Af. Lewis et al., THIAZOLO[4,5-D]PYRIMIDINES .1. SYNTHESIS AND ANTI-HUMAN CYTOMEGALOVIRUS (HCMV) ACTIVITY IN-VITRO OF CERTAIN ALKYL DERIVATIVES, Journal of heterocyclic chemistry, 32(2), 1995, pp. 547-556
Alkyl derivatives of the thiazolo[4,5-d]pyrimidine congeners of guanin
e and uracil were prepared and assessed for in vitro activity against
human cytomegalovirus (HCMV). The finding that the 3-pentyl 1b and 3-h
exyl 1c derivatives of 5-aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dio
ne (1e) had potent in vitro anti-HCMV activity prompted a broader stud
y of alkyl derivatives in this ring system. A series of 3-alkyl deriva
tives of 1e, viz. 1f-w, were prepared by direct alkylation of the sodi
um salt of le and by subsequent modifications, 2a-d. For comparison wi
th 1c, ino-2-hexylaminothiazolo[4,5-d]pyrimidin-7(6H)-one (4) was prep
ared and studied. The 3-(2-alkenyl) derivatives of 1e were found to be
the more active antiviral agents with the Z isomer of en-1-yl)thiazol
o[4,5-d]pyrimidine-2,7(3H,6H)-dione (If) having the better therapeutic
index. Analogous 4-(2-alkenyl) derivatives of 2-aminothiazolo[4,5-d]p
yrimidine-5,7(4H,6H)-dione 6a and 6b were also prepared but were found
to have poor therapeutic indices. Single crystal X-ray diffraction an
alysis was used to unequivocally establish the structure of 1f.