65415-04-5

Upstream product

• 67-56-1 methanol 
• 103-82-2 phenylacetic acid 
• 73724-45-5 N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine 
• 5680-80-8 methyl (2S)-2-amino-3-hydroxypropanoate hydrochloride 
• 536-74-3 phenylacetylene 
• 5619-04-5 methyl 2-amino-3-hydroxypropanoate hydrochloride 
• 103-80-0 phenylacetyl chloride 

Downstream Products

• 88144-06-3 α-N-phenylacetyl-L-serine hydroxamic acid 
• 223560-31-4 N-[2-hydroxy-1-(1-hydroxymethyl)ethyl]phenylacetamide 
• 1068658-30-9 (3S)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-5H-oxazolo[3,2-a]pyridine-3-carboxylic acid methyl ester 
• 246535-25-1 N-(1-methyl-3-oxo-pyrazolidin-4-yl)-2-phenyl-acetamide 
• 21149-16-6 N-(Phenylacetyl)dehydroalanine methyl ester 
• 95545-31-6 O-benzoyl-α-N-phenylacetylserine hydroxamate 
• 95545-32-7 Acetic acid (S)-2-oxo-3-phenylacetylamino-azetidin-1-yl ester 

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.

Toward the development of chemoprevention agents. Part 1: Design, synthesis, and anti-inflammatory activities of a new class of 2,5-disubstituted-dioxacycloalkanes

A new class of 2,5-disubstituted-dioxacycloalkanes were designed and synthesized via stereoselective synthetic method as cancer chemoprevention agents. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Some of these compounds exhibited comparable or better anti-inflammatory activities than that of aspirin suggesting that they can be further developed as potential anti-inflammatory drug lead compounds. In addition, treatment of these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds.

Toward the development of chemoprevention agents. Part II: Chemo-enzymatic synthesis and anti-inflammatory activities of a new class of 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes

A new series of optically pure 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes were designed and synthesized via a chemo-enzymatic combined method to develop new chemoprevention agents. Twenty-four of newly synthesized compounds significantly inhibited xylene-induced rat ear edema and exhibited comparable or better anti-inflammatory activities than the reference drug aspirin. Treatment of these anti-inflammatory agents did not prolong the tail bleeding time in rat. In addition, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes exhibited good membrane permeability based on in vitro Caco-2 cell monolayer permeability assay. Furthermore, some preliminary structure-activity relationships were further analyzed among these compounds. Taken together, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes may represent a new class of anti-inflammatory drugs with safer pharmacological profile.

Synthesis of pyrazolidinone antibacterial agents

The synthesis of monocyclic pyrazolidinones, which show moderate antibacterial activity, are described.