Abstract
Quinazoline-2,4(1H, 3H)-diones exhibit a wealth of biological activities including antitumor proliferation. We established an improved method for the synthesis of quinazoline-2,4(1H, 3H)-dione derivatives with three points of molecular diversity. Data indicate that compounds 60 (average logGI50=−6.1), 65 (average logGI50=−6.13), 69 (average logGI50 = −6.44), 72 (average logGI50 = −6.39), and 86 (average logGI50 = −6.45) significantly inhibited the in vitro growth of 60 human tumor cell lines tested. Structure–activity relationship analyses indicate that chlorophenethylureido is the necessary substituent at the D3 diversity point (7-position of quinazoline-2,4(1H, 3H)-dione), in particular, o-chlorophenethylurea (69) achieved optimal activity. o- or m-Chlorophenethyl substitutions (69 and 72) at the D2 diversity point (3-position of quinazo line-2,4(1H, 3H)-dione) gave the most potent compounds. Methoxyl and 4-methylpiperazin-1-yl substitution at the D1 diversity point (6-position of quinazoline-2,4(1H, 3H)-dione skeleton) may yield better activity than other groups. The quinazoline-2,4(1H, 3H)-dione scaffold can be effectively replaced by 2H-benzo[b][1,4]thiazin-3(4H)-one.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
