Synthesis of aminopyrimidylindoles structurally related to meridianins

Abstract

The synthesis of new meridianin derivatives substituted at the C-5′ position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. The 2-aminopyrimidine ring was obtained via a Bredereck synthesis. Aryl groups were introduced by Suzuki cross-coupling after bromination of the 2-aminopyrimidine ring at the C-5′ positio

Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co–crystal structure

“…3B) with CLK1-ATP binding site. PDB codes:5J1V (13) and 5J1W (14). The hydrogen bonds are shown by dashed lines.…”

Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization

“…Next, 1 H -benzo[ d ][1,2,3]triazol-1-yl-(1-methyl-1 H -indol-3-yl)methanone ( 4a ) was converted into its α-nitroketone 5a by treating with nitromethane in the presence of potassium tert -butoxide in DMSO [62]. 1-(1-Methyl-1 H -indol-3-yl)-2-nitroethanone ( 5a ) was reacted with N , N -dimethylformamide dimethyl acetal to form ( E )-3-(dimethylamino)-1-(1-methyl-1 H -indol-3-yl)-2-nitroprop-2-en-1-one ( 6a ) [63–66], which was then converted to 4-(1-methyl-1 H -indol-3-yl)-5-nitropyrimidin-2-amine ( 7a ) in the presence of guanidine hydrochloride. Finally, the desired substrate 4-(1-methyl-1 H -indol-3-yl)pyrimidin-2,5-diamine ( 2a ) was obtained by reducing 7a with H 2 /Pd in methanol.…”

Introducing "Synthesis Route-Based Hit Identification Approach" as a Tool in Medicinal Chemistry and Its Application in Investigating the Antiproliferative and Antimicrobial Effects of 2- Aminopyrimidine Derivatives

“…Methylketones (1a-h) were allowed to react with dimethylforamide-dimethylacetate (DMF-DMA) to produce 3-(dimethylamino)-1-aryl-2-en-1-ones (2a-h) [18]. The key intermediates could be further condensed with guanidine hydrochloride to form the corresponding aminopyrimidine ring system (3a-h) [18] Structure confirmation of the synthesized intermediates and the final products was performed using IR, NMR, and Mass spectrometry.…”

“…Representative procedure for the preparation of (2a-h) [18] To a solution of acetophenone (84 mmol) in DMF (16ml), was added DMF-DMA (84 mmol) and the solution was heated under reflux for 24 h. Brine (25 ml) was added to the reaction mixture after cooling and the mixture was International Journal of Drug Discovery ISSN: 0975-4423 & E-ISSN: 0975-914X, Vol. 3, Issue 2, 2011 then extracted with CH2Cl2 (3×25 ml).…”