Partial characterization of 5-fluoropyrimidine-resistant mutants of Neurospora crassa

Summary The primary lesion in a number of 5-fluoropyrimidine resistant mutants of Neurospora crassa has been identified. ud-1 mutants, previously designated fdu-2, are deficient in nucleoside uptake and show extensive intragenic complementation. uc-4 mutants lack uracil phosphoribosyl transferase with no complementation between 23 alleles. udk mutants lack uridine kinase activity. fdu-2 mutants affect the repression of the first two de novo pyrimidine biosynthetic enzymes, have no detectable uridine kinase activity and show decreased uridine uptake. Accordingly, fdu-2 may be involved in the regulation of pyrimidine uptake, salvage and de novo synthesis.Supported by S.R.C. grant GR/A/64655F. Buxton was supported during the period of this work by an S.R.C. Research Studentship     

7-Azaindole-3-acetic acid derivatives: Potent and selective CRTh2 receptor antagonists

High throughput screening identified a 7-azaindole-3-acetic acid scaffold as a novel CRTh2 receptor antagonist chemotype, which could be optimised to furnish a highly selective compound with good functional potency for inhibition of human eosinophil shape change in whole blood and oral bioavailability in the rat.