Enantioselective LC analysis and determination of selective serotonin reuptake inhibitors

LC separation of biologically and pharmaceutically important enantiomers (from racemic or non-racemic mixtures) remains a subject of importance. The present review article deals with the liquid chromatographic enantioseparation of chiral selective serotonin reuptake inhibitors (SSRIs), namely citalopram, paroxetine, sertraline and fluoxetine. It is now known that the enantiomers of numerous psychotropic drugs exhibit distinct pharmacodynamics, pharmacokinetic patterns and receptor binding properties, and psychiatric patients are frequently taking more than one medication. Therefore, monitoring of the levels of these analytes in biological fluids is important to determine the levels of enantiomer concentrations; the present paper may be helpful in understanding the present state of available methods (along with a critical discussion of applicability of the methods) and in developing the new ones for this purpose. Different approaches using LC discussed herein may be applied for determining the enantiomeric composition (and enantiomeric purity) of SSRIs and numerous other racemic drugs, of current/future pharmaceutical importance and utility, using simple separation methods, instrumentation, inexpensive reagents and potentially significant analytical approaches. The contents cover the essential data to understand the various separation techniques and associated issues, if any, with documented examples.     

Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay

Journal of Computer-Aided Molecular Design - The c-Jun N-terminal kinase 3 (JNK3) signaling cascade is activated during cerebral ischemia leading to neuronal damage. The present study was carried...     

Enantiomeric Separation of New Chiral Azole Compounds

Twelve new azole compounds were synthesized through an ene reaction involving methylidene heterocycles and phenylmaleimide, producing four oxazoles, five thiazoles, and one pyridine derivative, and ethyl glyoxylate for an oxazole and a thiazole compound. The twelve azoles have a stereogenic center in their structure. Hence, a method to separate the enantiomeric pairs, must be provided if any further study of chemical and pharmacological importance of these compounds is to be accomplished. Six chiral stationary phases were assayed: four were based on macrocyclic glycopeptide selectors and two on linear carbohydrates, i.e., derivatized maltodextrin and amylose. The enantiomers of the entire set of new chiral azole compounds were separated using three different mobile phase elution modes: normal phase, polar organic, and reversed phase. The most effective chiral stationary phase was the MaltoShell column, which was able to separate ten of the twelve compounds in one elution mode or another. Structural similarities in the newly synthesized oxazoles provided some insights into possible chiral recognition mechanisms.     

Common fixed points of two multivalued nonexpansive mappings by one-step iterative scheme

In this paper, we introduce a new one-step iterative process to approximate common fixed points of two multivalued nonexpansive mappings in a real uniformly convex Banach space. We establish weak and strong convergence theorems for the proposed process under some basic boundary conditions.     

Cobalt (II) and Copper (I) Complexes of Rigid Bidentate [N‐(2, 6‐Diisopropyl‐phenyl)imino]acenapthenone Ligand: Synthesis and Structural Studies

The cobalt(II) complex [CoCl₂(2, 6‐iPrC₆H₃‐BIAO)]₂ ( 1 ) of rigid unsymmetrical imine, carbonyl mixed ligand [N‐(2, 6‐diisopropylphenyl)‐imino]acenapthenone] (2, 6‐iPrC₆H₃‐BIAO) ( L1 ) can be achieved by the reaction of CoCl₂ and neutral [N‐(2, 6‐diisopropylphenyl)‐imino]acenapthenone] ligand. When ligand L1 reacted with CuCl in dichloromethane solution, only nitrogen coordinated copper complex [CuCl(2, 6‐iPrC₆H₃‐BIAO)] ( 2 ) was obtained. In the solid‐state structure, compound 1 is dimeric through the chelating two μ₂ chlorine atoms and each cobalt atom adopts either a distorted trigonal bipyramidal or a distorted square pyramidal arrangement. In contrast, the molecular structure of compound 2 reveals that copper is coordinated by imino nitrogen and adopts a linear arrangement around the central metal atom. The crystal structure of the rigid bidentate mixed nitrogen and oxygen ligand (2, 6‐iPrC₆H₃‐BIAO) ( L1 ) is also reported.     

Accidental discovery of a ‘longer-range’ vinylogous Pummerer-type lactonization: formation of sulindac sulfide lactone from sulindac

Unexpected formation of sulindac sulfide lactone occurred when sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous sulindac sulfide and indomethacin did not undergo such lactonization under similar reaction conditions. We believe that the sulfoxide function in sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.     

Synthesis,Spectral Characterization,and Antimicrobial Evaluation of N,N′-(1,4-Phenylene)diurea Derivatives

Russian Journal of Organic Chemistry - A series of new 1,1′-(1,4-phenylene)diurea derivatives were synthesized by reacting 1,4-diiso­cyanato­benzene with various biologically...