855959-40-9

Basic information

• Product Name: (2R)-N-(2-aminophenyl)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanamide
• Synonyms: (2R)-N-(2-aminophenyl)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanamide
• CAS NO: 855959-40-9
• Molecular Weight: 436.554
• Mol File: 855959-40-9.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: (2R)-N-(2-aminophenyl)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanamide(CAS DataBase Reference)
• NIST Chemistry Reference: (2R)-N-(2-aminophenyl)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanamide(855959-40-9)
• EPA Substance Registry System: (2R)-N-(2-aminophenyl)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanamide(855959-40-9)

Safety Data

• Hazardous Substances Data: 855959-40-9(Hazardous Substances Data)

Upstream product

• 855959-31-8 (4S)-4-benzyl-3-[(2R)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanoyl]-1,3-oxazolidin-2-one 
• 855959-36-3 (2R)-3-(benzyloxy)-2-([1,1'-biphenyl-4-yl]methyl)propanoic acid 
• 95-54-5 1,2-diamino-benzene 
• 313467-78-6 (4S)-4-benzyl-3-(3-[1,1'-biphenyl-4-yl]propanoyl)-1,3-oxazolidin-2-one 
• 35888-99-4 3-(4-biphenylyl)propionic acid 
• 3587-60-8 Benzyloxymethyl chloride 

Downstream Products

• 855959-59-0 S-[(2S)-2-(1H-benzimidazol-2-yl)-3-[1,1'-biphenyl-4-yl]propyl] ethanethioate 
• 855959-54-5 (2S)-2-(1H-benzimidazol-2-yl)-3-[1,1'-biphenyl-4-yl]propan-1-ol 
• 855959-49-8 2-[(1S)-2-(benzyloxy)-1-([1,1'-biphenyl-4-yl]methyl)ethyl]-1H-benzimidazole 

Relevant articles and documents

Second-generation inhibitors for the metalloprotease neprilysin based on bicyclic heteroaromatic scaffolds: Synthesis, biological activity, and X-ray crystal-structure analysis

A new class of nonpeptidic inhibitors of the ZnII-dependent metalloprotease neprilysin with IC50 values in the nanomolar activity range (0.034-0.30 μM) were developed based on structure-based de novo design (Figs. 1 and 2). The inhibitors feature benzimidazole and imidazo[4,5-c] pyridine moieties as central scaffolds to undergo H-bonding to Asn542 and Arg717 and to engage in favorable π-π stacking interactions with the imidazole ring of His711. The platform is decorated with a thiol vector to coordinate to the ZnII ion and an aryl residue to occupy the hydrophobic S1′ pocket, but lack a substituent for binding in the S2′ pocket, which remains closed by the side chains of Phe106 and Arg110 when not occupied. The enantioselective syntheses of the active compounds (+)-1, (+)-2, (+)-25, and (+)-26 were accomplished using Evans auxiliaries (Schemes 2,4, and 5). The inhibitors (+)-2 and (+)-26 with an imidazo[4,5-c]pyridine core are ca. 8 times more active than those with a benzimidazole core ((+)-1 and (+)-25) (Table 1). The predicted binding mode was established by X-ray analysis of the complex of neprilysin with (+)-2 at 2.25-A resolution (Fig. 4 and Table 2). The ligand coordinates with its sulfanyl residue to the ZnII ion, and the benzyl residue occupies the S1′ pocket. The 1H-imidazole moiety of the central scaffold forms the required H-bonds to the side chains of Asn542 and Arg717. The heterobicyclic platform additionally undergoes π-π stacking with the side chain of His711 as well as edge-to-face-type interactions with the side chain of Trp693. According to the X-ray analysis, the substantial advantage in biological activity of the imidazopyridine inhibitors over the benzimidazole ligands arises from favorable interactions of the pyridine N-atom in the former with the side chain of Arg102. Unexpectedly, replacement of the phenyl group pointing into the deep S1′ pocket by a biphenyl group does not enhance the binding affinity for this class of inhibitors.