The identification of compounds able to inhibit the NAD salvage pathway is experiencing a growing popularity as it has been proposed to be a novel target for antitumoral and anti-inflammatory drugs. In this manuscript, we used the copper-catalyzed [3+2] cycloaddition between azides and alkynes (click chemistry) to identify novel NAMPT inhibitors with a triazole-containing tail group. 720 compounds were synthesized in the first round, allowing the identification of 17 hit compounds. The second round of optimization brought about the discovery of compound 43 which displayed a cytotoxicity of 20 nM on neuroblastoma cancer cells and an inhibition of NAMPT of 114 nM.
Identification of a novel NAMPT inhibitor by combinatorial click chemistry and chemical refinement / Theeramunkong, S; Galli, U.; Grolla, A. A.; Caldarelli, A.; Travelli, C.; Massarotti, A.; Troiani, M. P.; Alisi, M. A.; Orsomando, Giuseppe; Genazzani, A. A.; Tron, G. C.. - In: MEDCHEMCOMM. - ISSN 2040-2503. - STAMPA. - 6:10(2015), pp. 1891-1897. [10.1039/c5md00261c]
Identification of a novel NAMPT inhibitor by combinatorial click chemistry and chemical refinement
ORSOMANDO, Giuseppe;
2015-01-01
Abstract
The identification of compounds able to inhibit the NAD salvage pathway is experiencing a growing popularity as it has been proposed to be a novel target for antitumoral and anti-inflammatory drugs. In this manuscript, we used the copper-catalyzed [3+2] cycloaddition between azides and alkynes (click chemistry) to identify novel NAMPT inhibitors with a triazole-containing tail group. 720 compounds were synthesized in the first round, allowing the identification of 17 hit compounds. The second round of optimization brought about the discovery of compound 43 which displayed a cytotoxicity of 20 nM on neuroblastoma cancer cells and an inhibition of NAMPT of 114 nM.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
