Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles

Abstract

A set of new pyrimido [5,4-b]indole derivatives that are structurally related to some non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1 IIIB cells. Preliminary structure -activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy.

Chalcones as Versatile Synthons for the Synthesis of 5- and 6-membered Nitrogen Heterocycles

“…The indole nucleus possesses a wide range of biological activities being a biologically accepted pharmacophore in medicinal compounds. Antiinflammatory [70], antifungal [71], antimicrobial [72], anticancer [73,74], anti-HIV [75], antioxidant [76], and antiviral [77] activities, among many others, are some examples of the biological potential of indole derivatives. There was only one report concerning the synthesis of indoletype compounds using chalcones as starting materials.…”

Biological importance of the indole nucleus in recent years: A comprehensive review

“…for their possible HIV inhibitory activity. The derivative ( 28 ) formed by substitution at position 2 in analog‐I and derivative ( 29 ) at position 2, 4 in analog II (formed in 65% and 64% maximum yield) were reported to be the inhibitors of wild and mutant HIV‐1 RT types in an “ in vitro ” recombinant HIV‐1 RT screening assay as well as anti‐infectives in HLT4lacZ‐1 IIIB cells [15]. …”

Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts

“…A five-membered pyrrole ring and benzene are fused to form indole [1]. Indoles are important heterocyclic compounds because they are an integral part of many alkaloids and biologically active compounds [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Thus, having enormous activities, indole has always acquired the attention of researchers.…”

“…They synthesized 2-substituted indoles having a nitro or an amino substituent selectively on the C-5, C-6, or C-7 position. The desired product formation was accomplished by utilizing different solvents; with DMA, NO 2 -indole derivatives (15) were obtained effectively, whereas choosing DMF resulted in NH 2 -indole derivatives (16) selectively (Scheme 7). When DMF was used as a solvent in situ, a derivative of ammonium formate was produced, which acted as a hydrogen source in the presence of palladium salt [138].…”