Pyrazoline based MAO inhibitors: Synthesis, biological evaluation and SAR studies

• Published in: Bioorganic & medicinal chemistry letters 2011-07, Vol.21 (14), p.4296-4300
• Main Authors: Jagrat, Monika, Behera, Jagannath, Yabanoglu, Samiye, Ercan, Ayse, Ucar, Gulberk, Sinha, Barij Nayan, Sankaran, Vadivelan, Basu, Arijit, Jayaprakash, Venkatesan
• Format: Article
• Language: English
• Subjects: Anticonvulsants. Antiepileptics. Antiparkinson agents; Binding Sites; Biological and medical sciences; Computer Simulation; Docking; Humans; MAO; Medical sciences; Monoamine Oxidase - chemistry; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Protein Isoforms - antagonists & inhibitors; Protein Isoforms - metabolism; Protein Structure, Tertiary; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazolines; Selectivity; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.05.057

Pyrazoline derivatives with unsubstituted ring A and substituted ring C ( 5– 16) were found to be potent inhibitors of MAO-A isoform with SI MAO-A in the order of 10 3 and 10 4. Twenty-two pyrazoline derivatives were synthesized and tested for their human MAO (hMAO) inhibitory activity. Twelve molecules with unsubstituted ring A and substituted ring C ( 5– 16) were found to be potent inhibitors of hMAO-A isoform with SI MAO-A in the order 10 3 and 10 4. Ten molecules with unsubstituted ring A and without ring C ( 21– 30), in which eight molecules ( 21, 23– 26, and 28– 30) were selective for hMAO-A, one for hMAO-B ( 22) and the other one non-selective ( 27). Presence of ring C increases potency as well as SI towards hMAO-A; however its absence decreases both potency and SI towards hMAO-A and hMAO-B.