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


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
13 05 2021
Historique:
pubmed: 21 4 2021
medline: 16 6 2021
entrez: 20 4 2021
Statut: ppublish

Résumé

Dihydroorotate dehydrogenase (DHODH) has been clinically validated as a target for the development of new antimalarials. Experience with clinical candidate triazolopyrimidine DSM265 (

Identifiants

pubmed: 33876936
doi: 10.1021/acs.jmedchem.1c00173
pmc: PMC8171248
mid: NIHMS1702324
doi:

Substances chimiques

Antimalarials 0
Dihydroorotate Dehydrogenase 0
Enzyme Inhibitors 0
Pyrroles 0
Oxidoreductases Acting on CH-CH Group Donors EC 1.3.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

6085-6136

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI103947
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI109023
Pays : United States
Organisme : NIH HHS
ID : S10 OD025018
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089688
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI139179
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007020
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI093380
Pays : United States

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Auteurs

Michael J Palmer (MJ)

Medicines for Malaria Venture, 1215 Geneva, Switzerland.

Xiaoyi Deng (X)

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390-9135, United States.

Shawn Watts (S)

Schrodinger, Inc., 120 West 45th St, 17th Floor, New York, New York 100036-4041, United States.

Goran Krilov (G)

Schrodinger, Inc., 120 West 45th St, 17th Floor, New York, New York 100036-4041, United States.

Aleksey Gerasyuto (A)

Schrodinger, Inc., 120 West 45th St, 17th Floor, New York, New York 100036-4041, United States.

Sreekanth Kokkonda (S)

Departments of Chemistry and Global Health, University of Washington, Seattle, Washington 98195, United States.

Farah El Mazouni (F)

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390-9135, United States.

John White (J)

Departments of Chemistry and Global Health, University of Washington, Seattle, Washington 98195, United States.

Karen L White (KL)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Josefine Striepen (J)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.

Jade Bath (J)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.

Kyra A Schindler (KA)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.

Tomas Yeo (T)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.

David M Shackleford (DM)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Sachel Mok (S)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.

Ioanna Deni (I)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.

Aloysus Lawong (A)

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390-9135, United States.

Ann Huang (A)

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390-9135, United States.

Gong Chen (G)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Wen Wang (W)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Jaya Jayaseelan (J)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Kasiram Katneni (K)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Rahul Patil (R)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Jessica Saunders (J)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Shatrughan P Shahi (SP)

Syngene International Ltd, Bangalore 560099, India.

Rajesh Chittimalla (R)

Syngene International Ltd, Bangalore 560099, India.

Iñigo Angulo-Barturen (I)

TAD, Biscay Science and Technology Park, Astondo Bidea, BIC Bizkaia Bd 612, Derio, 48160 Bizkaia, Basque Country, Spain.

María Belén Jiménez-Díaz (MB)

TAD, Biscay Science and Technology Park, Astondo Bidea, BIC Bizkaia Bd 612, Derio, 48160 Bizkaia, Basque Country, Spain.

Sergio Wittlin (S)

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.
University of Basel, 4002 Basel, Switzerland.

Patrick K Tumwebaze (PK)

Infectious Diseases Research Collaboration, Kampala, Uganda.

Philip J Rosenthal (PJ)

Department of Medicine, University of California, San Francisco, California 94143, United States.

Roland A Cooper (RA)

Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, California 94901, United States.

Anna Caroline Campos Aguiar (ACC)

University of Sao Paulo, Sao Carlos Institute of Physics, Sáo Carlos, SP 13560-970, Brazil.

Rafael V C Guido (RVC)

University of Sao Paulo, Sao Carlos Institute of Physics, Sáo Carlos, SP 13560-970, Brazil.

Dhelio B Pereira (DB)

Tropical Medicine Research Center of Rondonia, Av. Guaporé, 215, Porto Velho, RO 76812-329, Brazil.

Nimisha Mittal (N)

Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States.

Elizabeth A Winzeler (EA)

Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States.

Diana R Tomchick (DR)

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390-9135, United States.

Benoît Laleu (B)

Medicines for Malaria Venture, 1215 Geneva, Switzerland.

Jeremy N Burrows (JN)

Medicines for Malaria Venture, 1215 Geneva, Switzerland.

Pradipsinh K Rathod (PK)

Departments of Chemistry and Global Health, University of Washington, Seattle, Washington 98195, United States.

David A Fidock (DA)

Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.
Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.

Susan A Charman (SA)

Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Margaret A Phillips (MA)

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390-9135, United States.

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