EW-7197

EW-7197 is a novel ALK-5 kinase inhibitor as well as TGF-β Type I Receptor Kinase Inhibitor. Study has shown that it can potently inhibit the breast to lung metastasis. Mice study has demonstrated that EW-7197 inhibited Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice and 4T1 orthotopic-grafted mice. EW-7197 also inhibited the epithelial-to-mesenchymal transition (EMT) in both TGFβ-treated breast cancer cells and 4T1 orthotopic-grafted mice. Furthermore, EW-

Vactosertib is under investigation in clinical trial NCT03724851 (Vactosertib in Combination With Pembrolizumab in Metastatic Colorectal or Gastric Cancer).|Vactosertib is an orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. Upon oral administration, vactosertib inhibits the activity of TGFBR1 and prevents TGF-beta/TGFBR1-mediated signaling. This suppresses tumor growth in TGFBR1-overexpressing tumor cells. TGFBR1, which is overexpressed in a variety of tumor cell types, plays a key role in tumor cell proliferation. Expression of TGF-beta promotes tumor cell proliferation, enhances the migration of tumor cells and suppresses the response of the host immune system to tumor cells.

General procedure: To a stirred solution of 11 (13.14 mmol) in 1, 2-dichloroethane (240 mL) were added appropriate substituted anilines (19.71 mmol) and AcOH (13.14 mmol), and the mixture was heated to reflux for 2 h under nitrogen atmosphere. The reaction mixture was cooled to 0 C, and MeOH (60 mL) and THF (20 mL) were added. To it, (AcO)3BHNa (26.20 mmol) or NaBH4 (52.56 mmol) was added portionwise, and then the reaction mixture was allowed to warm to room temperature and stirred for an additional 3 h. The pH of the reaction mixture was adjusted to 7-8 at 0 C with 1 NHCl, and then the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2× 300 mL). The combined organic layers was washed with brine (300 mL) and dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on silica gel to afford the titled compounds as a solid.To a stirred solution of 13ain CH2Cl2 (1 mL) cooled 0 C, was added 1.0 M HCl in Et2O (1.9 mL, 1.88 mmol) undernitrogen atmosphere. The mixture was stirred at room temperature for 5 min and evaporated todryness under reduced pressure. The solid was dried using a rotary evaporator in vacuo at 40 C for 16 h to afford the titled compound as a yellow solid. Yield 97%.

Molecular Weight:399.4
XLogP3:3.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:5
Exact Mass:399.16077177
Monoisotopic Mass:399.16077177
Topological Polar Surface Area:83.8
Heavy Atom Count:30
Complexity:566
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes