426844-22-6

Usage

Molecular weight

257.31 g/mol

Structure

A pyrrolidine ring with a carboxyl group, an aminocarbonyl group, a fluorine atom, and a Boc-protecting group (1,1-dimethylethyl ester)

Boc-protected

The amino group is protected by a Boc (tert-butyloxycarbonyl) group, which is important for preventing unwanted side reactions during peptide synthesis.

Fluoromethyl ketone amino acid derivative

The presence of a fluorine atom on the carbonyl group makes it a fluoromethyl ketone derivative, which can influence the properties and reactivity of the compound.

Applications

Drug development, pharmaceutical research, peptide synthesis, key building block in medicinal chemistry, preparation of antiviral and antineoplastic agents, precursor in the synthesis of complex molecules for biological studies and drug discovery.

Stereochemistry

The compound has two chiral centers (2S and 4S), which indicates that it has a specific three-dimensional arrangement of atoms, important for its biological activity and selectivity.

Upstream product

• 40216-83-9 L-4-hydroxyproline methyl ester hydrochloride 
• 203866-16-4 1-tert-butyl 2-methyl (2S,4S)-4-fluoropyrrolidine-1,2-dicarboxylate 

Downstream Products

• 483366-11-6 (2S,4S)-4-fluoropyrrolidine-2-carbonitrile; 4-methylbenzene-1-sulfonic acid 
• 1064078-39-2 (4S)-fluoro-L-prolinamide p-toluenesulfonate 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors

A series of novel hetero-aromatic moieties substituted α-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure-activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004-113.6 μM). Moreover, compounds 6h (IC50 = 0.004 μM) and 6n (IC50 = 0.01 μM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t1/2 = 1.45 h; compound 6n, F% = 16.8%, t1/2 = 3.64 h).

Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2- carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors

Based on the previous work in our group and the principle of computer-aided drug design, a series of novel β-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 8l had moderate DPP4 inhibitory activity (IC50 = 0.05 μM) and good oral bioavailability (F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC50 = 0.01 μM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles (F = 22.8%, t1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9.

Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes

A novel series of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2- carbonitrile derivatives was designed, synthesized, and found to act as dipeptidyl peptidase-4 (DPP-4) inhibitors. From this series of compounds, compound 17a was identified as an efficacious, safe, and selective inhibitor of DPP-4. In vivo studies in ICR and KKAy mice showed that administration of this compound resulted in decreased blood glucose in these mice after an oral glucose challenge. Compound 17a showed high DPP-4 inhibitory activity (IC50 = 0.017 μM), moderate selectivity against DPP-4 (selective ratio: DPP-8/DPP-4 = 1324; DPP-9/DPP-4 = 1164), and good efficacy in oral glucose tolerance tests in ICR and KKAy mice. These in vivo anti-diabetic properties and its desirable pharmacokinetic profile in Sprague-Dawley rats demonstrate that compound 17a is a promising candidate for development as an anti-diabetic agent.

OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF

The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.