Table 5. Selected SARs from Substituted Phenyl P1 Groups^a.

compd	R1	R2	R3	R4	PKa IC50 (nM)	Caco-2 Papp (×10–6 cm/s)	HLM CLint (μL/min/mg protein)	kinetic sol 0.1 N HCl (mg/mL)	kinetic sol aq assay buffer (pH 7.4) (mg/mL)	cLogPb	LLE
13a	H	F	OCH3	F	3.0	3.2	36	n.d.	n.d.	2.4	6.1
13b	CH2OCH3	F	OCH3	F	6.0	18	92	>0.12	>0.12	2.8	5.4
13c	CH2N(CH3)2	F	OCH3	F	6.3	14	280	n.d.	n.d.	2.4	5.8
13d	CH2OCH3	F	OCH3	H	17	25	45	>0.12	>0.12	2.6	5.2
13e	N(CH3)2	F	OCH3	H	73	23	120	>0.12	>0.12	2.7	4.4
13f	cyclopropyl	F	OCH3	H	23	24	170	>0.11	0.058–0.11	3.2	4.4
13g	CH2OCH3	F	OH	H	440	n.d.	n.d.	>0.12	>0.12	2.2	4.2
13h	CH2OCH3	F	CH2CH3	H	140	n.d.	n.d.	0.029–0.059	>0.12	3.2	3.7
13i	CH2OCH3	F	OCHF2	H	150	n.d.	n.d.	0.063–0.12	>0.12	2.6	4.2
13j	CH2OCH3	F	OCH3	Cl	5.5	9.3	120	>0.12	>0.12	3.4	4.9
13k	CH2OCH3	F	OCH3	CN	1.0	14	58	>0.12	>0.12	2.1	6.9
13l	CH2OCH3	H	OCH3	F	35	n.d.	n.d.	>0.12	>0.12	2.4	5.1
13m	CH2OCH3	CHF2	OCH3	F	6.8	11	100	>0.13	>0.13	3.1	5.1

^an.d., not determined.

^bcLogP values generated using ACD/Laboratories Percepta software.