Chapter I. Synthesis, modification and bioactivity of bicyclic thieno[3,2-D]pyrimidines

1.1.19There are some reactions that produce of tienopyrimidini derivatives
The new derivatives were tested for their inhibitory potencies against the catalytic domain of PDE7A1 and full-length PDE4D2 as described in the Experimental Section. Among the new heterocyclic compounds, some of them are more potent than the previous quinazoline derivatives 2–5. [29] In addition, compounds 15, 19, 23, 25, 29, and 39, also inhibit PDE4, and therefore can be considered as potential PDE7/PDE4 dual inhibitors for the treatment of T-cell disorders. In addition, the Smethyl derivatives have better activity than the previously described compounds (IC50 values of 0.51 mm for 15 and 0.13 mm for 23. Strikingly, among the members of this S-methyl family, compounds 18 and 22, which bear a phenyl group at position 3, are less active than 15, 19, 23, and 25, which are mono- or di-substituted at the ortho position of the benzene ring. The compounds with the benzene fused ring replaced by a thieno or benzothieno moiety show similar activity.
The-(11R,20 S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A2A receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A2A receptor. These derivatives show selectivity against the A1 receptor. Furthermore, some of these compounds have been shown to have in vivo activity in a commonly used model, suggesting the potential for the treatment of Parkinson’s disease[63-65].
1.1.19.1 The synthiesis and modification of tiopyrimidine derivatives
There are some substance that to alter some structure to other which is helped us to understand how to structure it. We describe herein the discovery and development of a series of 4-arylthieno[3,2-d]pyrimidines which are potent adenosine A2Areceptor antagonists. These novel compounds show high degrees of selectivity against the human A1,A2Band A3 receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson’s disease.

Reagents and conditions: (a) POCl3, reflux, 2 h, 35%; (b) PhCHO, N,N-dimethylimidazolium iodide, NaH, THF, reflux, 15 min, 21%; (c) NaBH4, MeOH, rt, 1 h, 27%.