Synthesis and evaluation of highly selective quinazoline-2,4-dione ligands for sphingosine-1-phosphate receptor 2

Abstract

A series of twenty-nine new quinazoline-2,4-dione compounds were synthesized and their IC50 values of binding toward sphingosine 1-phosphate receptor 2 (S1PR2) were determined using a [32P]S1P binding assay. Seven compounds...

Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas

“…The quinazoline-2,4-dione fragment is part of many clinical candidates: selurampanel (an AMPA/kainate receptor antagonist for epilepsy treatment) [1,2], elinogrel (a P2Y12 receptor antagonist for the treatment of cardiovascular atherothrombotic disease) [3][4][5], zenarestat (an aldose reductase inhibitor for the management of diabetic peripheral neuropathy) [6,7], ketanserin (a 5-HT2 receptor antagonist with the hypotensive action) [8,9], carotegrast (α4 integrin antagonist for the treatment of ulcerative colitis) [10,11], senaparib (a PARP inhibitor for the therapy of solid tumors) [12][13][14], and BMS-986142 (a Bruton's tyrosine kinase inhibitor for the treatment of rheumatoid arthritis) [15][16][17]. In addition, quinazoline-2,4-dione derivatives were recognized as inhibitors of several cancer-related enzymes [18] (including carbonic anhydrases IX and XII [19], histone deacetylase-6 [20], VEGFR-2 [21], tankyrases [22], aminopeptidase [23]) and as modulators of autoimmune processes [24][25][26][27]. Moreover, they are widely used to combat viral [28,29], bacterial [30][31][32], parasitic [33][34][35], and fungal [36] infections.…”