Synthesis of 2-Aminopyridopyrimidinones and Their Plasmepsin I, II, IV Inhibition Potency
Chemistry of Heterocyclic Compounds 2020
Dace Rasiņa, Georgijs Stakanovs, Iveta Kaņepe-Lapsa, Raitis Bobrovs, Kristaps Jaudzems, Aigars Jirgensons

[Figure not available: see fulltext.] Malarial aspartic protease, plasmepsin (Plm), is perspective antimalarial drug target. Following up our previosly identified 2-aminoquinazolin-4(3H)-one-based inhibitors, 2-aminopyrido[2,3-d]-, -[3,2-d]-, and -[4,3-d]pyrimidin-4(3H)-ones bearing subpocket-specific substituents at position 7 were prepared and tested for their Plm I, II, IV inhibition potency. The position of the nitrogen atom in 2-aminopyridopyrimidinones plays significant role in the inhibitory potency against Plms. Pyrido[2,3-d]pyrimidin-4(3H)-one derivatives showed poor inhibitory potency against Plms I, II, IV irrespectively of the substituent at position 7. However, pyrido[4,3-d]pyrimidin-4(3H)-ones and pyrido[3,2-d]pyrimidin-4(3H)-ones were more appropriate scaffolds for Plm inhibitor development. Particularly, 2-amino-7-[4-(3-phenylpropyl)phenyl]-3-[(tetrahydrofuran-2-yl)methyl]pyrido[3,2-d]pyrimidin-4(3H)-one showed very high potency against Plm IV subtype and high selectivity against human aspartic protease, cathepsin D.


Atslēgas vārdi
2-aminopyrido[2,3-d]pyrimidin-4(3H)-ones, 2-aminopyrido[3,2-d]pyrimidin-4(3H)-ones, 2-aminopyrido[4,3-d]pyrimidin-4(3H)- ones, malaria, plasmepsins
DOI
10.1007/s10593-020-02731-3
Hipersaite
https://link-springer-com.resursi.rtu.lv/article/10.1007/s10593-020-02731-3

Rasiņa, D., Stakanovs, G., Kaņepe-Lapsa, I., Bobrovs, R., Jaudzems, K., Jirgensons, A. Synthesis of 2-Aminopyridopyrimidinones and Their Plasmepsin I, II, IV Inhibition Potency. Chemistry of Heterocyclic Compounds, 2020, Vol. 56, No. 6, 786.-792.lpp. ISSN 0009-3122. e-ISSN 1573-8353. Pieejams: doi:10.1007/s10593-020-02731-3

Publikācijas valoda
English (en)
RTU Zinātniskā bibliotēka.
E-pasts: uzzinas@rtu.lv; Tālr: +371 28399196