Table 8. In Vitro Mouse Liver Microsome (MLM) Stability, in Vivo PK Properties, and Caco-2 Permeability of AMTz Inhibitors.

						Caco-2 Pappe,f (10–6 cm/s)
compd	MLM stability (%)a	Cmax(PO) (μM)c	AUC(PO) (μM·h)d	t1/2(PO) (h)	F (%)e	A → B	B → A
6	89	6.35	4.20	0.8	nd	nd	nd
21e	90	9.75	4.48	2.0	nd	nd	nd
7e	70	10.16	9.97	0.6	nd	nd	nd
3a
(i) mouse	(i) 64	(i) 16.83	(i) 14.89	(i) 0.45	(i) 45	8.5	35
(ii) rat	(ii) 35b	(ii) 0.34	(ii) 0.22	(ii) 0.5	(ii) 0.2
21b
(i) mouse	(i) 76	(i) 26.71	(i) 18.5	(i) 1.12	(i) 98	31	29
(ii) rat	(ii) 82b	(ii) 6.5	(ii) 18.5	(ii) 1.3	(ii) 68
22d	97	27.22	20.98	1.0	68	23	51
7a	100	32.03	21.61	0.89	nd	23	33

^aMouse liver microsome (MLM) stability values represent the percentage of compound remaining after 30 min.

^bRat liver microsome (RLM) stability values represent the percentage of compound remaining after 30 min. Mouse plasma PK parameters were determined following a single po dose at 50 mg/kg or iv dose at 10 mg/kg. Rat plasma PK parameters were determined following a single po dose at 20 mg/kg or iv dose at 4 mg/kg.

^cC_max: maximum concentration.

^dAUC: area under curve.

^end: not determined.

^fP_app: permeability coefficient.