Synthesis of Pyrimidine, Thiazolopyrimidine, Pyrimidotriazine and Triazolopyrimidine Derivatives and their Biological Evaluation

Abstract

Pyrimidin-4-one-2-thione (3) was synthesized via the reaction of thiourea (1) with ethyl benzoylacetate (2) and was taken as a starting material for the present study via its reactions with the halogen-containing reagents 6a-d and lOa-c to give the corresponding thiazolopyri midines 8, 9 and 12a-c. The 2-hydrazino derivatives 5 were synthesized either via the reaction of 3 or 4 with hydrazine hydrate. Compound 5 reacted with 6a-c and lOa-c to give the corre sponding pyrimidotriazines 17a-c and 19 respectively. A lso, compound 5 reacted with the active methylene-containing reagents 13 and 2a,b to give the corresponding 2-pyrazolopyrimidines 15 and 22a,b respectively. On the other hand, the triazolopyrimidines 21a,b and 30a,b were also obtained via the reaction of 5 with each of formic acid, acetic anhydride, ethyl chloroformate and carbon disulfide respectively. Some o f the newly synthesized heterocyclic derivatives were tested for their biological activity.

The identification of GPR3 inverse agonist AF64394; The first small molecule inhibitor of GPR3 receptor function

“…) is condensed with formic acid to afford, after chlorination with POCl 3 , the 5-Chloro-[1,2,4]triazolo[4,3-a]pyrimidine(7) 13,14. Simple chloride displacement then affords the final compounds (8) (Scheme 3).…”

Reactivity of (2‐methylsulfanyl‐4‐oxo‐6‐phenyl‐4h‐pyrimidin‐3‐yl)‐acetic acid methyl ester towards hydrazine hydrate and benzylamine

“…2-Methylsulfanyl-6-phenyl-3H-pyrimidin-4-one and 2-mercapto-6-phenyl-3H-pyrimidin-4-one were synthesized as reported in references [20,25].…”

“…6-Phenyl-2-thiouracil unlike its 6-methyl analogue is not yet studied sufficiently. Few recent publications, however, show 2-mercapto-6-phenyl-3H-pyrimidin-4-one derivatives to exhibit pharmacological properties, such as, anti-HIV-1 [16], antibacterial or antifungal [20] activity. Consequently it was expedient from this point of view to use 2-mercapto-6-phenyl-3Hpyrimidin-4-one as a starting material.…”

Novel Pyrimidinone Derivatives: Synthesis, Antitumor and Antimicrobial Evaluation

“…22) Alternatively, another approach was achieved by alkylation of compound 4a, followed by treatment of the formed S-alkylated products with hydrazine hydrate to afford a 30% yield of 7a according to reported method. 23) The IR spectra of 7a, c showed two absorption bands at 3320 and 3282 cm H-NMR spectra showed the two characteristic singlets of NH 2 around 7.07 and 7.57 ppm respectively, exchangeable with D 2 O (cf.…”