57152-17-7

Upstream product

• 57152-12-2 N-(1-benzyl-pyrrolidin-3-yl)-benzamide 
• 98-88-4 benzoyl chloride 
• 396729-75-2 1,1-dimethylethyl 3-(benzoylamino)-1-pyrrolidinecarboxylate 

Downstream Products

• 914460-64-3 N-[1-(6-nitro-quinolin-2-yl)-pyrrolidin-3-yl]-benzamide 
• 1365212-45-8 C₁₄H₁₈N₂O₂ 

Relevant academic research and scientific papers

Influence of ring size on the cognition-enhancing activity of DM235 and MN19, two potent nootropic drugs

A series of analogs of DM235 and MN19, characterized by rings with different size, have been prepared and evaluated for their nootropic activity in the mouse passive-avoidance test. It was found that the optimal ring size for the analogs of DM235, showing endocyclic both amidic groups, is 6 or 7 atoms. For the compounds structurally related to MN19, carrying an exocyclic amide group, the piperidine ring is the moiety which gives the most interesting compounds.

Novel, nonpeptidic cyanamides as potent and reversible inhibitors of human cathepsins K and L

Compounds containing a 1-cyanopyrrolidinyl ring were identified as potent and reversible inhibitors of cathepsins K and L. The original lead compound 1 inhibits cathepsins K and L with IC50 values of 0.37 and 0.45 μM, respectively. Modification of compound 1 by replacement of the quinoline moiety led to the synthesis of N-(1-cyano-3-pyrrolidinyl)benzenesulfonamide (2). Compound 2 was found to be a potent inhibitor of cathepsins K and L with a Ki value of 50 nM for cathepsin K. Replacement of the 1-cyanopyrrolidine of compound 2 by a 1-cyanoazetidine increased the potency of the inhibitor by 10-fold. This increase in potency is probably due to an enhanced chemical reactivity of the compound toward the thiolate of the active site of the enzyme. This is demonstrated when the assay is performed in the presence of glutathione at pH 7.0 which favors the formation of a GSH thiolate anion. Under these assay conditions, there is a loss of potency in the 1-cyanoazetidine series due to the formation of an inactive complex between the GSH thiolate and the 1-cyanoazetidine inhibitors. 1-Cyanopyrrolidinyl inhibitors exhibited time-dependent inhibition which allowed us to determine the association and dissociation rate constants with human cathepsin K. The kinetic data obtained showed that the increase of potency observed between different 1-cyanopyrrolidinyl inhibitors is due to an increase of kon values and that the association of the compound with the enzyme fits an apparent one-step mechanism. 13C NMR experiments performed with the enzyme papain showed that compound 2 forms a covalent isothiourea ester adduct with the enzyme. As predicted by the kinetic analysis, the addition of the irreversible inhibitor E64 to the enzyme-cyanopyrrolidinyl complex totally abolished the signal of the isothiourea bond as observed by 13C NMR, thereby demonstrating that the formation of the covalent bond with the active site cysteine residue is reversible. Finally, compound 2 inhibits bone resorption in an in vitro assay involving rabbit osteoclasts and bovine bone with an IC50 value of 0.7 μM. 1-Cyanopyrrolidine represents a new class of nonpeptidic compounds that inhibit cathepsin K and L activity and proteolysis of bone collagen.

Dipeptides which promote release of growth hormone

Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1

Selective benzoylation of primary amines in the presence of secondary amines

Compounds containing both primary and secondary amine moieties in the same molecule were treated sequentially with two equivalents of n-butyllithium at room temperature, two equivalents of TMSCI, one equivalent of n-butyllithium and one equivalent of benzoyl chloride, to afford mono-benzoylated diamines. Under these conditions, the primary amine moiety was selectively benzoylated.