Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones.

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.

Affinity prediction for substrates of the peptide transporter PepT1.

A quantitative method has been developed for determining the affinity of substrates for the peptide transporter PepT1, allowing oral availability of drugs via PepT1 to be estimated.

Probing dipeptide trans/cis stereochemistry using pH control of thiopeptide analogues, and application to the PepT1 transporter.

The stereochemistry of thiodipeptides of proline [e.g. Ala-Psi[CS-N]-Pro] can be controlled using pH, allowing the trans-preference for substrates of the peptide transporter PepT1 to be confirmed.

Conformational and spacial preferences for substrates of PepT1.

The conformation at the first residue of dipeptide substrates for the peptide transporter PepT1 has been probed using constrained peptide analogues, and the active conformation has been identified.