Process Development and Scale-Up of a Novel Atypical DAT Inhibitor ()-CE-123.

Large-scale syntheses of small molecules and kilo laboratories are crucial steps in drug development, especially in advanced stages. ()-5-((Benzhydrylsulfinyl)methyl)thiazole, ()-CE-123, a potent, selective, and novel atypical DAT inhibitor, has undergone iterative testing as part of the preclinical evaluation step. This required the process transfer, scale-up, and synthesis of a 1 kg preclinical batch.

Novel Selective and Low-Toxic Inhibitor of CPB2.8ΔCTE (CPB) One Important Cysteine Protease for Virulence.

Leishmaniasis is a highly prevalent, yet neglected disease caused by protozoan parasites of the genus . In the search for newer, safer, and more effective antileishmanial compounds, we herein present a study of the mode of action in addition to a detailed structural and biological characterization of [-benzoyl-'-benzyl-″-(4-tertbutylphenyl)guanidine]. X-ray crystallography and extensive NMR experiments revealed that nearly exclusively adopts the conformation stabilized by an intramolecular hydrogen bond.

Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues.

Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R.

Mass spectrometry study of N-alkylbenzenesulfonamides with potential antagonist activity to potassium channels.

Herein, we report the synthesis and mass spectrometry studies of several N-alkylbenzenesulfonamides structurally related to sulfanilic acid. The compounds were synthesized using a modified Schotten-Baumann reaction coupled with Meisenheimer arylation. Sequential mass spectrometry by negative mode electrospray ionization (ESI(-)-MS/MS) showed the formation of sulfoxylate anion (m/z 65) observed in the mass spectrum of p-chloro-N-alkylbenzenesulfonamides.

Synthesis of potentially bioactive PABA-related N-(aminoalkyl)lactamic amino acids and esters via selective S(N)Ar reactions.

Potentially bioactive N-(aminoalkyl)lactamic amino acids and esters were synthesized in satisfactory to good yields by S(N)Ar reactions of aromatic acids with N-(3-aminopropyl)lactams followed by esterification with tertiary amino alcohols. The addition-elimination S(N)Ar mechanism was confirmed by NMR and MS measurements.

Fabrication, structural characterization, and applications of langmuir and langmuir-blodgett films of a poly(azo)urethane.

The synthesis of a poly(azo)urethane by fixing CO(2) in bis-epoxide followed by a polymerization reaction with an azodiamine is presented. Since isocyanate is not used in the process, it is termed "clean method" and the polymers obtained are named "NIPUs" (non-isocyanate polyurethanes). Langmuir films were formed at the air-water interface and were characterized by surface pressure vs mean molecular area per mer unit (Pi-A) isotherms.