Trisubstituted thiazoles as potent and selective inhibitors of Plasmodium falciparum protein kinase G (PfPKG).

Tsagris, Denise J; Birchall, Kristian; Bouloc, Nathalie; Large, Jonathan M; Merritt, Andy; Smiljanic-Hurley, Ela; Wheldon, Mary; Ansell, Keith H; Kettleborough, Catherine; Whalley, David; Stewart, Lindsay B; Bowyer, Paul W; Baker, David A; Osborne, Simon A

Tsagris, Denise J; Birchall, Kristian; Bouloc, Nathalie; Large, Jonathan M; Merritt, Andy; Smiljanic-Hurley, Ela; Wheldon, Mary; Ansell, Keith H; Kettleborough, Catherine; Whalley, David; Stewart, Lindsay B; Bowyer, Paul W; Baker, David A; Osborne, Simon A.

Afiliação

Tsagris DJ; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK. Electronic address: denise.tsagris@lifearc.org.
Birchall K; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Bouloc N; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Large JM; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Merritt A; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Smiljanic-Hurley E; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Wheldon M; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Ansell KH; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Kettleborough C; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Whalley D; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
Stewart LB; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Bowyer PW; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Baker DA; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Osborne SA; LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.

Bioorg Med Chem Lett ; 28(19): 3168-3173, 2018 10 15.

Article em En | MEDLINE | ID: mdl-30174152

ABSTRACT

ABSTRACT

A series of trisubstituted thiazoles have been identified as potent inhibitors of Plasmodium falciparum (Pf) cGMP-dependent protein kinase (PfPKG) through template hopping from known Eimeria PKG (EtPKG) inhibitors. The thiazole series has yielded compounds with improved potency, kinase selectivity and good in vitro ADME properties. These compounds could be useful tools in the development of new anti-malarial drugs in the fight against drug resistant malaria.

Assuntos

Antimaláricos/farmacologia; Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores; Plasmodium falciparum/enzimologia; Inibidores de Proteínas Quinases/farmacologia; Proteínas de Protozoários/antagonistas & inibidores; Tiazóis/farmacologia; Alquilação; Antimaláricos/química; Humanos; Oxirredução; Inibidores de Proteínas Quinases/química; Relação Estrutura-Atividade; Tiazóis/química

Palavras-chave

Malaria; PfPKG; Plasmodium falciparum; Thiazole

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Tiazóis / Proteínas de Protozoários / Proteínas Quinases Dependentes de GMP Cíclico / Inibidores de Proteínas Quinases / Antimaláricos Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2018 Tipo de documento: Article

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