Reyes-Arellano et al., Med Chem (Los Angeles) 2016, 6:9 DOI: 10.4172/2161-0444.1000400 t Short Review Article M e d i c i n a l c h e m i s t r y ISSN: 2161-0444 Medicinal chemistry Open Access Med Chem (Los Angeles), an open access journal ISSN: 2161-0444 Volume 6(9): 561-570(2016) - 561 Keywords: Azolines and imidazoles synthesis; Azolines and imidazoles in drug design; Nanoparticles from oxazolines Introduction Heterocycles are a very important functional group, especially in medicinal chemistry, because they constitute a common structural moiety in many drugs [1-4]. Azolines and imidazoles are key groups inside heterocycles, as they are not only a cornerstone of the synthesis pathway of these compounds, but also form part of potential [5] and marketed drugs [2]. Furthermore, in some cases azolines and imidazoles are the pharmacophore in drugs [6,7]. Consequently, azoline and imidazole synthesis has great importance in drug research. Te various interesting reviews of azolines and imidazoles [8-10] either focus on synthetic methods for obtaining these compounds or their biological activity, or both of these topics but with greater emphasis given to one of them [10]. In the current review, we focus on the synthesis of azolines and imidazoles that are directly involved in the preparation of drug precursors and the synthesis of potential drugs. We frst discuss azolines and then imidazoles. Azolines Azolines are fve-membered heterocycles with one double bond in the ring and two heteroatoms at positions 1 and 3, one of which is always nitrogen. Whereas imidazolines also contain nitrogen, oxazolines include oxygen, and thiazolines sulfur. Figure 1 shows some imidazolines, oxazolines and thiazolines that are either potential drugs or have important biological activity. *Corresponding author: Alicia Reyes-Arellano, National Polytechnic Institute, National School of Biological Sciences, Department of Organic Chemistry, Campus Santo Tomas, Carpio and Plan de Ayala S/N Colonia Santo Tomas, 11340 Mexico City, Mexico, Tel: +57296300; E-mail: areyesarellano@yahoo.com.mx Received September 03, 2016; Accepted September 15, 2016; Published September 20, 2016 Citation: Reyes-Arellano A, Gómez-García O, Torres-Jaramillo J (2016) Synthesis of Azolines and Imidazoles and their Use in Drug Design. Med Chem (Los Angeles) 6: 561-570. doi:10.4172/2161-0444.1000400 Copyright: © 2016 Reyes-Arellano A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Synthesis of Azolines and Imidazoles and their Use in Drug Design Alicia Reyes-Arellano*, Omar Gómez-García and Jenifer Torres-Jaramillo National Polytechnic Institute, National School of Biological Sciences, Department of Organic Chemistry, Mexico City, Mexico Abstract Heterocycles are very important functional groups, especially in medicinal chemistry. They are not only pivotal in the synthesis of drugs, but also form part of the structure of a diversity of drugs, vitamins, natural products and biomolecules. The importance of azolines and imidazoles in heterocycles lies in the fact that their derivatives are known for analgesic, antifungal, antihypertensive, antiobesity, anticancer, and other biological activity. Additionally, they can inhibit butyrylcholinesterase, acetylcholinesterase, carboxylesterase and quorum sensing. Due to these properties, the present contribution reviews the use of azoline and imidazole moieties in recent drug synthesis based on classic as well as non-classic methods, the latter employing microwave and sonication energies. Also included is the preparation from oxazoline of nanostructured material having biomedical applications. Hence, the present focus is on the synthesis of azolines and imidazoles that are directly involved in the preparation of drug precursors and potential drugs. Compound 1 acts as a COX-2 inhibitor precursor [11], compound 2, methoxy-idazoxan / RX821002 (α2), as an α-adrenergic antagonist [1], compounds 3 and 7 as quorum sensing inhibitors [12,13], compound 4, epi-oxazoline halipeptine D, as a potent anti-infammatory agent [14], compound 5, (-)-spongotine A, as an antitumor agent with moderate cytotoxicity against human leukemia K-562 [15,16], and compound 6, brasilibactin A, as a cytotoxic siderophore [17]. Synthesis and pharmacological activity of azolines Te synthetic routes for building azolines can be divided into classic methods that use conventional energy, and non-classic methods accomplished with microwave (MW) or ultrasound energy. Classical methods of synthesis: One commonly used method for the synthesis of azolines starts from an aldehyde and a source of heteroatoms, usually an ethylenediamine for imidazolines, an ethanolamine for oxazolines, and a cysteamine for thiazolines. Afer obtaining azolidines in this way, oxidants (e.g., I 2 , tert- buthyl hypochlorite (t-BuOCl), N-chlorosuccinimide (NCS), N- bromosuccinimide (NBS) and N-iodosuccinimide (NIS) are utilized to achieve azolines. For instance, NCS and t-BuOCl have been applied to the total synthesis of (-)-spongotine A, 5 [15]. In other reactions, oxidation with NCS gave an 88% yield, but spongotine was obtained at 52% yield (Scheme 1). Scheme 1: Total synthesis of (-)-spongotine A, which displays moderate cytotoxicity against human leukemia K-562. 1 2 3 4 5 7 6 Figure 1: Examples of biologically active azolines, including blue imidazolines, pink oxazolines, and red thiazolines.