One-pot synthesis of tetrahydropyrimidinecarboxamides enabling anticancer activity: a combinative study with clinically relevant brain-penetrant drugs.

In this study, we describe a one-pot three-component synthesis of bioactive tetrahydopyrimidinecarboxamide derivatives employing lanthanum triflate as a catalyst. Out of the synthesized compounds, 4f had the most potent anti-cancer activity and impeded cell cycle progression effectively. Anti-cancer bioactivity was observed in 4f against liver, breast, and lung cancers as well as primary patient-derived glioblastoma cell lines.

Alkoxy-functionalised dihydropyrimido[4,5-]quinolinones enabling anti-proliferative and anti-invasive agents.

In this communication, we explored the synthesis of novel alkoxy-functionalised dihydropyrimido[4,5-]quinolinones using a microwave-assisted multicomponent reaction. All the synthesized molecules were screened for anti-proliferative and anti-invasive activity against glioblastoma cells. 5c shows the most potent anti-proliferative activity with a half maximal effective concentration of less than 3 μM against primary patient-derived glioblastoma cells.

Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities.

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature.

A green bio-organic catalyst (taurine) promoted one-pot synthesis of (/)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches.

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of (/)-2-thioxo-DHPM-5-carboxanilides the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of (/)-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques.

Indole clubbed 2,4-thiazolidinedione linked 1,2,3-triazole as a potent antimalarial and antibacterial agent against drug-resistant strain and molecular modeling studies.

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains.

An efficient, catalyst-free and aqueous ethanol-mediated synthesis of 5-((2-aminothiazol-5-yl)(phenyl)methyl)-6-hydroxypyrimidine-2,4(1,3)-dione derivatives and their antioxidant activity.

In this study, we effectively developed a catalyst-free multicomponent synthesis of 5-((2-aminothiazol-5-yl)(phenyl)methyl)-6-hydroxypyrimidine-2,4(1,3)-dione derivatives employing 2-aminothiazole, ','-dimethyl barbituric acid/barbituric acid and different aldehydes at 80 °C in an aqueous ethanol medium (1 : 1) using group-assisted purification (GAP) chemistry. The essential characteristics of this methodology include superior green credential parameters, metal-free multicomponent synthesis, faster reaction times, greater product yields, simple product purification without column chromatography and higher product yields. All of the synthesized compounds were analyzed against the HepG2 cell line.

Importance of Hybrid Catalysts toward the Synthesis of 5-Pyrano[2,3-]pyrimidine-2-ones/2,4-diones (Thiones).

The pyranopyrimidine core is a key precursor for medicinal and pharmaceutical industries due to its broader synthetic applications as well as its bioavailability. Among its four possible isomers, we found that 5-pyrano[2,3-]pyrimidine scaffolds have a wide range of applicability, and in recent years, they have been intensively investigated, but the development of the main core is found to be more challenging due to its structural existence. In this review article, we cover all of the synthetic pathways that are employed for the development of substituted 4-aryl-octahydropyrano/hexahydrofuro[2,3-]pyrimidin-2-one (thiones) and 5-aryl-substituted pyrano[2,3-]pyrimidindione (2-thiones) derivatives through a one-pot multicomponent reaction using diversified hybrid catalysts such as organocatalysts, metal catalysts, ionic liquid catalysts, nanocatalysts, green solvents, catalyst-/solvent-free conditions, and miscellaneous catalysts as well as the mechanism and recyclability of the catalysts.

Catalyst-Free, Room-Temperature Accessible Regioselective Synthesis of Spiroquinolines and Their Antioxidant Study.

An efficient, regioselective, and environmentally benign approach was established using the multicomponent reaction-based synthesis of novel antioxidant spiroquinoline derivatives such as spiro[dioxolo[4,5-]quinoline], spiro[dioxino[2,3-]quinoline], and spiro[pyrazolo[4,3-]quinoline] by reaction of aryl aldehyde, Meldrum's acid, and amine derivatives under an additive-free reaction in aqueous ethanol. Here, two asymmetric carbon centers, three new C-C bonds, and one C-N bond are developed in the final motif. This synthetic methodology offers excellent yields with an easy workup procedure, high diastereoselectivity [d.

Microwave-assisted multicomponent synthesis of antiproliferative 2,4-dimethoxy-tetrahydropyrimido[4,5-]quinolin-6(7)-ones.

In this study, we demonstrate a simple, highly efficient, rapid and convenient series of 2,4-dimethoxy-tetrahydropyrimido[4,5-]quinolin-6(7)-ones 4a-v. Microwave irradiation facilitates the one-pot multicomponent reaction of different aromatic aldehydes, 6-amino-2,4-dimethoxypyrimidine and dimedone using glacial acetic acid. Metal-free multicomponent synthesis, shorter reaction time, higher product yield, easy product purification without column chromatography and outstanding green credential parameters are the key features of this protocol.

Versatile Synthetic Platform for 1,2,3-Triazole Chemistry.

1,2,3-Triazole scaffolds are not obtained in nature, but they are still intensely investigated by synthetic chemists in various fields due to their excellent properties and green synthetic routes. This review will provide a library of all synthetic routes used in the past 21 years to synthesize 1,2,3-triazoles and their derivatives using various metal catalysts (such as Cu, Ni, Ru, Ir, Rh, Pd, Au, Ag, Zn, and Sm), organocatalysts, metal-free as well as solvent- and catalyst-free neat syntheses, along with their mechanistic cycles, recyclability studies, solvent systems, and reaction condition effects on regioselectivity. Constant developments indicate that 1,2,3-triazoles will help lead to future organic synthesis and are useful for creating molecular libraries of various functionalized 1,2,3-triazoles.

Synthesis of -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles enabling PKBβ/AKT2 inhibitory and anti-glioma activity.

A series of -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound exhibiting promising glioma growth inhibitory properties. Compound was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ.

One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity.

We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study.

Synthesis, crystal structure and studies of novel 2,4-dimethoxy-tetrahydropyrimido[4,5-]quinolin-6(7)-ones.

Herein, acetic acid mediated multicomponent synthesis of novel 2,4-dimethoxy-tetrahydropyrimido[4,5-]quinolin-6(7)-one (2,4-dimethoxy-THPQs) was reported. Single-crystal XRD analysis of four newly developed crystals of 2,4-dimethoxy-THPQs and their DFT study were also reported. The structure of all molecules was optimized using DFT B3LYP/6-31G(d) level and compared with the corresponding single-crystal XRD data.

Syrbactin-class dual constitutive- and immuno-proteasome inhibitor TIR-199 impedes myeloma-mediated bone degeneration in vivo.

Proteasome-addicted neoplastic malignancies present a considerable refractory and relapsed phenotype with patients exhibiting drug resistance and high mortality rates. To counter this global problem, novel proteasome-based therapies are being developed. In the current study, we extensively characterize TIR-199, a syrbactin-class proteasome inhibitor derived from a plant virulence factor of bacterium Pseudomonas syringae pv syringae.

Synthesis and in vitro study of antiproliferative benzyloxy dihydropyrimidinones.

In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1-1.5 h, with 74-97% yield.

Pyridine-2-carboxylic acid as an effectual catalyst for rapid multi-component synthesis of pyrazolo[3,4-]quinolinones.

Green synthesis of pyrazolo[3,4-]quinolinones was designed using bioproduct pyridine-2-carboxylic acid (P2CA) as a green and efficient catalyst. The multi-component reaction of aldehydes, 1,3-cyclodiones and 5-amino-1-phenyl-pyrazoles regioselectively produced pyrazolo[3,4-]quinolinones in excellent yield (84-98%). Recyclization of the catalyst was also investigated.

A novel substrate directed multicomponent reaction for the syntheses of tetrahydro-spiro[pyrazolo[4,3-]quinoline]-8,5'-pyrimidines and tetrahydro-pyrazolo[4,3-]pyrimido[4,5-]quinolines selective multiple C-C bond formation under metal-free conditions.

A versatile and substrate oriented multicomponent reaction for the syntheses of novel highly diastereoselective tetrahydro-1'-spiro[pyrazolo[4,3-]quinoline-8,5'-pyrimidine]-2',4',6'(3')-triones (d.r. up to 20 : 1 ( : )) and tetrahydro-8-pyrazolo[4,3-]pyrimido[4,5-]quinoline-8,10(9)-diones formation of selective multiple C-C bonds under identical reaction conditions ( ethanol as a reaction medium and deep eutectic mixture as a catalyst) is demonstrated.

Impact of an aryl bulky group on a one-pot reaction of aldehyde with malononitrile and -substituted 2-cyanoacetamide.

In this study, we successfully explored the effect of steric hindrance on the one-pot reaction of different aryl aldehydes with malononitrile and -substituted 2-cyanoacetamide in the presence of piperidinium acetate as the catalyst. It involved the Knoevenagel condensation of the aldehyde and malononitrile to produce arylidene malononitrile as an intermediate, which was further treated with -substituted 2-cyanoacetamide to give 6-amino-2-pyridone-3,5-dicarbonitrile derivatives when the less steric bulky group was involved. High steric hindrance changed the earlier reaction route and gave -substituted 2-cyanoacrylamides a slower route.

Hydroxyl alkyl ammonium ionic liquid assisted green and one-pot regioselective access to functionalized pyrazolodihydropyridine core and their pharmacological evaluation.

Herein our team explored a promising synthetic trail to Functionalized pyrazolodihydropyridine core using hydroxyl alkyl ammonium ionic liquid via one-pot fusion of 3-methyl-1-phenyl-1H-pyrazole-5-amine, different heterocyclic aldehydes and 1, 3-Cyclic diones. The aimed compounds were obtained by Domino-Knoevenagel condensation and Michael addition followed by cyclization. The reaction transformation involves the formation of two CC and one CN bond formation.