Design, synthesis, and evaluation of indoleamin-2,3-dioxygenase 1 inhibition activity of novel 5/6-amino indazole derivatives with amide template.

Ngo Xuan Hoang; Tam Thuy Lu Vo; Van-Hai Hoang; Tiep K. Nguyen; Ji Hae Seo; Phuong-Thao Tran

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme participating in tryptophan metabolism that has been implicated in numerous cancers. In the present study, a series of novel 5/6-amino indazole derivatives having amide linker were designed, synthesized, and evaluated for IDO1 inhibitory activity. The compounds were initially designed based on the known structural feature of IDO1 active site, and the important role of the indazole scaffold in interaction with IDO1 active site. Thirteen compounds exibited the moderate to excellent inhibitory activity (49% to 100% at the concentration of 1.0 mM). One of them, compound, 2-(6-amino-1H-indazol-1-yl)-N-(4-chlorophenyl) acetamide (19d), with chloro substituents group at para- position increased the activity upto 100%, equal to that value of the positive control, IDO5L. This research suggests that 5/6-amino indazole moiety combined with amide template is a potential scaffold for IDO1 inhibition as anti-cancer agents.

AMIDE derivatives; ACETAMIDE derivatives; INDOLEAMINE 2,3-dioxygenase; AZOLES; ANTINEOPLASTIC agents; ACETAMIDE; TRYPTOPHAN

Pharmaceutical Sciences Asia, 2023, Vol 50, Issue 2, p147

2586-8195

Academic Journal

10.29090/psa.2023.01.22.309