Drug discovery heterocycles

N-Heterocycles as neuronal acetylcholine receptors in drug discovery 97JMC4169. 

Several review articles have appeared covering the synthesis of heterocycles on insoluble supports for the production of compound libraries for drug discovery [1-4]. In this chapter, these syntheses have been organized according to the type of heterocycle prepared. 

Cyclative cleavage to five- and six-membered ring heterocycles is dominated by the synthesis of hydantoins and diketopiperazines, respectively. In the seven-membered ring case, it is the benzodiazepine nucleus that has attracted attention, due to its status as a privileged structure in drug discovery. In the precombinatorial days, Camps et al,33 reported a... 

Based on a new substantial body of pharmacological and clinical evidence, it is anticipated that the modulation of the effects of corticotropin releasing hormone or factor (CRH or CRF) may eventually play a role in the treatment of depression or anxiety-related disorders. This interest in CRH as a new important target for drug discovery is clearly evident. Recently Gilligan et al. [74] have observed that the Suzuki reaction can be used to synthesize a variety of aryl-substituted heterocyclic antagonists of the CRH receptor (Eq. (43)). 

He has served as the director of the Istituto Farmacochimico (March 1995-June 1999) and director of the Dipartimento Farmacochimico Toss. Biol. (July 1999-December 2004 and July 2005-to date). He is responsible for ERASMUS exchanges of the Faculty of Pharmacy of the University of Palermo for the research sector Synthetic Analogues of Natural Structure of Biological Interest of the ICTPN-CNR in a scientific capacity (January 1994—December 1998). He has been Member of the Drug Discovery Committee of the European Organization for Research and Treatment of Cancer, the Societa Chimica Italiana, Member, and the International Society of Heterocyclic Chemistry (which he has also served in the capacity of vice-president for the period 2004—05). He is a scientific editor of the journal ARKIVOC. 

One of the most prominent class of multicomponent reactions involves the use of isocyanides [5] and many synthetic methods have been developed to access heterocycles from isocyanide-based chemistry [6, 7]. There are a number of reviews covering the applications of isocyanide-based MCRs in drug discovery [8, 9]. fii this review, we will focus on the most recent developments in the field. 

In addition to isocyanide-based MCRs, a wealth of highly functionalized heterocycles can be obtained from 1,3-dicarbonyl, cyanomalonate and malononitrile based MCRs [19]. These easily accessible starting materials participate in a variety of multi-component reactions and have found numerous applications in drug discovery. 

---