1226548-39-5

Basic information

• Product Name: S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol
• Synonyms: S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol
• CAS NO: 1226548-39-5
• Molecular Weight: 407.472
• Mol File: 1226548-39-5.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol(CAS DataBase Reference)
• NIST Chemistry Reference: S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol(1226548-39-5)
• EPA Substance Registry System: S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol(1226548-39-5)

Safety Data

• Hazardous Substances Data: 1226548-39-5(Hazardous Substances Data)

Upstream product

• 65148-07-4 4-chloro-5,6-diphenylfuro[2,3-d]pyrimidine 
• 20989-17-7 (2S)-2-phenylglycinol 

Relevant articles and documents

Protein kinase inhibitor design by targeting the Asp-Phe-Gly (DFG) motif: The role of the DFG motif in the design of epidermal growth factor receptor inhibitors

The Asp-Phe-Gly (DFG) motif plays an important role in the regulation of kinase activity. Structure-based drug design was performed to design compounds able to interact with the DFG motif; epidermal growth factor receptor (EGFR) was selected as an example. Structural insights obtained from the EGFR/2a complex suggested that an extension from the meta-position on the phenyl group (ring-5) would improve interactions with the DFG motif. Indeed, introduction of an N,N-dimethylamino tail resulted in 4b, which showed almost 50-fold improvement in inhibition compared to 2a. Structural studies confirmed this N,N-dimethylamino tail moved toward the DFG motif to form a salt bridge with the side chain of Asp831. That the interactions with the DFG motif greatly contribute to the potency of 4b is strongly evidenced by synthesizing and testing compounds 2a, 3g, and 4f: when the charge interactions are absent, the inhibitory activity decreased significantly.

Fast-forwarding hit to lead: Aurora and epidermal growth factor receptor kinase inhibitor lead identification

A focused library of furanopyrimidine (350 compounds) was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit 1a was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity in HCT-116 colon cancer cell line. On the basis of docking studies with EGFR hit 1s, introduction of acrylamide Michael acceptor group led to 8, which inhibited both the wild and mutant EGFR kinase and also showed antiproliferative activity in HCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.