Study on Typical Diarylurea Drugs or Derivatives in Cocrystallizing with Strong H-Bond Acceptor DMSO

Abstract

Diarylureas are widely used in self-assembly and supramolecular chemistry owing to their outstanding characteristics as both H-bond donors and acceptors. Unfortunately, this bonding property is rarely applied in the development of urea-containing drugs. Herein, seven related dimethyl sulfoxide (DMSO) complexes were screened from 12 substrates involving sorafenib and regorafenib, mainly considering the substitution effect following a robust procedure. All complexes were structurally confirmed by spectroscopic means and thermal analysis. Specially, five cocrystals with three deuterated, named sorafenib·DMSO, donafenib·DMSO, deuregorafenib·DMSO, 6·DMSO, and 7·DMSO were obtained. The crystal structures revealed that all host molecules consistently bonded with DMSO in intermolecular interaction in a 1:1 stoichiometry. However, further comparison with documented DMSO complexes and parent motifs presented some arrangement diversities especially for 6·DMSO which offered a counter-example to previous rules. Major changes in the orientation of meta-substituents and the packing stability for sorafenib·DMSO and deuregorafenib·DMSO were rationalized by theory analysis and computational energy calculation. Cumulative data implied that the planarization of two aryl planes in diarylureas may play a crucial role in cocrystallization. Also, a polymorph study bridged the transformation between these ureas and their DMSO complexes.

Design, Synthesis, and Anti-Fungal Evaluation of Heterocyclic Benzoxazole Derivatives

“…The crystal structures of 4ac – 4bc were determined by single-crystal X-ray diffraction [ 27 ]. A total of 100 mg of the compound 4ac – 4bc was dissolved in 3 mL of ethyl acetate, and the solution was placed in a 25 mL micro-reaction bottle.…”

Synthetic Approaches to the New Drugs Approved During 2022

“…228 A gram-scale synthesis of donafenib was recently disclosed by Luo and co-workers (Scheme 55). 229 The synthetic sequence commenced with amidation of methyl ester 31. 230,231 The oral, smallmolecule cancer treatment was granted accelerated approval in the US by the USFDA in late September 2022 and serves as an irreversible inhibitor and selective covalent binder of fibroblast growth factor receptor (FGFR) 1−4.…”

“…A gram-scale synthesis of donafenib was recently disclosed by Luo and co-workers (Scheme ). The synthetic sequence commenced with amidation of methyl ester 31.2 using methan-d 3 -amine hydrochloride ( 31.1 ) as the deuterium source, affording CD 3 -amide 31.3 in high yield (98%). S N Ar displacement with aminophenol 31.4 in DMSO provided diaryl ether 31.5 .…”

Phenothiazine appended thiophene derivative: a trilateral approach to copper ion detection in living cells and aqueous samples

“…Consequently, it provides a compelling depiction of intramolecular charge transfer (ICT) dynamics, specically involving electron transfer from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO). 39,40 Within the PTZ-SCN-Cu 2+ complex, it is evident that the HOMO's electron density is localized around the metal ion, while the LUMO's electron density predominantly resides within the thiophene moiety, potentially mitigating any intramolecular charge transfer between thiophene acetonitrile and phenothiazine (Fig. 12).…”