Synthesis of 3-aryl-1,2,4-benzotriazines via intramolecular cyclization of solid-supported o -hydrazidoanilines
- PDF / 498,113 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 89 Downloads / 160 Views
SHORT COMMUNICATION
Synthesis of 3-aryl-1,2,4-benzotriazines via intramolecular cyclization of solid-supported o-hydrazidoanilines Edwar Cortés · Luciana Méndez · Ernesto G. Mata · Rodrigo Abonia · Jairo Quiroga · Braulio Insuasty
Received: 7 May 2012 / Accepted: 24 September 2012 / Published online: 10 October 2012 © Springer Science+Business Media Dordrecht 2012
Abstract An efficient solid-phase protocol for the rapid generation of libraries of biologically promising 1,2,4-benzotriazines, including amino acid-derived components, is described. Keywords Solid-phase organic synthesis · Aromatic nucleophilic substitution (SN Ar) · Hydrazidoanilines · 1,2,4-Benzotriazines
Introduction The synthesis and reactivity of 1,2,4-triazines and related compounds have been widely studied. This family of heterocycles exhibits promising biological activities, such as anticancer, antinociceptive, antibacterial and fungicidal properties [1–7]. For instance, compound 1 is a potent, ligand efficient, selective, and orally efficacious antagonist of the adenosine A2A receptor [8] (Fig. 1). The 1,2,4-benzotriazines, in particular, constitute an important group of heterocyclic compounds due to the broad biological activity spectrum displayed by them [9,10]. For example, tirapazamine 2 is a promising antitumor agent that Electronic supplementary material The online version of this article (doi:10.1007/s11030-012-9400-3) contains supplementary material, which is available to authorized users. E. Cortés · R. Abonia · J. Quiroga · B. Insuasty Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, Cali A.A. 25360 Colombia L. Méndez · E. G. Mata (B) Instituto de Química Rosario (IQUIR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario-CONICET, Suipacha 531, S2002LRK Rosario, Argentina e-mail: [email protected]
selectively causes DNA damage in hypoxic tumor cells [11], while their analogs 3 (a: R1 = Cl, R2 = cyclohexyl; b R1 = Cl, R2 = Ph) have even more potent cytotoxic activity and hypoxic selectivity than tirapazamine [12]. On the other hand, the spirobenzotriazine 4 displays high selectivity as a ligand for the σ1 receptor subtype in CNS and peripheral tissues [13], and fluorinated compound 5 has been tested for antiviral and cytotoxic activity on Vero cell cultures showing activity against severe diseases caused by smallpox and some other pathogenic viruses [14]. In addition, antimicrobial [15], herbicidal [16], antimalarial [17], human blood rheology regulant [18], antifungal [19], and antiinflammatory [20] activities have also been reported for these kind of compounds. Combinatorial chemistry-related techniques have been widely applied to the discovery of novel lead molecules and the optimization of compound libraries [21,22]. Particularly, solid-phase organic synthesis (SPOS) has experienced a spectacular growth, since the arrival of the small-molecule combinatorial chemistry to the field of drug discovery [23–26]. For library production, SPOS simp
Data Loading...
