Parallel Synthesis of Piperazine Tethered Thiazole Compounds with Antiplasmodial Activity.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Antimalarials*/chemistry; Piperazine ; Thiazoles/chemistry ; Chloroquine/pharmacology ; Chloroquine/chemistry ; Plasmodium falciparum

Thiazole and piperazine are two important heterocyclic rings that play a prominent role in nature and have a broad range of applications in agricultural and medicinal chemistry. Herein, we report the parallel synthesis of a library of diverse piperazine-tethered thiazole compounds. The reaction of piperazine with newly generated 4-chloromethyl-2-amino thiazoles led to the desired piperazine thiazole compounds with high purities and good overall yields. Using a variety of commercially available carboxylic acids, the parallel synthesis of a variety of disubstituted 4-(piperazin-1-ylmethyl)thiazol-2-amine derivatives is described. the screening of the compounds led to the identification of antiplasmodial compounds that exhibited interesting antimalarial activity, primarily against the Plasmodium falciparum chloroquine-resistant Dd2 strain. The hit compound 2291-61 demonstrated an antiplasmodial EC 50 of 102 nM in the chloroquine-resistant Dd2 strain and a selectivity of over 140.

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R41 AI120351 United States AI NIAID NIH HHS

Keywords: antiplasmodial activity; combinatorial chemistry; heterocyclic compounds; malaria; solid-phase synthesis; thiazole tethered piperazine

0 (Antimalarials)
1RTM4PAL0V (Piperazine)
0 (Thiazoles)
886U3H6UFF (Chloroquine)

Date Created: 20231223 Date Completed: 20231225 Latest Revision: 20240210

20250114

PMC10743568

10.3390/ijms242417414

38139243