Joe F. Lee

Synthesis and NK1/NK2 receptor activity of substituted-4(Z)-(methoxyimino)pentyl-1-piperazines

A series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)- (methoxyimino)pentyl-1-piperazines was prepared and their affinity for the NK1 and NK2 receptors investigated. Compounds 7f, 10o, 10r, and 10s were found to be our most potent inhibitors.

Synthesis of a series of sulfinic acid analogs of GABA and evaluation of their GABAB receptor affinities

A series of gamma-aminobutyric acid (GABA) 1 analogs was prepared in which the carboxylic acid group of GABA was replaced with a sulfinic acid group and their affinity for the GABAB receptor investigated.

The discovery of novel tartrate-based TNF-[alpha] converting enzyme (TACE) inhibitors

A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMPs. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

The synthesis of substituted fluorenes as novel non-imidazole histamine H3 inhibitors

A novel non-imidazole fluorene oxime 1a has been identified as a histamine H(3) inhibitor, and its structure-activity relationship has been evaluated.

Synthesis of substituted 4(Z)-(methoxyimino)pentyl-1-piperidines as dual NK1/NK2 inhibitors

The NK1 and NK2 receptor activity of a series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)-4(Z)-(methoxyimino)pentyl-1-piperidines was evaluated. Compounds 11d, 11e, 11f, 12a, and 12k were found to be our most potent inhibitors.