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. 2024 Oct 16;67(20):18204–18220. doi: 10.1021/acs.jmedchem.4c01510

Table 1. In Vitro HIV (MJ4) Activity and HLM Stability Profiles of HTP-Derived TFV Prodrugs with Varied Sulfur Position and Chain Length.

compound lipid motif linear atom # HLM t1/2 (min)a [% remaining]b HIV (MJ4) IC50 (μM)a CC50 (μM)a therapeutic indexc
TXL C3H6–O-C16H33 20 41.6 ± 9.0d 0.018 ± 0.010d 97.6 ± 2.7 5420
2a C3H6–S-C16H33 20 41.7 ± 2.3 0.010 ± 0.002d 49.8 ± 2.9 4980
2b C2H4–S-C17H35 20 66.1 ± 2.6 0.004 ± 0.003 28.6 ± 3.7 7150
2c C6H12–S-C13H27 20 66.2 ± 3.0 0.073 ± 0.011 >100 >1370
2d C9H18–S-C10H21 20 13.3 ± 0.5 0.058 ± 0.009 >100 >1720
2e C12H24–S-C7H15 20 20.6 ± 0.1 0.338 ± 0.004 >100 >296
2f C15H6–S-C4H9 20 19.7 ± 0.003 0.302 ± 0.062 >100 >331
2g C3H6–S-C12H25 16 11.3 ± 0.2 0.583 ± 0.188 >100 >532
2h C3H6–S-C14H29 18 15.6 ± 0.1 0.007 ± 0.006 >100 >16,700
2i C3H6–S-C18H37 22 >120 [>95%] n.d. n.d. n.d.
2j C3H6–S-C20H41 24 >120 [>95%] n.d. n.d. n.d.
a

n = 2.

b

Relative percent remaining of prodrug at 120 min. Linear atom # does not count H or F.

c

Therapeutic index = CC50/HIV (MJ4) IC50.

d

n = 4.