Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-alpha and IL-6 inhibitors.
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.
Bharate
Sandip B
SB
Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1, Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.
Mahajan
Tushar R
TR
Gole
Yogesh R
YR
Nambiar
Mahesh
M
Matan
T T
TT
Kulkarni-Almeida
Asha
A
Balachandran
Sarala
S
Junjappa
H
H
Balakrishnan
Arun
A
Vishwakarma
Ram A
RA
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors