524708-22-3

Upstream product

• 1369967-37-2 C₂₇H₂₇N₃O₃S₂ 
• 67-64-1 acetone 
• 1369967-29-2 tert-butyl 2-amino-3-(benzo[d]thiazol-2-yl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 103-80-0 phenylacetyl chloride 

Relevant academic research and scientific papers

Synthesis, biological evaluation, and structure-activity relationships of a novel class of apurinic/apyrimidinic endonuclease 1 inhibitors

APE1 is an essential protein that operates in the base excision repair (BER) pathway and is responsible for a‰￥ 95% of the total apurinic/apyrimidinic (AP) endonuclease activity in human cells. BER is a major pathway that copes with DNA damage induced by several anticancer agents, including ionizing radiation and temozolomide. Overexpression of APE1 and enhanced AP endonuclease activity have been linked to increased resistance of tumor cells to treatment with monofunctional alkylators, implicating inhibition of APE1 as a valid strategy for cancer therapy. We report herein the results of a focused medicinal chemistry effort around a novel APE1 inhibitor, N-(3-(benzo[d]thiazol-2-yl)-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-c] pyridin-2-yl)acetamide (3). Compound 3 and related analogues exhibit single-digit micromolar activity against the purified APE1 enzyme and comparable activity in HeLa whole cell extract assays and potentiate the cytotoxicity of the alkylating agents methylmethane sulfonate and temozolomide. Moreover, this class of compounds possesses a generally favorable in vitro ADME profile, along with good exposure levels in plasma and brain following intraperitoneal dosing (30 mg/kg body weight) in mice. This article not subject to U.S. Copyright. Published 2012 by the American Chemical Society.

INHIBITORS OF HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE 1

Disclosed are inhibitors of human APE1, for example, of formula (I), wherein A, B, X, R2, and R3 are as defined herein, that are useful in treating an APE1 mediated disease or disorder, e.g., cancer. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the invention, a method of treating cancer in a mammal and a method of potentiating treatment of cancer.