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The asymmetric unit of the title compound, C18H16F2N2·H2O, contains two independent molecules (A and B), and two independent water molecules of crystallization. In molecule A, the imidazole ring makes dihedral angles of 47.46 (7) and 60.98 (6)° with the 2,4-difluorophenyl and methylphenyl rings, respectively. The corresponding angles in molecule B are 45.85 (7) and 62.78 (7)°, respectively. The dihedral angle between the two benzene rings is 64.98 (7)° in molecule A and 65.53 (7)° in molecule B. In the crystal, the two independent molecules are linked by O—H...N and O—H...O hydrogen bonds, forming chains propagating along [100]. These chains are linked via C—H...F hydrogen bonds, forming slab-like two-dimensional networks lying parallel to (001).

Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol) than the parent compound, noscapine (-5.505 kCal/mol) and its existing derivatives (-5.563 to -6.412 kCal/mol). Free energy (ΔG bind ) calculations based on the linear interaction energy (LIE) empirical equation utilizing Surface Generalized Born (SGB) continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol). Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol). The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl) noscapine (6f) binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM), which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM) and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM). All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

An efficient Rh(III)‐catalyzed C−H functionalization of 3‐aryl‐2H‐benzo[e][1,2,4]thiadiazine‐1,1‐dioxides with diaryl and dialkyl alkynes has been developed for the first time to the synthesis of 1‐aminoisoquinoline derivatives in a single step. This method involves through the formation of one C−C bond and one C−N bond followed by desulfonylation to generate a novel series of isoquinolines in good to excellent yields. This is a direct method to produce pharmaceutically more relevant scaffolds with a high functional diversity. [ABSTRACT FROM AUTHOR]

New cocrystals and a salt–cocrystal intermediate system involving the antifungal drug flucytosine (FCY) and various coformers including caffeic acid (CAF), 2‐chloro‐4‐nitrobenzoic acid (CNB), hydroquinone (HQN), resorcinol (RES) and catechol (CAL), are reported. The crystal structures of the prepared multicomponent systems were determined through SC‐XRD analysis and characterized by different solid‐state techniques. All FCY multicomponent systems crystallize in anhydrous form with different stoichiometric ratios. The cocrystals FCY–HQN, FCY–RES and FCY–CAL crystallize in 2:0.5, 2:0.5 and 3:2 stoichiometric ratios respectively. In contrast, FCY–CAF and FCY–CNB crystallize in a 1:1 stoichiometric ratio. The FCY–CAF cocrystal is formed via an acid–pyrimidine heterosynthon. Due to the partial proton transfer from the acid group of CNB to FCY, a three‐point homosynthon is observed between two FCY molecules and the molecules interact via an N—H...O hydrogen bond between FCY and CNB. In FCY phenolic cocrystals, a single‐point O—H...O hydrogen bond is observed. The formation of cocrystals and salt–cocrystal intermediate was further confirmed by difference Fourier map analysis and bond angle differences. Except for FCY–CAL, all the multicomponent systems were reproduced in the bulk scale for further characterization. A detailed Crystal Structural Database search was carried out on the multicomponent systems of FCY with acid coformers and we evaluated the formation of cocrystals/salt based on the ΔpKa values, the difference in the bond distances and bond angles. Additionally, the prepared multicomponent systems exhibited hydration stability for one month under accelerated conditions [40 (2) °C and relative humidity 90–95 (5)%]. [ABSTRACT FROM AUTHOR]

A new and effective method for making bridged bicyclic benzoxepine derivatives were devised through the intermolecular [3+3]‐annulation of benzoxepine‐3‐carboxylates with aminocrotonates in the presence of La(OTf)3. The compounds were formed through reactions involving the benzoxepine moiety's C‐3 and C‐5 carbons to produce C−C and C−N bonds. One of the compound structure (±) 12‐ethyl‐6‐methyl‐3‐hydroxy‐5‐methyl‐2,3,4,7‐tetrahydro‐3,7‐methano benzo[h][1,4]‐oxazonine‐6,12‐dicarboxylate was confirmed by single crystal X‐ray analysis. [ABSTRACT FROM AUTHOR]

Enzalutamide (Enz), sold under the brand name "XTANDI", belongs to a group of drugs known as androgen receptor inhibitors and functions by suppressing androgen's actions, which in turn helps in treating castrate-resistant prostate cancer. The current study focuses on the solvates and cocrystals of enzalutamide. Firstly, we obtained single crystals of 1,4-dioxane (Dox) solvate in two different stoichiometric ratios, Enz–Dox 1 : 0.5 and Enz–Dox 2 : 0.5. Based on this, we chose the coformer pyrazine (Pyrz), which is structurally similar to the Dox solvate. Crystallization of Pyrz with Enz also yielded 1 : 0.5 and 2 : 0.5 stoichiometries like the Dox solvate, but these existed as cocrystals (Enz–Pyrz 1 : 0.5 and Enz–Pyrz 2 : 0.5). Despite the solvate and cocrystal of the same stoichiometry (1 : 0.5/2 : 0.5) exhibiting identical sorts of interactions, the inclusion of a coformer in the cocrystal prompted a few additional bonds to form, but the overall crystal environment is still preserved. From the packing similarity analysis, it was found that Enz–Dox 1 : 0.5 and Enz–Pyrz 1 : 0.5 have similar packing indexes; however, the former generates a 2D hydrogen bonded network and the latter leads to a 3D network. The same trend is observed in the cases of Enz–Dox 2 : 0.5 and Enz–Pyrz 2 : 0.5. Hirshfeld analysis was performed to evaluate the prominence of various intermolecular interactions. Void map analysis enabled us to understand the roles of solvent and coformer in the crystal packing. Periodic DFT computations and DSC studies were performed to correlate thermal stabilities of solvates and cocrystals. Accelerated stability experiments revealed the better stability of cocrystals over solvates. This study provides valuable insights into solvate formation, which can be used as an effective strategy for attaining cocrystals with desired entities. [ABSTRACT FROM AUTHOR]

A green and efficient process for the synthesis of cenobamate has been accomplished in 70% yield and >99% ee through the bio‐reduction of β‐ketotetrazole using Daucus carota whole plant cells. The corresponding β‐hydroxytetrazole was isolated in 60% yield and >98% ee. This is the first report on the biocatalytic reduction of β‐ketotetrazole using plant enzymes derived from D. carota root cells with excellent enantioselectivity. [ABSTRACT FROM AUTHOR]

A novel method has been developed for the synthesis of fused dihydroisoquinoline frameworks through a Rh(III)‐catalyzed annulation of 3‐aryl‐2H‐benzo[e][1,2,4]thiadiazine‐1,1‐dioxides with vinylene carbonates by C−H bond activation. This is the first report on the oxidative C−H functionalization of aryl‐2H‐benzo[e][1,2,4]thiadiazine‐1,1‐dioxide with vinylene carbonate to afford angularly fused heterocycles in good yields with high functional group tolerance. In this approach, vinylene carbonate acts as a glycolaldehyde surrogate to construct the fused dihydroisoquinoline ring systems. [ABSTRACT FROM AUTHOR]

A Selectfluor mediated regioselective π‐extended [3+1+1] annulation using imidazopyridines, acetophenones and DMF as carbon source has been realized. The current route compared to traditional π‐extended annulation reaction utilizes commercially available acetophenones as a cyclic partner and offers three C−C bond formations. This reaction displayed good functional group tolerance wherein DMF served as a carbon synthon. Five‐membered bridged chroman‐4‐one derivative of imidazopyridine has been achieved with 2‐hydroxy acetophenone, wherein DMF acted as a dual carbon synthon and offered four C−C and one C−O bond formation in one‐pot. [ABSTRACT FROM AUTHOR]

The energetics in the Bay of Bengal (BoB) region is influenced by primary and secondary mesoscale ocean processes, such as boundary currents, gyres, and eddies. Using the turbulent kinetic energy budget equation, the fluxes and their role in BoB dynamics are studied. A regional domain with a horizontal resolution of 0.1 ∘ is considered in the Indian Ocean, which includes the BoB region. The analysis of flow energetics reveals differences in eddy kinetic energy (K), shear production flux (P), buoyancy flux (B), and viscous dissipation (ε) terms. Our results reveal the presence of an inverse energy-cascade mechanism in the southern Bay of Bengal, wherein energy flows back into mean flow structures from the turbulent eddies. Further analysis shows that buoyancy flux, B, is the major source of turbulence production in the north and central BoB regions. These results define the mechanisms by which energy is produced and transferred in different regions in the Bay of Bengal. [ABSTRACT FROM AUTHOR]

In this study, a regional modelling approach is adopted using the Modular Ocean Model version 5 (MOM5) with implementation of open boundary condition (OBC) in the Bay of Bengal (BoB) region. The domain is given an initial stratification profile of climatological temperature and salinity and is forced using seasonally varying wind and air-sea fluxes at the surface. A sensitivity analysis is performed by changing the vertical mixing schemes. Changes in vertical mixing schemes have significant impact on the ocean system, including the surface properties. Two different vertical mixing models are used: K-profile parameterization (KPP), and k- ∈ turbulence model. Inter-comparison between these two experiments suggests that k- ∈ model performs seemingly better than the KPP model. With k- ∈ mixing scheme, the simulated sea surface temperature (SST) and mixed layer depth (MLD) are closer to observations. Model generated turbulent kinetic energy (k) and dissipation ( ∈) are different in the two experiments because of different representations of k and ∈ in the two models. The results show the importance of regional modelling and the use of different mixing schemes. Employing a physics-based vertical mixing scheme, such as the k- ∈ turbulence model, shows improvement in the model physics and the model simulated ocean parameters. [ABSTRACT FROM AUTHOR]

Nilutamide (Nil), commercialized under the trade names Nilandron and Anandron, is a nonsteroidal antiandrogen drug used in prostate cancer treatment. The attempts to cocrystallize nilutamide with adenine (Adn) and orotic acid monohydrate (OMH) resulted in the formation of four novel solid forms of the drug, namely the [Nil + Adn] (1 : 1) cocrystal, two new polymorphs of Nil (forms IV and V), and the Nil hydrate ([Nil·H2O] (2 : 0.57)). The crystal structures of the solid forms were elucidated by single-crystal X-ray diffraction. New nilutamide polymorphic forms IV and V were found to contain multiple symmetry-independent molecules in the asymmetric unit whose Z′ = 3 (form IV) and Z′ = 2 (form V), while the three previously reported forms (form I, form II, form III) had Z′ = 1. Despite several attempts, the bulk phase-pure materials of form IV, form V, and [Nil·H2O] (2 : 0.57) could not be attained due to the concomitant crystallization of the solid forms and the poor reproducibility of the crystallization trials. Hence, only limited characterization studies were performed on these phases. In this work, structural elucidation, Hirshfeld, and conformational analysis were explored to understand the similarities and dissimilarities in the crystal packing environment for all the crystal structures. Thermal analysis reveals the phase transformation of [Nil·H2O] (2 : 0.57) to form II. Crystal structure analysis paved the way to understand the prominence of various intermolecular interactions along with the amide dimer and catemer formation. For the [Nil + Adn] (1 : 1) cocrystal, the thermodynamic solubility was evaluated using eutectic concentrations of the components and found to be higher than that of the parent Nil. The effect of hydroxypropyl methylcellulose on the dissolution behavior of the cocrystal was explored. [ABSTRACT FROM AUTHOR]

In this work, we report results from three-dimensional numerical simulations of convection in a rotating cylindrical annulus with mean temperature gradients present along the radial and vertical directions. The simulations have been performed in OpenFOAM (Open-source Field Operation And Manipulation). The bi-directional temperature gradient is achieved by imposing uniform heat flux in a thin circular strip at the outer periphery of the bottom surface, and a uniform temperature at the entire inner cylindrical surface. The study has been carried out for a particular Rayleigh number, Ra = 4.76 × 10 8 , and a range of Taylor numbers, Ta = 6.5 × 10 8 – 2.7 × 10 9 . The Ra value is chosen so that some qualitative comparison could be done with available experimental data. A laminar flow solver has been used to perform the computations in a rotating frame of reference. Complex empirical orthogonal function analysis has been carried out for the velocity and temperature fields. The contour maps of the radial velocity field in the r − θ plane clearly show the existence of mode 4 and 4 AV (amplitude vacillation) baroclinic waves at low values of Ta, which break down into eddies as Ta increases. The mean temperature field in the r–z plane supports the existence of Convective Columnar Plumes (CCP) on the outer edge, which interacts with the baroclinic waves, aiding in the transport of heat in the system. The fluctuations in CCP disintegrate into smaller-scale structures at the highest Ta. Quantification of turbulent fluxes shows the effectiveness of the heat transport at T a ∼ O (10 8) , as compared to T a ∼ O (10 9). Our results clearly demonstrate the role of waves, plumes, and eddies on heat transport in the presence of bi-directional temperature gradients. [ABSTRACT FROM AUTHOR]