Recent advances in transition metal-catalyzed reactions of chloroquinoxalines: Applications in bioorganic chemistry.

The importance of the quinoxaline framework is exemplified by its presence in the well-known drugs such as varenicline, brimonidine, quinacillin, etc. In the past few years, preparation of a variety of organic compounds containing the quinoxaline framework has been reported by several research groups. The chloroquinoxalines were successfully used as substrates in many of these synthetic approaches due to their easy availability along with the reactivity especially towards a diverse range of metal and transition metal-catalyzed transformations including Sonogashira, Suzuki, Heck type of cross-coupling reactions.

Sonochemical synthesis and biological evaluation of isoquinolin-1(2H)-one/isoindolin-1-one derivatives: Discovery of a positive ago-allosteric modulator (PAAM) of 5HTR.

Efforts have been devoted for the discovery and development of positive allosteric modulators (PAMs) of 5-HTR because of their potential advantages over the orthosteric agonist like Lorcaserin that was withdrawn from the market. On the other hand, pursuing a positive ago-allosteric modulator (PAAM) is considered as beneficial particularly when an agonist is not capable of affecting the potency of the endogenous agonist sufficiently. In search of a suitable PAAM of 5-HTR we adopted an in silico based approach that indicated the potential of the 3-(1-hydroxycycloalkyl) substituted isoquinolin-1-one derivatives against the 5-HTR as majority of these molecules interacted with the site other than that of Lorcaserin with superior docking scores.

Ultrasound assisted one-pot synthesis of rosuvastatin based novel azaindole derivatives via coupling-cyclization strategy under Pd/Cu-catalysis: Their evaluation as potential cytotoxic agents.

Addressing the increasing incidences of cancer worldwide along with the multifaceted problem of drug resistance via development of new anticancer agents has become an essential goal. Due to the known cytotoxic effects and reported Akt inhibitory potential of azaindoles we designed a new framework incorporating the structural features of rosuvastatin and 5- or 7-azaindole. The framework was used to construct a library of small molecules for further pharmacological evaluation.

Fe(III)-catalyzed regioselective and faster synthesis of isocoumarins with 3-oxoalkyl moiety at C-4: Identification of new inhibitors of PDE4.

In search of potent and new anti-inflammatory agents, we explored a new class of isocoumarin derivatives possessing the 3-oxoalkyl moiety at C-4 position. These compounds were synthesized via the FeCl catalyzed construction of isocoumarin ring. The methodology involved coupling of 2-alkynyl benzamides with alkyl vinyl ketone and proceeded via a regioselective cyclization to give the desired compound as a result of formation of CO and CC bonds.

Amberlyst-15 catalysed synthesis of novel indole derivatives under ultrasound irradiation: Their evaluation as serotonin 5-HT receptor agonists.

A series of indole based novel Schiff bases was designed as potential agonists of 5-HT receptor that was supported by docking studies in silico. These compounds were synthesized via Amberlyst-15 catalysed condensation of an appropriate pyrazole based primary amine with the corresponding indole-3-aldehyde under ultrasound irradiation at ambient temperature. A number of target Schiff bases were obtained in good yields (77-87%) under mild conditions within 1 h.

Pd-catalysed general access to 7-membered N/O-heterocyclic compounds as potential agents against inflammation.

A Pd-catalysed regioselective synthesis of 4,5-disubstituted 7-membered N/O-heterocycles was achieved the 7- cyclization followed by C-C bond formation of 2-(1-alkynyl)phenylacetamide. The ligand/additive free cascade reaction proceeded in the presence of PdCl in aqueous MeCN when the separate and individual use of methyl vinyl ketone and allyl bromide generally afforded an O- and N-heterocycle, respectively. The pharmacological assay was performed to identify the first example of a 1-benzo[]azepin-2(3)-one based novel inhibitor of PDE4B.

CuCl-catalyzed inexpensive, faster and ligand/additive free synthesis of isoquinolin-1(2H)-one derivatives via the coupling-cyclization strategy: Evaluation of a new class of compounds as potential PDE4 inhibitors.

In spite of possessing a wide range of pharmacological properties the anti-inflammatory activities of isoquinolin-1(2H)-ones were rarely known or explored earlier. PDE4 inhibitors on the other hand in addition to their usefulness in treating inflammatory diseases have been suggested to attenuate the cytokine storm in COVID-19 especially TNF-α. In our effort, a new class of isoquinolin-1(2H)-ones derivatives containing an aminosulfonyl moiety were designed and explored as potential inhibitors of PDE4.

PdCl-catalyzed synthesis of a new class of isocoumarin derivatives containing aminosulfonyl / aminocarboxamide moiety: First identification of a isocoumarin based PDE4 inhibitor.

While anti-inflammatory properties of isocoumarins are known their PDE4 inhibitory potential was not explored previously. In our effort the non-PDE4 inhibitor isocoumarins were transformed into the promising inhibitors via introducing an aminosulfonyl/aminocarboxamide moiety to the C-3 benzene ring attached to the isocoumarin framework. This new class of isocoumarins were synthesized via a PdCl-catalyzed construction of the 4-allyl substituted 3-aryl isocoumarin ring starting from the appropriate 2-alkynyl benzamide derivative.

Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents.

A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were designed and synthesized via the ultrasound assisted Cu-mediated coupling-cyclization in a single pot with remarkable regioselectivity. The phthalides were generally obtained at lower temperature whereas the use of elevated temperature afforded isocoumarins. Two compounds e.

Synthesis of 11,12-dihydro benzo[c]phenanthridines via a Pd-catalyzed unusual construction of isocoumarin ring/FeCl-mediated intramolecular arene-allyl cyclization: First identification of a benzo[c]phenanthridine based PDE4 inhibitor.

In spite of their various pharmacological properties the anti-inflammatory potential of benzo[c]phenanthridines remained underexplored. Thus, for the first time PDE4 inhibitory potential of 11,12-dihydro benzo[c]phenanthridine/benzo[c]phenanthridine was assessed in vitro. Elegant synthesis of these compounds was performed via a multi-step sequence consisting of a Pd-catalyzed unusual construction of 4-allyl isocoumarin ring and FeCl-mediated intramolecular regio- as well as site-selective arene-allyl cyclization as key steps.

Novel isatin-indole derivatives as potential inhibitors of chorismate mutase (CM): their synthesis along with unexpected formation of 2-indolylmethylamino benzoate ester under Pd-Cu catalysis.

A series of novel isatin-indole derivatives has been designed as potential inhibitors of chorismate mutase (CM) that is known to be present in bacteria, fungi and higher plants but not in human. The design was supported by docking studies that predicted strong interactions of these molecules with CM. The target compounds were synthesized the one-pot coupling/cyclization method involving the reaction of an isatin based terminal alkyne with 2-iodosulfanilides under Pd-Cu catalysis.

InCl mediated heteroarylation of indoles and their derivatization via CH activation strategy: Discovery of 2-(1H-indol-3-yl)-quinoxaline derivatives as a new class of PDE4B selective inhibitors for arthritis and/or multiple sclerosis.

A new class of PDE4 inhibitors were designed and synthesized via the InCl mediated heteroarylation of indoles and their further derivatization through the Pd(II)-catalyzed CH activation strategy. This effort allowed us to discover a series of 2-(1H-indol-3-yl)-quinoxaline based inhibitors possessing PDE4B selectivity over PDE4D and PDE4C. One of these compounds i.