Significance of Povarov Reaction in Organic synthesis: An overview

:The Povarov reaction has enabled and shaped the art and science of organic synthesis over the last few decades to an extent that has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent Pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Povarov cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. Selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of organic synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized

Synthesis, Magnetic Susceptibility, Thermodynamic Study and Bio-Evaluation of Transition Metal Complexes of New Schiff Base Incorporating INH Pharmacophore

Transition metal complexes of synthesized organic ligands incorporating INH were successfully investigated by potentiometrically. The stability constants of these binary complexes were evaluated and order of stability constant found as above Zn(II) > Co(II) > Ni(II) > Mn(II) > Cu(II). Magnetic moment value clearly indicates that newly prepared transition metal complexes of N-[(E)-(2-Hydroxyphenyl)methylen]isonicotinohydrazid are paramagnetic in nature. The stability constants for complexes decrease with an increasing temperature, indicating that the composition equilibrium is exothermic in nature. Also the change in enthalpy (ΔH) and change in Gibb’s free energy (ΔG) were negative for all of the systems which suggested that all of the reactions were exothermic. The change in entropy (ΔS) found positive for most of the complexes which indicate in metal–ligand binding process is entropy favourable. Metal complexes of organic ligand shows moderate antibacterial activity against gram positive and gram negative bacteria. It also possesses prominent antifungal activity for Nickel (II) complex. Biological evaluation results of transition metal complexes show superior pharmacological applications as compared to organic ligand.</p

Synthesis, Magnetic Moment, Antibacterial, and Antifungal Studies of INH Incorporating Schiff Base Metal Complexes

The Isoniazid (INH) ring system is one of the most important heterocycles in nature, as it represents an important structural motif of many biological compounds. It possesses significant antibacterial activity and is given in combination with Rifampicin, ethambutol, or pyrazinamide. There is, therefore, an urgent need to design rapid, efficient, and environmentally benign protocols for the synthesis of metal complexation of INH-based moiety to improve its stability and bioactivity. Herein, we have developed a novel tetradentate INH incorporated Schiff base as an organic ligand, formed by the condensation reaction of INH and 4-hydroxy benzaldehyde in ethanol using glacial acetic acid resulting in the formation of N-[(E)-(4-Hydroxyphenyl)methylen]isonicotinohydrazid as primary ligand and its Cu(II), Co(II), Mn(II), Ni(II) and Zn(II) complexes having general composition [M(L)(H2O)2]·2H2O. Spectroscopic characterization such as mass, IR, UV, 1HNMR, and 13CNMR of N-[(E)-(4-Hydroxyphenyl)methylen]isonicotinohydrazid led to the conclusion that the synthesized Schiff base acts as a tetradentate organic ligand and can be used for further metal complexation. IR’s functional group frequency change confirmed its complex formation with transition metal ions. The octahedral geometry for the [M(INH-L)].2H2O is proposed based on analytical and spectroscopic data of complexes. Magnetic susceptibility study indicates newly prepared transition metal complexes are paramagnetic. Present research work has several advantages such as the eco-friendly method, easy work-up, excellent yield for the preparation of bioactive organic ligands, improved stability, and antibiotic, antifungal properties of organic ligands after complexation.</p

Design, Synthesis of Novel, Potent, Selective, Orally Bioavailable Adenosine A_2A Receptor Antagonists and Their Biological Evaluation

Our initial structure–activity relationship studies on 7-methoxy-4-morpholino-benzothiazole derivatives featured by aryloxy-2-methylpropanamide moieties at the 2-position led to identification of compound <b>25</b> as a potent and selective A_2A adenosine receptor (A_2AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A_2A receptor antagonists bearing substituted 1-methylcyclohexyl-carboxamide groups at position 2 of the benzothiazole scaffold and endowed with better solubility and oral bioavailability. Compounds <b>41</b> and <b>49</b> demonstrated a number of positive attributes with respect to in vitro ADME properties. Both compounds displayed good pharmacokinetic properties with 63% and 61% oral bioavailability, respectively, in rat. Further, compound <b>49</b> displayed oral efficacy in 6-OHDA lesioned rat model of Parkinson diseases