Synthesis, crystal structure, and biological evaluation of optically active 2‐amino‐4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐3‐carbonitriles: Antiepileptic, antidiabetic, and anticholinergics potentials

• Published in: Archiv der Pharmazie (Weinheim) 2019-02, Vol.352 (2), p.e1800317-n/a
• Main Authors: Maharramov, Abel, Kaya, Ruya, Taslimi, Parham, Kurbanova, Malahat, Sadigova, Arzu, Farzaliyev, Vagif, Sujayev, Afsun, Gulçin, İlhami
• Format: Article
• Language: English
• Subjects: Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; antidiabetic potential; Antidiabetics; asymmetric synthesis; carbonic anhydrase; Cholinergic Antagonists - chemical synthesis; Cholinergic Antagonists - chemistry; Cholinergic Antagonists - pharmacology; Crystallization; Humans; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; metabolic enzymes; Nitriles - chemical synthesis; Nitriles - chemistry; Nitriles - pharmacology; optically active 4H‐chromenes; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201800317

In the presence of chiral organic catalysts, the optically active 4H‐chromine was synthesized from the multicomponent condensation of 5,5‐dimethylcyclohexane‐1,3‐dione with malononitrile and methylene‐active compound, and the specific angle of rotation of the compounds was determined in the AUTOPOL‐III polarimeter and their structures were confirmed by the X‐ray spectroscopic analysis method. These optically active 2‐amino‐4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐3‐carbonitriles were effective inhibitors of α‐glycosidase, the cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzymes with Ki values in the range of 21.33 ± 1.11 to 40.24 ± 10.78 μM for hCA I, 28.91 ± 6.51 to 59.97 ± 15.62 μM for hCA II, 18.16 ± 3.18 to 66.57 ± 1.36 μM for α‐glycosidase, and 8.68 ± 0.93 to 102.61 ± 24.96 μM for AChE. In the presence of chiral organic catalysts, the optically active 4H‐chromine was synthesized from multicomponent condensation of 5,5‐dimethylcyclohexane‐1,3‐dione with malononitrile and methylene‐active compound. The resulting eugenol bearing oxypropanolamine derivatives were effective inhibitors of α‐glycosidase, cytosolic carbonic anhydrases I and II, and acetylcholinesterase.