Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series

Dihydroorotate dehydrogenase (DHODH) has been clinically validated as a target for the development of new antimalarials. Experience with clinical candidate triazolopyrimidine DSM265 (1) suggested that DHODH inhibitors have great potential for use in prophylaxis, which represents an unmet need in the...

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Veröffentlicht in:	Journal of medicinal chemistry 2021-05, Vol.64 (9), p.6085-6136
Hauptverfasser:	Palmer, Michael J, Deng, Xiaoyi, Watts, Shawn, Krilov, Goran, Gerasyuto, Aleksey, Kokkonda, Sreekanth, El Mazouni, Farah, White, John, White, Karen L, Striepen, Josefine, Bath, Jade, Schindler, Kyra A, Yeo, Tomas, Shackleford, David M, Mok, Sachel, Deni, Ioanna, Lawong, Aloysus, Huang, Ann, Chen, Gong, Wang, Wen, Jayaseelan, Jaya, Katneni, Kasiram, Patil, Rahul, Saunders, Jessica, Shahi, Shatrughan P, Chittimalla, Rajesh, Angulo-Barturen, Iñigo, Jiménez-Díaz, María Belén, Wittlin, Sergio, Tumwebaze, Patrick K, Rosenthal, Philip J, Cooper, Roland A, Aguiar, Anna Caroline Campos, Guido, Rafael V. C, Pereira, Dhelio B, Mittal, Nimisha, Winzeler, Elizabeth A, Tomchick, Diana R, Laleu, Benoît, Burrows, Jeremy N, Rathod, Pradipsinh K, Fidock, David A, Charman, Susan A, Phillips, Margaret A
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antimalarials - chemistry Antimalarials - pharmacology Dihydroorotate Dehydrogenase Drug Design Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Mice Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors Plasmodium falciparum - drug effects Pyrroles - chemistry Pyrroles - pharmacology Structure-Activity Relationship
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