470461-86-0

Upstream product

• 23429-44-9 4-methyltrityl chloride 
• 2372-51-2 4-(aminomethyl)-3-nitrobenzoic acid 
• 55715-03-2 4-bromomethyl-3-nitrobenzoic acid 

Downstream Products

• 470461-87-1 3-Amino-4-({[(4-methylphenyl)diphenylmethyl] amino}methyl)benzoic Acid 

Relevant academic research and scientific papers

Syntheses and Activities of New C10 β-Turn Peptidomimetics

A program to identify small molecules that mimic or disrupt protein-protein interactions led us to design the peptidomimetics 1-3. Solid-phase syntheses of 1-3 were developed. The purities of the crude materials isolated from the resin tend to be highest for the S- and N-compounds 2 and 3 and better than in the corresponding syntheses of peptidomimetics A. The particular dipeptide units incorporated were chosen to correspond with the turn regions of the neurotrophins (e.g., nerve growth factor {NGF} and the neurotrophin factor-3 {NT-3}). Preliminary studies were performed to access the binding of these analogues to Trk receptors and their ability to induce cell survival (just as NGF and NT-3 do). Several active compounds were identified. However, poor water solubilities of some of the other compounds preclude reliable testing. Consequently, solid-phase modifications to the synthetic procedures were investigated to provide access to the derivatives 12-14 in which the aromatic nitro group is replaced by amine, guanidine, or sulfonamide functionalities. The latter are more acceptable pharmacophores than nitro groups and also tend to increase the water solubilities of the peptidomimetics.

New templates for syntheses of ring-fused, C10 β-turn peptidomimetics leading to the first reported small-molecule mimic of neurotrophin-3

β-Turn peptidomimetics 1 were designed to mimic hot spots of neurotrophin-3 (NT-3) and others. Solid-phase syntheses of these were developed, though limitations were encountered with scale-up. Consequently, an alternative design with 2 was investigated. 1 and 2 favored distorted type I β-turn conformations in solution. It was found that peptidomimetic 2b has NT-3-like neurotrophic activity in cell survival assays, selectively binds the NT-3 receptor TrkC, and induces the tyrosine phosphorylation of the TrkC receptor.