Experimental and Computational Investigation of the Oxime Bond Stereochemistry in c-Jun N-terminal Kinase 3 Inhibitors 11 H -Indeno[1,2- b ]quinoxalin-11-one Oxime and Tryptanthrin-6-oxime.
Vladislava V MatveevskayaDmitry I PavlovAnastasia R KovrizhinaTaisiya S SukhikhEvgeniy H SadykovPavel V DorovatovskiiVladimir A LazarenkoAndrei I KhlebnikovAndrei S PotapovPublished in: Pharmaceutics (2023)
11 H -Indeno[1,2- b ]quinoxalin-11-one oxime ( IQ-1 ) and tryptanthrin-6-oxime are potent c-Jun N-terminal kinase 3 (JNK-3) inhibitors demonstrating neuroprotective, anti-inflammatory and anti-arthritic activity. However, the stereochemical configuration of the oxime carbon-nitrogen double bond ( E - or Z -) in these compounds was so far unknown. In this contribution, we report the results of the determination of the double bond configuration in the solid state by single crystal X-ray diffraction and in solution by 1D and 2D NMR techniques and DFT calculations. It was found that both in the solid state and in solution, IQ-1 adopts the E -configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed Z -configuration that could be stabilized only by an intramolecular hydrogen bond.
Keyphrases
- solid state
- anti inflammatory
- density functional theory
- transition metal
- magnetic resonance
- signaling pathway
- molecular dynamics
- molecular dynamics simulations
- molecular docking
- energy transfer
- crystal structure
- solid phase extraction
- induced apoptosis
- molecularly imprinted
- contrast enhanced
- monte carlo
- dual energy