Serendipitous discovery of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine derivatives as novel HIV-1 replication inhibitors

Thienopyrimidine: A Promising Scaffold to Access Anti-Infective Agents

“…To summarize, all compounds showed better RNase H inhibition and lower integrase strand-transfer activity than raltegravir, the reference drug chosen by the authors. [3,2-d]pyrimidine derivatives able to inhibit the HIV-1 replication [20]. These compounds presented EC 50 values in the micromolar or submicromolar range.…”

Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2-d]pyrimidine and thienotriazolopyrimidine derivatives

“…On the other hand, some 2-substituted-thieno [3,2-d]pyrimidine--4-ones are considered to exert antihyperlipidemic (14) and anti-inflammatory activity (15). Also, 2-(phenylsulfonyl)methyl-thieno [3,2-d]pyrimidine derivatives act as novel HIV-1 replication inhibitors (16). Further, benzo-thieno [3,2-d]pyrimidin-4-one sulphonamide thio-derivatives act as inhibitors of COX-2, iNOS and ICAM-1 (17).…”

“…Compound 15 was obtained as yellow powder. [3,2-d]pyrimidin-4(3H)-one (16). -A mixture of 12 (0.01 mol) and an excess amount of hydrogen peroxide (5 mL) in acetic acid (30 mL) was heated gently under stirring for 10 h. The reaction mixture was allowed to cool to 0 °C.…”

“…On the other hand, compound 2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno [3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl--3-methyl-6-phenyl-thieno [3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl-thieno [3,2-d]pyrimidin-4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy-phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno [3,2-d]pyrimidin-2-yl)-sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize thieno [1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl--2-(methyl-sulfonyl)-6-phenyl-thieno [3,2-d]pyrimidin-4(3H)--one (16) through the reaction with the respective reagents. Moreover, the reaction of 16 with 4-phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno [3,2-d] pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N-{4-[(3-methyl-4-oxo-6-phenyl-3H,4H--thieno [3,2-d]pyrimidin-2-yl)-amino]phenyl}-methanesulfonamide (18).…”

8,18-Dithia-1,4,11,14-tetraazapentacyclo[11.7.0.03,11.05,9.015,19]icosa-3,5(9),6,13,15(19),16-hexaene-10,20-dione

“…O-, S-, and N-Methyl derivatives of 4H-3λ 2 -thieno [3,2-d]pyrimidin-4-one were intensively studied as novel HIV-1 replication inhibitors [1], Aurora kinase A inhibitors [2], inhibitors of the Salicylate Synthase (MbtI) from Mycobacterium tuberculosis [3], tankyrase inhibitors [4], and Cdc7 inhibitors for cancer therapy [5]. The convenient precursor for these compounds is 2-(chloromethyl)-4H-3λ 2 -thieno [3,2-d]pyrimidin-4-one (1), since the chlorine can be replaced by oxygen, sulfur, or nitrogen nucleophiles.…”