Year-end Sale % OFF 
Abstract
Efficient microwave-assisted chemical processes were applied to the synthesis of an array of novel N-(4-methoxyphenylamino)-2-methyl benzo-, pyrido- or pyrazino-thieno[3,2-d]pyrimidin-4-amine derivatives. These heteroaromatic systems were envisioned as potent bioisosteric analogues of MPC-6827, an anticancer agent previously developed until phase II clinical studies. A brief evaluation and comparison of their antiproliferative activity on HT-29 and Caco-2, two human colorectal cancer cell lines, were also reported. At the tested concentrations (5 and 10 µM), thieno[3,2-d]pyrimidin-4-amines 4a and 4c exhibited an inhibitory effect similar to MPC-6827 on human colorectal cancer cell proliferation.
Highlights
Due to their presence in numerous biologically active compounds, quinazoline derivatives are of particular interest for medicinal chemistry and remain a major research area in organic chemistry [1,2,3,4,5]
MPC-6827, named Azixa or verubulin, is a microtubule-destabilizing agent exhibiting a dual mode of action, leading to apoptosis by blocking cell cycle and to growth inhibition on several types of cancer such as breast, colon and ovarian cancers [8,9,10]
MPC-6827 is known to reduce blood supply to the tumors [11]. This benzo[e]pyrimidine emerged as a good candidate for phase I and phase II clinical trials in patients with metastatic melanoma and glioblastoma multiforme [12,13,14]
Summary
Due to their presence in numerous biologically active compounds, quinazoline derivatives are of particular interest for medicinal chemistry and remain a major research area in organic chemistry [1,2,3,4,5]. MPC-6827 is known to reduce blood supply to the tumors [11] Based on these data, this benzo[e]pyrimidine emerged as a good candidate for phase I and phase II clinical trials in patients with metastatic melanoma and glioblastoma multiforme [12,13,14]. This benzo[e]pyrimidine emerged as a good candidate for phase I and phase II clinical trials in patients with metastatic melanoma and glioblastoma multiforme [12,13,14] Despite these investigations revealing some cardiotoxicity and leading to the suspension of clinical development in phase II [15], MPC-6827 remains an excellent model for the design of potential cytotoxic agents [16]
Sign-in/Register to view highlights & summary 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.
