title: Synthesis and evaluation of quinazolin-4-ones as hypoxia-inducible factor-1α inhibitors.
abstract: Quinazolin-4-one 1 was identified as an inhibitor of the HIF-1α transcriptional factor from a high-throughput screen. HIF-1α up-regulation is common in many cancer cells. In this Letter, we describe an efficient one-pot sequential reaction for the synthesis of quinazolin-4-one 1 analogues. The structure-activity relationship (SAR) study led to the 5-fold more potent analogue, 16.
authors.affiliation: NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Dr., Rockville, MD 20850, USA. huangwe@mail.nih.gov
authors.forename: Wenwei
authors.initials: W
authors.lastname: Huang
authors.forename: Ruili
authors.initials: R
authors.lastname: Huang
authors.forename: Matias S
authors.initials: MS
authors.lastname: Attene-Ramos
authors.forename: Srilatha
authors.initials: S
authors.lastname: Sakamuru
authors.forename: Erika E
authors.initials: EE
authors.lastname: Englund
authors.forename: James
authors.initials: J
authors.lastname: Inglese
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.forename: Menghang
authors.initials: M
authors.lastname: Xia
mesh_terms: D060326:Chemistry Techniques, Synthetic; D057166:High-Throughput Screening Assays; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052999:Quinazolinones