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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]