Synthesis and biological evaluation of substituted pyrazoles as blockers of divalent metal transporter 1 (DMT1)

…, M Mattice, A Brownlie-Cutts, J Fu, LG Ratkay…

Index: Cadieux, Jay A.; Zhang, Zaihui; Mattice, Maryanne; Brownlie-Cutts, Alison; Fu, Jianmin; Ratkay, Laszlo G.; Kwan, Rainbow; Thompson, Jay; Sanghara, Joseph; Zhong, Jing; Goldberg, Y. Paul Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 1 p. 90 - 95

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Citation Number: 13

Abstract

Three distinct series of substituted pyrazole blockers of divalent metal transporter 1 (DMT1) were elaborated from the high-throughput screening pyrazolone hit 1. Preliminary hit-to-lead efforts revealed a preference for electron-withdrawing substituents in the 4-amido-5- hydroxypyrazole series 6a–l. In turn, this preference was more pronounced in a series of 4- aryl-5-hydroxypyrazoles 8a–j. The representative analogs 6f and 12f were found to be ...