Discovery of pyrroloimidazoles as agents stimulating neurite outgrowth

A diverse library of substituted pyrroloimidazoles was assembled by a multicomponent reaction (MCR) of tosylmethyl isocyanides (TOSMIC), indole carbaldehydes and primary amines in a van Leusen reaction. A library of this scaffold was screened in a phenotypic assay for neurite outgrowth. Several members of this library where found to promote neurite outgrowth. The combinatorial synthesis of the library is presented. Such small molecules will serve as useful chemical probes to study neurite growth and may ultimately lead to a therapeutic application for axon regeneration of lesions of the human spinal cord and brain.