Sarah Christine Hobbs

The synthesis of (+)- and (–)-epibatidine

The synthesis of the alkaloid epibatidine {exo-2-(2-chloro-5-pyridyl)-7-azabicyclo[2.2.1]heptane} in enantiomeric form involving, as the critical step, reaction or 5-lithio-2-chloropyridine with N-tert-butoxycarbonyl-7-azabicyclo[2.2.1]heptan-2-one is described.

L-708,474: the C5-cyclohexyl analogue of L-365,260, a selective high affinity ligand for the CCKB/gastrin receptor

Abstract The C5-cyclohexyl analogue of the cholecystokinin type-B (CCKB) receptor antagonist L-365,260 has been prepared. This derivative has significantly higher CCKB affinity and markedly improved CCKB/CCKA receptor selectivity (6,500 v. 87-fold) than the parent compound. It is one of the most potent and selective CCKB ligands reported to date.

POTENT, SELECTIVE, WATER-SOLUBLE BENZODIAZEPINE-BASED CCKB RECEPTOR ANTAGONISTS THAT CONTAIN LIPOPHILIC CARBOXYLATE SURROGATES

Abstract Acylsulphonamide analogues of the meta-tolylurea L-708,474 have been synthesised and evaluated as CCKB receptor antagonists. Such derivatives retain very high affinity and subtype selectivity for the CCKB receptor, and have good aqueous solubility. The ortho-tolyl acylsulphonamide L-736,309 is orally bioavailable and brain penetrant in rat.

ENANTIOMERIC SEPARATION OF A SERIES OF 1,4-BENZODIAZEPIN-2-ONE CCK B RECEPTOR ANTAGONISTS BEARING ACIDIC SUBSTITUENTS BY CHIRAL HPLC

A series of 1,4-benzodiazepin-2-one CCKB receptor antagonists are reported in which substitution at C3 of the benzodiazepine by a phenyl-urea group bearing acidic moieties has generated a chiral centre. As one of these enantiomers is substantially more selective for the CCKB over the CCKA receptor, an analytical separation of the enantiomers was developed to monitor the resolution of compounds by chemical means. It was shown that such compounds may be resolved using a Pirkle-type 3,5-dinitrobenzoyl-leucine chiral stationary phase to give high α and RS values. However, traditional mobile phase methodologies proved unsuccessful with these compounds which were found not to elute without the addition of acetic acid. An investigation is described in which the effect of the acidic substituent, mobile phase composition, including addition of acid, and temperature is discussed for such compounds.