1013405-02-1

Basic information

• Product Name: (2S,2′S)-N,N'-([1,1′-biphenyl]-4,4′-diyl)bis(pyrrolidine-2-carboxamide)
• Synonyms: (2S,2′S)-N,N'-([1,1′-biphenyl]-4,4′-diyl)bis(pyrrolidine-2-carboxamide)
• CAS NO: 1013405-02-1
• Molecular Weight: 378.474
• Mol File: 1013405-02-1.mol

Chemical Properties

• CAS DataBase Reference: (2S,2′S)-N,N'-([1,1′-biphenyl]-4,4′-diyl)bis(pyrrolidine-2-carboxamide)(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,2′S)-N,N'-([1,1′-biphenyl]-4,4′-diyl)bis(pyrrolidine-2-carboxamide)(1013405-02-1)
• EPA Substance Registry System: (2S,2′S)-N,N'-([1,1′-biphenyl]-4,4′-diyl)bis(pyrrolidine-2-carboxamide)(1013405-02-1)

Safety Data

• Hazardous Substances Data: 1013405-02-1(Hazardous Substances Data)

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 92-87-5 p,p'-diaminobiphenyl 
• 1512624-36-0 (2S,2′S)-di-tert-butyl 2,2′-(([1,1′-biphenyl]4,4′diylbis(azanediyl))bis(carbonyl))bis(pyrrolidine-1-carboxylate) 

Downstream Products

• 1512624-44-0 dimethyl ((1R,1′R)-((2S,2′S)-(([1,1′-biphenyl]-4,4′-diylbis(azanediyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl))dicarbamate 

Relevant articles and documents

Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches

Here we report a series of potent anti-HCV agents bearing a symmetrical benzidine l-prolinamide backbone with different capping groups including alkyl/aryl carbamates of natural and unnatural valine and leucine amino acids. All compounds were investigated for their inhibitory activity in an HCV replicon assay on genotype 1b. The novel compounds share some chemical and clinical attributes of commercially available NS5A inhibitors. Compounds 5 and 6 with unnatural capping residue and ethyl and isobutyl carbamates showed EC50 values in the picomolar range with a low toxicity profile and selectivity indices of several orders of magnitude. These findings enlarge the chemical space from which NS5A inhibitors may be discovered by adopting unnatural amino acids, amino acids other than valine and carbamates other than methyl as the capping groups.

Symmetric benzidine derivatives as anti-HCV agents: Insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates

Novel symmetric molecules, bearing a benzidine prolinamide core, two terminal carbamate caps of variable sizes and nature, including natural and unnatural amino acids were developed. Several terminal N-carbamate substituents of the core structure, ranging from linear methyl, ethyl and butyl groups to branching isobutyl group; and an aromatic substituent were also synthesized. Series 1 has hydrophobic AA residues, namely S and R phenylglycine and a terminal carbamate capping group, whereas Series 2 bears sulphur containing amino acids, specifically S and R methionine and the natural R methylcysteine. The novel compounds were tested for their inhibitory activity (EC50) and their cytotoxicity (CC50), using an HCV 1b (Con1) reporter replicon cell line. Compound 4 with the unnatural capping residue, bearing D-Phenylglycine amino acid residue and N-isobutyloxycarbonyl capping group, was the most active within the two series, with EC50 = 0.0067 nM. Moreover, it showed high SI50 > 14788524 and was not cytotoxic at the highest tested concentration (100 μΜ), indicating its safety profile. Compound 4 also inhibited HCV genotypes 2a, 3a and 4a. Compared to the clinically approved NS5A inhibitor Daclatasvir, compound 4 shows higher activity against genotypes 1b and 3a, as well as improved safety profile.

Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors

Our study describes the discovery of a series of highly potent hepatitis C virus (HCV) NS5A inhibitors based on symmetrical prolinamide derivatives of benzidine and diaminofluorene. Through modification of benzidine, l-proline, and diaminofluorene derivatives, we developed novel inhibitor structures, which allowed us to establish a library of potent HCV NS5A inhibitors. After optimizing the benzidine prolinamide backbone, we identified inhibitors embedding meta-substituted benzidine core structures that exhibited the most potent anti-HCV activities. Furthermore, through a battery of studies including hERG ligand binding assay, CYP450 binding assay, rat plasma stability test, human liver microsomal stability test, and pharmacokinetic studies, the identified compounds 24, 26, 27, 42, and 43 are found to be nontoxic, and are expected to be effective therapeutic anti-HCV agents.

Synthesis and biological evaluation of novel bis-aromatic amides as novel PTP1B inhibitors

A series of bis-aromatic amides was designed, synthesized, and evaluated as a new class of inhibitors with IC50 values in the micromolar range against protein tyrosine phosphatase 1B (PTP1B). Among them, compound 15 displayed an IC50 value of 2.34 ± 0.08 μM with 5-fold preference over TCPTP. More importantly, the treatment of CHO/HIR cells with compound 15 resulted in increased phosphorylation of insulin receptor (IR), which suggested extensive cellular activity of compound 15. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.