300804-20-0

Upstream product

• 637-59-2 1-Bromo-3-phenylpropane 
• 2802-06-4 iminodiacetic acid hydrochloride 
• 142-73-4 iminodiacetic acid 
• 2038-57-5 3-Phenylpropan-1-amine 
• 79-11-8 chloroacetic acid 

Downstream Products

• 1333227-44-3 (S)-2-{2-[carboxymethyl-(3-phenyl-propyl)-amino]-acetylamino}-3-(1H-imidazol-4-yl)-propionic acid methyl ester. 
• 1333227-66-9 ((((S)-2-(1H-imidazol-4-yl)-1-methylcarbamoyl-ethylcarbamoyl)-methyl)-(3-phenyl-propyl)-amino)-acetic acid 
• 1333228-14-0 [{[(S)-1-Methylcarbamoyl-2-(1-trityl-1H-imidazol-4-yl)-ethylcarbamoyl]-methyl}-(3-phenyl-propyl)-amino]-acetic acid methyl ester 
• 1333227-91-0 [Methoxycarbonylmethyl-(3-phenyl-propyl)-amino]-acetic acid 
• 1490613-08-5 C₁₃H₁₅NO₃ 
• 1333227-01-2 (S)-2-{2-[Carboxymethyl-(3-phenyl-propyl)-amino]-acetylamino}-3-(1-trityl-1H-imidazol-4-yl)-propionic acid methyl ester 
• 1333227-57-8 CH₂O₂*C₂₃H₃₂N₄O₅ 
• 1333227-28-3 CH₂O₂*C₂₆H₃₁N₅O₄ 
• 1333227-32-9 CH₂O₂*C₂₁H₂₆N₆O₄ 
• 1333227-24-9 CH₂O₂*C₁₉H₂₆N₄O₄ 
• 1333228-07-1 [{[(S)-1-Methylcarbamoyl-2-(1-trityl-1H-imidazol-4-yl)-ethylcarbamoyl]-methyl}-(3-phenyl-propyl)-amino]-acetic acid 
• 1604818-19-0 C₂₆H₃₂N₂O₈Pd 

Relevant academic research and scientific papers

Structure-activity relationships of imidazole-derived 2-[ N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme

Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-a and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-a clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE's role.

Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-β hydrolysis

Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels.

Nickel(II) complexes with N-aralkyliminodiacetic acids: Preparation, spectroscopic, structural and thermal characterization

The reactions of N-aralkyl derivatives of iminodiacetic acid (H 2Bnida, H2Peida, H2Ppida, o-H2Cbida, Bn = benzyl, Pe = 2-phenylethyl, Pp = 3-phenylprop-1-yl, o-Cb = o-chlorobenzyl) with nickel(II) chloride hexahydrate or nickel(II) acetate tetrahydrate in aqueous solutions were studied. Five new nickel(II) complexes [Ni(Bnida)(H 2O)3]·H2O (1), [Ni(Peida)(H 2O)3] (2), [Ni(Ppida)(H2O)3] ·H2O (3a), [Ni(Ppida)(H2O)3] (3b) and [Ni(o-Cbida)(H2O)3] (4) were prepared and characterized by infrared spectroscopy and thermal analysis (TGA-DTA). The crystal structures of 1 and 3b were determined by single-crystal X-ray structural analysis. The octahedral coordination environment around the nickel(II) ion in 1 and 3b consists of an O,N,O′-tridentate N-aralkyliminodiacetate ion and three water molecules arranged in a fac-position. The molecules in the crystal structures of 1 and 3b are connected into a complicated hydrogen-bonded 2D network, dominated by the O-H?O hydrogen bonds. These 2D networks are in turn assembled into a 3D architecture only by weak van der Waals interactions.

Ligands of insulin degrading enzyme and their uses

The invention relates to ligands of insulin degrading enzyme and to their uses. The ligands of the invention are non peptidic and bind specifically to the exosite of insulin degrading enzyme. They are useful, in particular a use in the pharmaceutical field.