Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors

Table 1

Molecular structures and PDE2 inhibitory activity of purin-6-one derivatives (see Scheme 1, compounds 2a–2q).

Compound	R	R^1	% Inhibition (at 10 M inhibitor)
2a	–CH2CH2OH	3-Methoxybenzyl	48
2b	–CH2CH2OH	3,4-Dimethoxybenzyl	78
2c	–CH2C6H5	2-Methylbenzyl	35
2d	–(CH2)3C6H5	3,4-Dimethoxyphenyl	44
2e	–(CH2)3C6H5	Benzyl	78
2f	–(CH2)3C6H5	2-Methylbenzyl	35
2g	–(CH2)3C6H5	4-Chlorophenyl	18
2h	–(CH2)3C6H5	2,4-Dichlorophenoxyethyl	42
2i	–(CH2)4C6H5	Benzyl	78
2j	–(CH2)4C6H5	3-Methoxybenzyl	95 (1731)
2k	–(CH2)4C6H5	2-Methylbenzyl	24
2l	–(CH2)4C6H5	2,4-Dichlorophenoxyethyl	34
2m	–(CH2)4C6H5	4-Chlorophenyl	30
2n	–(CH3CHOH)CHCH2C6H5	Benzyl	73
2o	–(CH3CHOH)CHCH2C6H5	2-Methylbenzyl	70
2p	–(CH3CHOH)CH(CH2)3C6H5	Benzyl	100 (184)
2q	–(CH3CHOH)CH(CH2)3C6H5	4-Chlorophenyl	99 (3427)
2r	–(CH3CO)CHCH2C6H5	Benzyl	75
2s	–(CH3CO)CHCH2C6H5	2-Methylbenzyl	78
2c-1	1-Allyl-9-benzyl-2-(2-methyl-benzyl)-1,9-dihydro-purin-6-one		56
2c-2	6-Allyloxy-9-benzyl-2-(2-methyl-benzyl)-9H-purine		9

IC₅₀ (nM).