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.     

Bringing the visiting diary up to date.

A method is described for the systematic assessment and review of long term dependent patients in a small practice using a personally developed computer program and assessment scale.     

Temperature sensitivity of the sodium pump in red cells from various hibernator and non-hibernator species

Summary Ouabain-sensitive K influx was measured at 5°C and 37°C in red cells from seven species of mammals known to hibernate, and nine species of non-hibernators. Care was taken to saturate the internal and external cation sites of the sodium pump, and maintain the cell metabolism. Species variation in ouabain-resistance among rodents was also taken into account. In six out of seven species of hibernators the pump was relatively insensitive to lowering the temperature, the ratio of activity at 5°C/37°C being >1.8%. By contrast eight of the nine non-hibernator species gave a ratio <1.8%. The two exceptions were the hamster, which gave a ratio of 0.8% as a hibernator, and the mole which gave a ratio of 3% as a non-hibernator. No similar correlation was observed for the ouabain-insensitive K influx, in either groups of animals. It is concluded that cold tolerance of the sodium pump is a general but not essential property of hibernator red cells.     

The sequence around the phosphorylation site of the porcine heart type phosphorylase isoenzyme

1. A tetradecapeptide containing the phosphorylation site was obtained from 32P-labelled pig heart phosphorylase a isoenzyme by alpha-chymotryptic digestion. 2. The peptide was purified by Mono S cation-exchange chromatography and reversed-phase HPLC. 3. The phosphorylated residue was identified as Ser and the sequence was determined: T D G E R R K Q I S V R G L. 4. The sequence was compared to the known sequences of muscle and liver type isophosphorylases and the structural consequences of the amino acid residue exchanges were predicted.