Considering the importance of nitrogen-rich heterocycles in drug discovery, a novel strategy towards heterocycle synthesis was envisioned using cyanamide chemistry. Synthesis which involve mild conditions, avoids multi-step sequence and non-toxic reagents are desirable for generation of large combinatorial libraries of drug molecules. We envisaged that the NCN linkage of the cyanamide as well as the concomitant use of the nucleo-and electrophilic centres of the cyanamide could provide a novel synthetic route towards nitrogen heterocycles. The first part (Ch-2) constitute the bulk of the thesis and it focuses on the generation of cyanamide ion and its cyclisative capture with a 1,3-dipole – nitrile oxide in situ. The cycloadduct -1,2,4-oxadiazol-5(4H)-imine was obtained in good yields, which was further transformed into pharmacologically important cores like oxadiazolone and amidines. A library of the different heterocyclic cores was generated, which tolerated a wide variety of functional groups in good to excellent yields. In the second part (Ch-3), we developed a novel protocol for the synthesis of 1,2,4-triazol-3-imine via a formal 1,3-dipolar cycloaddition of in situ generated nitrile imines and cyanamide ion. Further hydrolysis furnished with 1,2,4-triazol-3-one, which is an important core from medicinal chemistry point of view. The concomitant generation and reaction of two reactive species- 1,3-dipoles and cyanamide ion was achieved in a single pot in situ to provide a route towards novel and pharmaceutically important heterocyclic cores. The present work provides a platform for the development of cyanamide derivatives as a ‘single-reagent—diverse-scaffolds’ strategy for time efficient library delivery of structurally diverse molecules.

The work presented is a substantial addition to the established methods of analysing the data generated by gas chromatography and low-resolution mass spectrometry. It has applications where these techniques are used on a large scale for screening complex mixtures, including urine samples for sports drug surveillance. The analysis of such data is usually automated to detect peaks in the chromatograms and to search a library of mass spectra of banned or unwanted substances. The mass spectra are usually not exactly the same as those in the library, so to avoid false negatives the search must report many doubtful matches. Nearly all the samples in this type of screening are actually negative, so the process of checking the results is tedious and time-consuming. A novel method, called scaled subtraction, takes each scan from the test sample and subtracts a mass spectrum taken from a second similar sample. The aim is that the signal from any substance common to the two samples will be eliminated. Provided that the second sample does not contain the specified substances, any which are present in the first sample can be more easily detected in the subtracted data. The spectrum being subtracted is automatically scaled to allow for compounds that are common to both samples but with different concentrations. Scaled subtraction is implemented as part of a systematic approach to preprocessing the data. This includes a new spectrum-based alignment method that is able to precisely adjust the retention times so that corresponding scans of the second sample can be chosen for the subtraction. This approach includes the selection of samples based on their chromatograms. For this, new measures of similarity or dissimilarity are defined. The thesis presents the theoretical foundation for such measures based on mass spectral similarity. A new type of difference plot can highlight significant differences. The approach has been tested, with the encouraging result that there are less than half as many false matches compared with when the library search is applied to the original data. True matches of compounds of interest are still reported by the library search of the subtracted data.