Identification and SAR of a new series of thieno[3,2-d]pyrimidines as Tpl2 kinase inhibitors

Synthesis of thiophene and N-substituted thieno[3,2-d] pyrimidine derivatives as potent antitumor and antibacterial agents

“…Compounds 19a and 19c exhibited moderate to good antitumor activity due to the electronic nature of the substituent on the phenyl ring att ached to [1,3,4] ; activity of these compounds is probably due to the presence of a substituent in the phenyl ring att ached to thieno[3,2-d]pyrimidine such as (N-carbamimidoyl and N-pyrimidinyl) benzenesulfonamide in 5a,b, [1,2,4]triazolopyrimidine att ached to p-fl uorophenyl in 6b and thioxotriazole moiety fused with the pyrimidine ring in 11. Furthermore, compounds 4a, 5c, 6a,c, 9, 10, 14, 17 and 18 exhibited moderate to low antitumor activity on the three tumor cell lines, while compounds 4c and 12 exhibited very low antitumor activity.…”

“…They have been widely employed due to their activities as antitumor (3,4), antimetabolite (5), antiviral, anti-HIV-1 (6), antiproliferative (7), antimicrobial (10,11), analgesic and anti-infl ammatory (12,13) agents, as well as kinase (8) and phospho-diesterase IV inhibitors (9). Among these active compounds, thieno [3,2-d]pyrimidines have generated wide-spread interest due to their remarkable antitumor activities (3,4,14). Thus, substituted thieno [3,2-d]pyrimidines exert pronounced activity as PI3K inhibitors (GDC-0941) and EGFR and VEGFR dual inhibitors, which are used in the treatment of cancers (15)(16)(17).…”

Synthesis and antimicrobial activity of some new thienopyrimidine derivatives

“…Compound 13 (0.5 g, 1.2 mmol) was heated under reflux for 3 h with triethyl orthoformate (5 ml) in the presence of a few drops of glacial acetic acid. The precipitate that formed after cooling was collected and recrystallized from an ethanol-water mixture (2:1) to give 14 as pale yellow crystals, 75 % yield; mp >300 -10-(p-tolylamino)-3,4-dihydro-2H-pyrimido[5',4':4,5]thieno[2,3-e]pyrimido[1,2-c][1,2,3]triazine (15). To a suspension of compound 13 (0.46 g, 1.11 mmol) in a mixture of acetic acid (10 ml) and hydrochloric acid (2 ml), in an ice bath a solution of sodium nitrite (0.31 g, 4.7 mmol) in 5 ml H 2 O was added during 5 minutes.…”

“…To a suspension of compound 13 (0.46 g, 1.11 mmol) in a mixture of acetic acid (10 ml) and hydrochloric acid (2 ml), in an ice bath a solution of sodium nitrite (0.31 g, 4.7 mmol) in 5 ml H 2 O was added during 5 minutes. After addition, the ice bath was removed and stirring was continued for 5 h. the mixture was diluted with water and the solid product obtained was collected and recrystallized from dioxane to afford 15 (17). A mixture of compound 13 (0.83 g, 2 mmole), and chloroacetyl chloride (0.4 ml, 3 mmole) in dioxane ( 20 ml) was heated on a water bath for 2h.…”

“…Pyrimidine and thienopyrimidine derivatives display a broad variety of biological activities, such as anticancer, [1][2][3][4][5][6] antiviral, [7][8][9] antitumor, [10][11][12][13][14][15] anti-inflammatory, 16,17 antimicrobial, [18][19] antimalarial 20 and antioxidant activities. 21,22 Also thienopyrimidines have long been the subject of chemical and biological research.…”