Open Access. Powered by Scholars. Published by Universities.®
Medicinal and Pharmaceutical Chemistry Commons™
Open Access. Powered by Scholars. Published by Universities.®
- Discipline
Articles 1 - 2 of 2
Full-Text Articles in Medicinal and Pharmaceutical Chemistry
Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg
Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg
All Faculty Scholarship for the College of the Sciences
C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph3PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The …
Antitrypanosomal, Antileishmanial, And Antimalarial Activities Of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, A New Class Of Trypanothione Reductase Inhibitor, And Of N-Acyl Derivatives Of 2-Amino-4-Chlorophenyl Phenyl Sulfide, Seheli Parveen, M. O. Faruk Khan, Susan E. Austin, Simon L. Croft, Vanessa Yardley, Peter Rock, Kenneth T. Douglas
Antitrypanosomal, Antileishmanial, And Antimalarial Activities Of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, A New Class Of Trypanothione Reductase Inhibitor, And Of N-Acyl Derivatives Of 2-Amino-4-Chlorophenyl Phenyl Sulfide, Seheli Parveen, M. O. Faruk Khan, Susan E. Austin, Simon L. Croft, Vanessa Yardley, Peter Rock, Kenneth T. Douglas
Pharmaceutical Science and Research
Quaternization of the nitrogen atom of 2-amino-4-chlorophenyl phenyl sulfide analogues of chlorpromazine improved inhibition ∼40-fold (3′,4′-dichlorobenzyl-[5-chloro-2-phenylsulfan- ylphenylamino)-propyl]-dimethylammonium chloride inhibited trypanothione reductase from Trypanosoma cruzi with a linear competitive Ki value of 1.7 ( 0.2 µM). Molecular modelling explained docking orientations and energies by: (i) involvement of the Z-site hydrophobic pocket (roughly bounded by F396′, P398′, and L399′), (ii) ionic interactions for the cationic nitrogen with Glu-466′ or -467′. A series of N-acyl-2-amino-4-chlorophenyl sulfides showed mixed inhibition (Ki, Ki′ ) 11.3-42.8 µM). The quaternized analogues of the 2-chlorophenyl phenylsulfides had strong antitrypanosomal and antileishmanial activity in vitro against T. bruceirhodesiense STIB900, …