Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6<i>H</i>-benzo[<i>e</i>]pyrimido[5,4-<i>b</i>][1,4]...

ID: ALA4610122

Journal: J Med Chem

Title: Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one Scaffold.

Authors: Ferguson FM, Liu Y, Harshbarger W, Huang L, Wang J, Deng X, Capuzzi SJ, Muratov EN, Tropsha A, Muthuswamy S, Westover KD, Gray NS.

Abstract: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that is overexpressed in gastrointestinal cancers, including esophageal, gastric, colorectal, and pancreatic cancers. DCLK1 is also used as a marker of tuft cells, which regulate type II immunity in the gut. However, the substrates and functions of DCLK1 are understudied. We recently described the first selective DCLK1/2 inhibitor, DCLK1-IN-1, developed to aid the functional characterization of this important kinase. Here we describe the synthesis and structure-activity relationships of 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one DCLK1 inhibitors, resulting in the identification of DCLK1-IN-1.

CiteXplore: 32530623

DOI: 10.1021/acs.jmedchem.0c00596

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