Table 5.

Antiviral activity of alkoxyalkyl esters of various types of acyclic nucleoside phosphonates

Compound	EC₅₀, μM
HPMP nucleosides	Vaccinia	HCMV	HIV-1

(S)-HPMPA	2.7^a	0.82^a	77.5^b
HDP-(S)-HPMPA	0.01	0.003	0.007
(S)-HPMPC (Cidofovir, CDV)	46.2^c	0.38^d	-
HDP-CDV (CMX001)	0.8	0.009	-
cHPMP-5-aza-C	2.12 e	0.070 ^e	-
HDE-cHPMP-5-aza-C	0.037	0.00038	>0.80
PME nucleosides	Vaccinia	HCMV	HIV-1

PMEA (Adefovir)	-	-	1.1^f
HDP-PMEA	-	-	0.000015
PMEDAP	>10^g	13^g	0.08^f
HDP-PMEDAP	0.6	0.5	0.000016
PME-N⁶-cyPr-DAP	4.0^g	0.4^g	0.07^f
HDP-PME- N⁶-cyPr-DAP	0.10	0.02	<0.00001
PPen nucleosides	HIV-1	HBV (2.2.15)	HBV (AD38)

PPen A,C,G,T	>100^h	>100^h	>30^h
HDP-PPen-A	>30	15.7	1.5
HDP-PPen-C	>20	2.9	3.9
HDP-PPen-G	7.5	1.8	2.4
HDP-PPen-T	>20	0.66	2.0
PMP nucleosides	HIV-1	HBV (2.2.15)	HBV (AD38)

PMPA (Tenofovir)	3.20ⁱ	7.2ⁱ	2.25ⁱ
HDP-PMPA (CMX157)	0.012	1.6	0.49
PPM nucleosides		HCMV
PPMG (ACV methylene phosphonate)		5.4^j
HDP-PPMG		0.24
PPMDAP		>100^j
HDP-PPMDAP		2.85
PPM-N⁶-cyPr-DAP		>90^j
HDP-PPM- N⁶-cyPr-DAP		1.6
HPPMP nucleoside	Vaccinia	HCMV	HSV-1

HPMPC (CDV)	31	1.2	3.3
HDP-P-HPMPC	3.2^k	0.26^k	0.06^k

References:

Beadle et al, 2006;

Hostetler et al, 2006;

Kern et al, 2002;

Beadle et al, 2002;

Krečmerová et al, 2007;

Valiaeva et al, 2006;

Prichard et al, 2008;

Choo et al, 2007b;

ⁱ

Painter et al, 2007;

Ruiz et al, 2005;

Ruiz et al, 2006.

Abbreviations: HPMPA, 9-(S)-(3-hydroxy-2-phosphonomethoxy-propyl)adenine; PMEA, 9-(2-phosphonomethoxyethyl)adenine; PMEDAP, 9-2-(phosphonomethoxyethyl)-2,6-diaminopurine; PME-N⁶-cyPr-DAP, 9-(2-phosphonomethoxyethyl) -2-amino-6-cyclopropylaminopurine; PPen-A, 9-(5-phosphono-pent-2-en-1-yl)adenine; PMPA, 9-(R)-(2-phosphonomethoxypropyl)adenine; PPMG, 9-(phosphonopropoxymethyl)-guanine; HDP-P-HPMPC, hexadecyloxypropyl-phospho-cidofovir; HDP, hexadecyloxypropyl; HDE, hexadecyloxyethyl.