Several pteridine analogues 4-13, 23-26 have been synthesized and tested in vitro against three cancer cell lines, MCF7 (breast), NCI-H460 (lung) and SF-268 (CNS). All tested pteridines can serve as novel templates for the anticancer chemotherapy and can serve as new leads in cancer chemotherapy.

This paper describes the synthesis and physical and biological effects of introducing different substituents at the alpha-position of the tryptophan containing neurokinin-1 receptor antagonist [(R)-2-(1H-indol-3-yl)-1-methyl-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (CI 1021). The described compounds all exhibit less than 5 nM binding affinities for the human neurokinin-1 receptor and selectivity over the tachykinin NK(2) and NK(3) receptor subtypes. Application of variable temperature nuclear magnetic resonance spectroscopy studies of the amide and urethane protons was utilized to determine the existence of an intramolecular hydrogen bond. This intramolecular hydrogen bond increases the apparent lipophilicity to allow increased central nervous system penetration and pharmacological activity (gerbil foot tap test) in the case of the highest affinity compound [(S)-1-dimethylaminomethyl-2-(1H-indol-3-yl)-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (PD 174424) over those analogues that could not form an intramolecular hydrogen bond.

Simple purification of compounds can be achieved using a bipyridine unit as a tag and resin-bound metal ions. The usefulness of this method (see scheme) is demonstrated by the multistep synthesis of a small library of hydantoins and benzodiazepines.

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Aromatic, aliphatic and sterically hindered amines react smoothly with commercially available N,N'-bis-BOC-S-methylisothiourea 2 in the presence of mercury chloride to give the protected guanidine in good yield. It is particularly noteworthy that 2 can also be employed in a straightforward, two-step synthesis of monoaryl internal guanidines.

Omega-conotoxin MVIIA, a highly potent antagonist of the N-type voltage sensitive calcium channel, has shown utility in several models of pain and ischemia. We report a series of three alkylphenyl ether based analogues which mimic three key amino acids of the toxin. Two of the compounds have been found to exhibit IC50 values of 2.7 and 3.3 microM at the human N-type voltage sensitive calcium channel.

Three mimetics of the peptide ω-Conotoxin MVIIA have been synthesised following the dendroid approach. The three key central amino acids of the natural peptide are mimicked by phenylguanidine (arginine), isopentyl (leucine) and aryl alcohol (tyrosine) attached to a quinolinone core at the 1- and 8-positions. The derivatives are designed to position these key groups in similar spatial orientation to that of the natural peptide in a structure that will have limited conformational flexibility. Key steps of the syntheses involve selective N-alkylation of quinolinone derivatives and guanylation of aryl amines.