Pravin Patil

A comprehensive review on synthesis and designing aspects of coumarin derivatives as monoamine oxidase inhibitors for depression and Alzheimer's disease.

Monoamine oxidase (MAO) enzyme inhibition is a crucial target for the management of depression and Alzheimer disease and inhibitors of MAO are the most important drugs for their management. Coumarins are a large family of compounds, of natural and synthetic origin, that exhibit a variety of pharmacological activities, including MAO inhibition. The current review highlights the design and synthetic methods of coumarin derivatives as well as coumarins obtained from plant source as MAO inhibitors for treatment of depression and Alzheimer disease with salient finding related to structure-activity relationship. The aim of present review is to find out natural as well as synthetic coumarins as MAO inhibitors.

Three-component strategy toward 5-membered heterocycles from isocyanide dibromides

A three-component strategy starting from isocyanides allows a straightforward synthesis of five-membered ring heterocycles. New cascades were developed involving the addition of a nitrogenated nucleophile-an azide or a tetrazole-on isocyanide dibromides, an electrocyclization, and a Suzuki coupling, which afford new accesses to tetrazole and triazole scaffolds.

Graphene oxide based magnetic nanocomposites for efficient treatment of breast cancer

The present work reports a simple one step synthesis of nanoscale graphene oxide magnetic composites (GO-IO) using ferrofluid (GO-IOF). The obtained GO-IO were compared with GO-IO obtained from in situ (GO-IOI) methods. Anastrozole (ANS) was loaded on the GO-IOI and GO-IOF via simple stirring method to form GO-IOA and GO-IOFA respectively. These GO-IO prepared by two techniques were characterized using spectroscopic techniques and vibrating sample magnetometer (VSM) analysis. Particle size and potential were measured using Malvern Zetasizer. Scanning electron microscopy (SEM) was used for studying the surface morphology of GO-IO, and in addition to this elemental analysis was also performed for confirming the presence of iron. The cell viability assay was carried out using the MCF-7 cell line. It revealed that GO-IOFA had reasonably high cytotoxicity (49.7%) compared to GO (13.1%), ANS (16.6), GO-IOI (13%), GO-IOF (13.6) and GO-IOIA (18.34%). Both, GO-IOIA and GO-IOFA showed improved cytotoxicity when compared with pure ANS. GO-IOF were found to exhibit superior magnetic activity due to higher iron content along with smaller particle size and higher loading efficiency compared to GO-IOI. The overall effect suggests that GO-IO can be utilized as efficient carriers for the loading of chemotherapeutic agents.

MCR synthesis of a tetracyclic tetrazole scaffold

Scaffold diversity is key in the ongoing exercise of discovery of novel bioactive compounds using high throughput screening (HTS). Based on the Ugi tetrazole synthesis we have designed novel bi- and tri-cyclic scaffolds featuring interesting pharmacophore properties. The compounds of the scaffold (B) are synthesizable in large diversity and numbers in two steps using (hetero)phenylethylamines, HN3, oxo components and iscyanoacetaldehyde(dimethylacetale). The chemistry is amenable to parallel synthesis and is used to enhance and fill the screening decks of the European Lead factory (ELF). Here, we are reporting full experimental details, scope and limitations of the reaction, cheminformatic analysis and the 3D structures of selected compounds.

Ugi-Smiles couplings of 4-substituted pyridine derivatives: a fast access to chloroquine analogues

4-Hydroxy and mercapto pyridines were successfully tested in Ugi-Smiles couplings. Such multicomponent reactions applied to quinoline derivatives afford a very convenient and short synthesis of antimalarial analogues.

Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach

Present invention relates to design of nanostructured lipid carriers (NLC) to augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer 188 as a surfactant and tween 80 as a co-surfactant using high pressure homogenizer by 23 factorial design approach. Formed CAR-NLCs were assessed for various performance parameters. Accelerated stability studies demonstrated negligible change in particle size and entrapment efficiency, after storage at specified time up to 3 months. The promising findings in this investigation suggest the practicability of these systems for enhancement of bioavailability of drugs like CAR.

A universal isocyanide for diverse heterocycle syntheses.

Novel scaffolds are of uttermost importance for the discovery of functional material. Three different heterocyclic scaffolds easily accessible from isocyanoacetaldehyde dimethylacetal 1 by multicomponent reaction (MCR) are described. They can be efficiently synthesized by a Ugi tetrazole multicomponent reaction of 1. We discuss the synthesis, 3D structures, and other physicochemical properties.

Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent ☆

A series of novel 1,3-dioxane-2-carboxylic acid derivatives containing alkyl chain tether and substituted phenyl group as a lipophilic tail have been prepared as agonists of PPARalpha and gamma. c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid 13c exhibited potent hypoglycemic and lipid lowering activity with high oral bioavailability in animal models.

De Novo Assembly of Highly Substituted Morpholines and Piperazines

The morpholine and piperazine with their remarkable physical and biochemical properties are popular heterocycles in organic and medicinal chemistry used in rational property design. However, in the majority of cases these rings are added to an existing molecule in a building block approach thus limiting their substitution pattern and diversity. Here we introduce a versatile de novo synthesis of the morpholine and piperazine rings using multicomponent reaction chemistry. The large scale amenable building blocks can be further substituted at up to four positions, making this a very versatile scaffold synthesis strategy. Our methods thus fulfill the increasing demand for novel building block design and nontraditional scaffolds which previously were not accessible

Modulation of PPAR receptor subtype selectivity of the ligands: aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety.

Oxazole containing glycine and oximinobutyric acid derivatives were synthesized as PPARalpha agonists by incorporating polymethylene spacer as a replacement of commonly used phenylene group that connects the acidic head with lipophilic tail. Compound 13a was found to be a selective and potent PPARalpha agonist. Further 1,3-dioxane-2-carboxylic acid derivative 20 was synthesized by replacing the tetramethylene spacer of NS-220, a selective PPARalpha agonist with phenylene group and found to exhibit PPARalpha/gamma dual agonism. These results suggest that compounds possessing polymethylene spacer between pharmacophore and lipophilic tail exhibit predominantly PPARalpha agonism whereas those with an aromatic phenylene spacer shows PPARalpha/gamma dual agonism.