78348-56-8

Upstream product

• 2133-40-6 methyl pyrrolidine-2-carboxylate hydrochloride 
• 103-80-0 phenylacetyl chloride 
• 2133-40-6 L-proline methyl ester monohydrochloride 
• 536-74-3 phenylacetylene 
• 67-56-1 methanol 
• 103-82-2 phenylacetic acid 
• 71989-31-6 Fmoc-Pro-OH 
• 100-52-7 benzaldehyde 
• 2700-22-3 Benzylidenemalononitrile 
• 1867-37-4 Benzylmalononitrile 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 147-85-3 L-proline 
• 2752-38-7 N-phenylacetyl-L-proline 

Downstream Products

• 122000-64-0 1-Phenylacetyl-pyrrolidine-2-carboxylic acid amide 
• 1337550-90-9 (S)-1-(2-{2'-[2-((S)-2-oxo-2-pyrrolidin-1-yl-ethyl)biphenyl-2-yl]acetyl}pyrrolidine)-2-carboxylic acid methyl ester 
• 1312609-13-4 C₄₂H₄₀N₄O₄ 
• 1312609-12-3 C₃₆H₃₆N₄O₄ 
• 1312609-11-2 C₃₅H₄₁N₅O₆ 
• 1312611-12-3 C₂₃H₂₃N₃O₂ 
• 1312611-10-1 C₂₉H₂₇N₃O₂ 
• 1312611-09-8 C₃₄H₃₅N₃O₄ 
• 1312611-08-7 C₁₉H₂₁BN₂O₄ 
• 1312611-01-0 C₂₆H₂₆N₄O₃ 
• 1312611-00-9 C₂₆H₂₄N₄O₅ 
• 1312609-05-4 C₃₉H₃₉N₅O₅ 
• 2752-38-7 (S)-1-(2-phenylacetyl)pyrrolidine-2-carboxylic acid 
• 95568-74-4 (S)-1-(2-phenylethyl)pyrrolidin-2-ylmethanol 

Relevant academic research and scientific papers

Ruthenium-Catalyzed Oxidative Amidation of Alkynes to Amides

Complex CpRuCl(PPh3)2 catalyzes reactions of terminal alkynes with 4-picoline N-oxide and primary and secondary amines to afford the corresponding amides. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry. Stoichiometric studies reveal that the true catalysts of the processes are the vinylidene cations [CpRu(=C=CHR)(PPh3)2]+ which are oxidized to the Ru(η2-CO)-ketenes by the N-oxide. Finally, nucleophilic additions of primary and secondary amines to the free ketenes yield the corresponding amides.

Lipophilic Permeability Efficiency Reconciles the Opposing Roles of Lipophilicity in Membrane Permeability and Aqueous Solubility

As drug discovery moves increasingly toward previously "undruggable" targets such as protein-protein interactions, lead compounds are becoming larger and more lipophilic. Although increasing lipophilicity can improve membrane permeability, it can also incur serious liabilities, including poor water solubility, increased toxicity, and faster metabolic clearance. Here we introduce a new efficiency metric, especially relevant to "beyond rule of 5" molecules, that captures, in a simple, unitless value, these opposing effects of lipophilicity on molecular properties. Lipophilic permeability efficiency (LPE) is defined as log D7.4dec/w - mlipocLogP + bscaffold, where log D7.4dec/w is the experimental decadiene-water distribution coefficient (pH 7.4), cLogP is the calculated octanol-water partition coefficient, and mlipo and bscaffold are scaling factors to standardize LPE values across different cLogP metrics and scaffolds. Using a variety of peptidic and nonpeptidic macrocycle drugs, we show that LPE provides a functional assessment of the efficiency with which a compound achieves passive membrane permeability at a given lipophilicity.

Sterically Demanding Oxidative Amidation of α-Substituted Malononitriles with Amines Using O2

An efficient amidation method between readily available 1,1-dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α-peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α-carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.

B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether

The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.

Oxidative C-H homodimerization of phenylacetamides

A range of secondary and tertiary phenylacetamides undergo oxidative homodimerization to afford biaryls. The reaction proceeds under palladium catalysis in the presence of a copper cocatalyst and oxygen and is most effective for electron-rich substrates.

NOVEL INHIBITORS OF HEPATITIS C VIRUS REPLICATION

The embodiments provide compounds of the general Formulae I, II, III, IV, or V as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Design, synthesis, and biological evaluation of novel T-Type calcium channel antagonists

This paper describes the synthesis of several novel T-type calcium channel antagonists that inhibit calcium influx into the cell, which in turn regulates unknown aspects of the cell cycle pathway that are responsible for cellular proliferation. A library of compounds was synthesized anda brief structure activity relationship will be described. From these studies we have identified a compound (1) that displays anti-proliferative activity in the low micromolar range across a variety of cancer cell lines.

NOVEL BIOLOGICALLY ACTIVE COMPOUND HAVING ANTI-PROLYL ENDOPEPTIDASE ACTIVITY

A novel compound that exhibits inhibitory activity against prolyl endopeptidase and a method for chemical synthesis of said compound, as well as its use as a prolyl endopeptidase inhibitor and an anti-amnesic agent that contains said compound as the activ