Mhammed Ansar

In the title molecule, C₂₀H₁₈ClN₃O₂, the 2-chlorophenyl group is disordered to a small extent [occupancies 0.875 (2)/0.125 (2)]. The phenylacetamide moiety is nearly planar due to a weak, intramolecular C—H...O hydrogen bond. In the crystal, N—H...O hydrogen bonds and π-stacking interactions between pyridazine and phenyl rings form helical chains of molecules in the b-axis direction, which are linked by C—H...O hydrogen bonds and C—H...π(ring) interactions. A Hirshfeld surface analysis was performed, which showed that H...H, C...H/H...C and O...H/H...O interactions to dominate the intermolecular contacts in the crystal.

The triazole scaffold is a crucial component of heterocyclic chemistry, serving as a basic building block in organic synthesis, materials science, and medicinal chemistry. Triazole is a five-membered ring composed of three nitrogen atoms and two carbon atoms, and it exists in two isomeric forms: 1,2,3-triazole and 1,2,4-triazole. Compounds featuring the triazole ring are important heterocycles known for their diverse biological activities, including antimicrobial, antiproliferative, antimalarial, anticonvulsant, anti-inflammatory, antineoplastic, antiviral, analgesic, and anticancer properties. As a result, triazole derivatives have attracted significant attention from researchers. This review aims to provide a thorough overview of the published studies on the synthesis of triazole derivatives, highlighting various methods for obtaining the triazole moiety. These methods include classical approaches as well as microwave and ultrasound-assisted techniques.

Pyrazole, characterized by a five-membered heterocyclic structure featuring two neighboring nitrogen atoms, serves as a core element. Pyrazoles hold a privileged status as versatile frameworks in various sectors of the chemical industry, including medicine and agriculture. Previous reviews have extensively highlighted the significance of pyrazoles and their diverse biological activities, encompassing roles such as antituberculosis, antimicrobial, antifungal, anti-inflammatory, anticancer, and antidiabetic agents. Consequently, they have garnered substantial interest from researchers. The aim of this review is to offer a comprehensive overview of the published research related to the synthesis of pyrazole derivatives, encompassing a discussion of diverse methods for accessing the pyrazole moiety. These methods span from utilizing transition-metal catalysts and photoredox reactions to employing one-pot multicomponent processes, novel reactants, and innovative reaction types. It encompasses studies conducted by numerous scientists worldwide, showcasing collective efforts in advancing the methodologies and applications of pyrazole derivatives.

The quinoxaline unit in the title molecule, C₁₈H₁₆N₄O₅, is slightly puckered [dihedral angle between the rings = 2.07 (12)°] while the whole molecule adopts an L-shaped conformation. Intramolecular hydrogen bonding determines the orientation of the substituted phenyl ring and the amide nitrogen atom is almost planar. The packing in the crystal is governed by C—H...O hydrogen bonds and slipped π-stacking interactions.

Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein–ligand contact maps were derived from trajectories of simulated protein–ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein–ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor.

In the title molecule, C₁₇H₂₀N₂O₄, the inner part of the ester substituent is nearly perpendicular to the dihydropyridazine ring, forming a dihedral angle of 83.21 (7)°. In the crystal, inversion dimers are formed by pairwise C—H...O interactions with the dimers connected into chains extending along the b-axis direction by C—H...π(ring) interactions. The chains are connected by π-stacking interactions to give corrugated layers parallel to the ab plane. The terminal ethyl group is disordered over two two sets of sites with the major component having a site occupancy factor of 0.715 (10)

The asymmetric unit of the title molecule, C₁₂H₁₂O₃, contains two independent molecules having opposite conformations and each forming self-dimers through complementary O—H...O hydrogen bonds. These dimers are linked by weak C—H...π interactions and C—H...O hydrogen bonds into a three-dimensional structure in which one can discern layers parallel to the bc plane. A Hirshfeld surface analysis of the intermolecular interactions is included.

In the title molecule C₁₇H₁₃NO, the phenyl rings are inclined to one another by 48.04 (9)°. In the crystal, weak C—H...π(ring) interactions form a layered structure parallel to the ab plane.

In the title molecule, C₂₁H₂₄N₂OS, the five-membered ring is planar with an r.m.s. deviation of 0.0142 Å. The phenyl rings are inclined to the plane of the dihydroimidazolone ring by 60.81 (6) and 79.23 (6)°. In the crystal, inversion dimers are formed by a C—H...O hydrogen bond and a C—H...π(ring) interaction. Additional C—H...O hydrogen bonds and C—H...π(ring) interactions connect these dimers into chains along the c-axis direction.

In the title compound, C₁₉H₂₀N₂O₂, the phenyl rings are inclined to the five-membered ring by 58.08 (6) and 66.31 (5)°. In the crystal, pairwise N—H...O and C—H...N hydrogen bonds form chains along the a-axis direction which are connected into layers approximately parallel to [010] by C—H...O hydrogen bonds. The layers are connected by C—H...π(ring) interactions.