Ajay Kumar Srivastava

Synthesis of Alkaloid-Mimicking Tricyclic Skeletons by Diastereo- and Regioselective Ugi/ipso-Cyclization/Aza-Michael Cascade Reaction in One-Pot.

A one-pot process has been developed for preparing alkaloid-like tricyclic skeletons by employing an Ugi reaction, an acid mediated ipso-cyclization and an aza-Michael addition. The transformation is operationally simple and provides products in a diastereo- and regioselective manner with good-to-excellent yields.

Naphthalimide derivatives with therapeutic characteristics: a patent review

Introduction: Naphthalimides are important aromatic heterocycles with immense pharmacological significance as they serve as core scaffold for many antitumor, anti-inflammatory, antidepressant, antiprotozoal and antiviral agents, etc. The tricyclic planar ring system of naphthalimide is primarily responsible for its intercalation with DNA to perturb the cellular events and the substitution pattern of the molecule leads to several other applications. The promising pharmacological activity profile and ease of synthesis have been attractive in design and development of new class of naphthalimides and their conjugates as various potential therapeutic agents. Few of such molecules are currently under preclinical and clinical evaluations. Areas covered: Important patents focusing on naphthalimides as potential class of therapeutics, published between the period of 2006 – 2011have been covered. The reports are presented together with a review of the related structural chemical space. This review mainly focuses on the therapeutic applications, structural modifications of naphthalimide scaffold, their conjugates and heterocyclics bearing naphthalimide moiety. Expert opinion: The tricyclic planar ring system of naphthalimide restrains important pharmaceutical properties along with excellent fluorescent after proper substitution pattern. Linking these active naphthalimide derivatives with other active pharmacophore has become an interesting area of research. The utility of naphthalimide derivatives as novel pharmaceutical and photochemical agents can be further enhanced by introducing polar side chains and fusing functionalized heterocyclic rings with naphthalimide cores.

Efficient Construction of Azaspiro[4.5]trienone Libraries via Tandem Ugi 4CC/Electrophilic ipso-Iodocyclization in One-Pot

A solution-phase parallel synthesis of pharmaceutically important azaspiro[4.5]trienones has been developed by performing tandem Ugi four-component condensation (U4CC), involving substituted p-anisidines, aldehydes, 3-alkyl/aryl-propiolic acids, and isocyanides, and iodine-mediated ipso-iodocyclization in one-pot. This highly atom economical process produced functionalized azaspiro[4.5]trienones in good to excellent overall yields and products were easily isolated by precipitation followed by crystallization. These vinyl-iodide bearing azaspiro[4.5]trienones were utilized for further modifications through Suzuki coupling and deiodination reaction to demonstrate the suitability of these products for various palladium catalyzed modifications. The present method provides an easy access to highly functionalized azaspiro[4.5]trienones that can be useful in drug discovery research.

Development of constrained tamoxifen mimics and their antiproliferative properties against breast cancer cells

An efficient synthesis of a new series of tamoxifen mimics is described by employing iodine catalyzed ipsocyclization strategy followed by Suzuki coupling. A molecular docking studies of the synthesized compounds 11a-n and 12 in estrogen receptor (ER-α) showed that the scaffolds are fitting well in the groove, thereby suggesting them as promising antiproliferative agents for estrogen dependent breast cancer lines. All compounds were tested in vitro against breast cancer cell lines-ER positive, MCF-7; ER negative, MDA-MB-231; and control mammary epithelial cells, MEpiC. The biological results showed that most of the compounds are active against MCF-7 with IC50 values less than 6.5μM which corroborate the results of molecular docking studies.

Tankyrase Inhibitors as Therapeutic Targets for Cancer

Tankyrase 1 and 2 belonging to the family of poly(ADP-ribosyl)ases play an important role in PARsylation by utilizing NAD+ as a substrate in order to generate ADP-ribose polymers. Tankyrases are involved in a number of cellular functions, that includes telomere homeostasis, mitotic spindle formation, vesicle transport linked to glucose metabolism, Wnt/β-catenin signalling, and viral replication. These roles of tankyrases in disease-relevant cellular processes have made them attractive drug targets. Recently, several inhibitors have been identified as potential clinical leads. The current review covers the progress, mechanism and binding modes of recently known Tankyrase inhibitors and discusses the rational approaches that were used to identify the tankyrase inhibitors.

An Efficient One-Pot Synthesis of Densely Functionalized Fused-Quinolines via Sequential Ugi4CC and Acid-Mediated Povarov-Type Reaction

A divergent synthesis of fused-quinolines has been explored by performing Ugi four-component condensation and sulfuric acid promoted deprotection/Povarov-type reaction in one-pot. The process involves Ugi condensation of propiolic acids, aldehydes/ketones, aminoaldehyde acetals and isocyanides followed by sulfuric acid promoted deprotection and Povarov-type reaction with anilines in ethanol. This method enables straightforward access to the structurally diverse 2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones (DHPQ), 3,4-dihydrobenzo[b][1,6]naphthyridin-1(2H)-ones (DHBN), and 2,3,4,5-tetrahydro-1H-azepino[4,3-b]quinolin-1-ones (THAQ), starting from readily available starting materials.