20-F-20-C-Methyl Nucleosides and Nucleotides for the Treatment of Hepatitis C Virus: from Discovery to the Clinic - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 249

Table 11.2 Comparison of PSI-6130 to prodrug RG7128

NH 2

O

N

N

O

O

O

O O

F

20
(RG7128)

Stability SGF a
(pH1.2, 37 1C)
t 1/2 (h)

Stability SIF a
(pH7.4, 37 1C)
t 1/2 (h)

Rat PK 10mg kg 1
AUC 0 24 (mghmL 1 )
C max (mgmL 1 )

EC 90 (mM)
Clone A

Caco2 Papp
( 10 6 cm s 1 ) Compound CC 50 (mM)

PSI-6130 3.03 4100 420 420 0.21 AUC (parent) ¼ 2.97

C max ¼ 0.6

RG7128 2.5 4100 25 36 6.4 AUC (parent) ¼ 16.17

C max ¼ 1.86

a SGF ¼ simulated gastric fluid; SIF ¼ simulated intestinal fluid.