data for (1S,5R)-1 (K_i = 0.1 nM) [22].

^cCompound 8g was described previously (K_i = 0.05 nM) [22].