ArticleBioorganic & medicinal chemistry2009
Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.
Article in Bioorganic & medicinal chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 35 citations in OpenAlex.
- The antitumor promise of furo[2,3-RSC advances · 2026Review
- An efficient diastereoselective synthesis of novel fused 5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones via one-pot three-component reaction.Molecular diversity · 2022Article
- Transformational machine learning: Learning how to learn from many related scientific problems.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Hybrid Drugs-A Strategy for Overcoming Anticancer Drug Resistance?Molecules (Basel, Switzerland) · 2021Review
- Discovery and preclinical evaluation of 7-benzyl-N-(substituted)-pyrrolo[3,2-d]pyrimidin-4-amines as single agents with microtubule targeting effects along with triple-acting angiokinase inhibition as antitumor agents.Bioorganic & medicinal chemistry · 2017Article
- Structure-activity correlations for three pyrido[2,3-d]pyrimidine antifolates binding to human and Pneumocystis carinii dihydrofolate reductase.Acta crystallographica. Section F, Structural biology communications · 2015Article
- The design and discovery of water soluble 4-substituted-2,6-dimethylfuro[2,3-d]pyrimidines as multitargeted receptor tyrosine kinase inhibitors and microtubule targeting antitumor agents.Bioorganic & medicinal chemistry · 2014Article
- Discovery of antitubulin agents with antiangiogenic activity as single entities with multitarget chemotherapy potential.ACS medicinal chemistry letters · 2014Article
- Identification of distant drug off-targets by direct superposition of binding pocket surfaces.PloS one · 2013Article
- Preferential selection of isomer binding from chiral mixtures: alternate binding modes observed for the E and Z isomers of a series of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines as ternary complexes with NADPH and human dihydrofolate reductase.Acta crystallographica. Section D, Biological crystallography · 2010Article
- The Z isomer of 2,4-diaminofuro[2,3-d]pyrimidine antifolate promotes unusual crystal packing in a human dihydrofolate reductase ternary complex.Acta crystallographica. Section F, Structural biology and crystallization communications · 2009Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase (DHFR) inhibition, the E- and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal structures (2.0 and 1.4A, respectively) with mouse DHFR and NADPH as well as 1b with human DHFR (1.5A) were determined. The E- and Z-isomers adopt different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3-d]pyrimidines 2-13 were designed and synthesized using the X-ray crystal structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity. Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6-chloromethyl furo[2,3-d]pyrimidine afforded the C8-C9 unsaturated compounds 2-7 and catalytic reduction gave the saturated 8-13. Homologation of the C9-methyl analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and PDGFR-beta were discovered for saturated C9-homologated analogs 9 and 10 that were absent in the saturated C9-methyl analogs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.