Selective inhibition of low affinity IgE receptor (CD23) processing: P1' bicyclomethyl substituents

S Bailey; B Bolognese; A Faller; P Louis-Flamberg; D T MacPherson; R J Mayer; L A Marshall; P H Milner; J Mistry; D G Smith; J G Ward

doi:10.1016/s0960-894x(99)00552-1

Selective inhibition of low affinity IgE receptor (CD23) processing: P1' bicyclomethyl substituents

Bioorg Med Chem Lett. 1999 Nov 1;9(21):3165-70. doi: 10.1016/s0960-894x(99)00552-1.

Authors

S Bailey¹, B Bolognese, A Faller, P Louis-Flamberg, D T MacPherson, R J Mayer, L A Marshall, P H Milner, J Mistry, D G Smith, J G Ward

Affiliation

¹ SmithKline Beecham Pharmaceuticals, UK.

PMID: 10560745
DOI: 10.1016/s0960-894x(99)00552-1

Abstract

Using a variety of alpha-hydroxy hydroxamic acid derivatives, the size and shape of the S1' pocket for the CD23 processing metalloprotease has been explored. It has been demonstrated that a P1' 2-naphthylmethyl group occupies most of the available space and gives excellent selectivity against fibroblast collagenase (matrix metalloproteinase-1, MMP-1) and other MMPs.

MeSH terms

Bridged Bicyclo Compounds / chemical synthesis*
Bridged Bicyclo Compounds / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Hydroxamic Acids / chemical synthesis*
Hydroxamic Acids / pharmacology
Matrix Metalloproteinase Inhibitors*
Molecular Structure
Receptors, IgE / antagonists & inhibitors
Receptors, IgE / metabolism*
Structure-Activity Relationship

Substances

Bridged Bicyclo Compounds
Enzyme Inhibitors
Hydroxamic Acids
Matrix Metalloproteinase Inhibitors
Receptors, IgE