title: Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-alpha and IL-6 inhibitors.
abstract: In the present article, we have synthesized three different series of pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl-D-glucal/chromone-3-carbaldehyde with heteroaromatic amines. All synthesized compounds were evaluated for their anti-inflammatory activity against TNF-alpha and IL-6. Out of 28 compounds screened, 40, 51, 52 and 56 exhibited promising activity against IL-6 with 60-65% inhibition at 10 microM concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC(50)'s of 0.2, 0.3 and 0.16 microM, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of >100 microM.
authors.affiliation: Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1, Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Bharate
authors.forename: Tushar R
authors.initials: TR
authors.lastname: Mahajan
authors.forename: Yogesh R
authors.initials: YR
authors.lastname: Gole
authors.forename: Mahesh
authors.initials: M
authors.lastname: Nambiar
authors.forename: T T
authors.initials: TT
authors.lastname: Matan
authors.forename: Asha
authors.initials: A
authors.lastname: Kulkarni-Almeida
authors.forename: Sarala
authors.initials: S
authors.lastname: Balachandran
authors.forename: H
authors.initials: H
authors.lastname: Junjappa
authors.forename: Arun
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors