104730-75-8

Upstream product

• 2756-87-8 methyl hydrogen fumarate 
• 100-39-0 benzyl bromide 
• 624-49-7 dimethylfumarate 

Downstream Products

• 362485-22-1 C₁₄H₁₇NO₄ 
• 1313282-34-6 3-benzyl 4-methyl trans-1-benzylpyrrolidine-3,4-dicarboxylate 
• 1313282-34-6 3-benzyl 4-methyl trans-1-benzylpyrrolidine-3,4-dicarboxylate 

Relevant academic research and scientific papers

Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists

A screen conducted with nearly 100000 compounds and a surrogate functional assay for stimulation of an immune response that measured the release of TNF-α from treated human THP-1 myeloid cells differentiated along the macrophage line led to the discovery of the diprovocims. Unique to these efforts and of special interest, the screening leads for this new class of activators of an immune response came from a compound library designed to promote cell-surface receptor dimerization. Subsequent comprehensive structure-activity relationship studies improved the potency 800-fold over that of the screening leads, providing diprovocim-1 and diprovocim-2. The diprovocims act by inducing cell-surface toll-like receptor (TLR)-2 dimerization and activation with TLR1 (TLR1/TLR2 agonist), bear no structural similarity to any known natural or synthetic TLR agonist, and are easy to prepare and synthetically modify, and selected members are active in both human and murine systems. The most potent diprovocim (3, diprovocim-1) elicits full agonist activity at extraordinarily low concentrations (EC50= 110 pM) in human THP-1 cells, being more potent than the naturally derived TLR1/TLR2 agonist Pam3CSK4 or any other known small molecule TLR agonist.

DIPROVOCIMS: A NEW AND POTENT CLASS OF TLR AGONISTS

A diprovocim compound that corresponds in structure to structural Formula V is disclosed, wherein A, W, Z, R1, R2, R3 and R4 (when present) are defined within. A diprovocim compound has immune-adjuvant properties on human and mouse cells in culture and on in vivo immunization of mice. A composition containing a diprovocim and a method of using a compound are also disclosed. The immunostimulatory activity of a diprovocim compound is similar to that of LPS, to which there is no apparent structural similarity. A contemplated compound bears no structural similarity to either the TLR1/TLR2 lipoprotein agonists nor to any other synthetic TLR agonist, and is remarkably easy to prepare and synthetically modify.