21561-09-1

Basic information

• Product Name: 4-PHENYLAMINO-6,7-DIMETHOXYQUINAZOLINE
• Synonyms: WHI-P258;N-(6,7-DIMETHOXY-4-QUINAZOLINYL)-N-PHENYLAMINE;JAK3 INHIBITOR, NEGATIVE CONTROL;4-PHENYLAMINO-6,7-DIMETHOXYQUINAZOLINE;6,7-DIMETHOXY-N-PHENYL-4-QUINAZOLINAMINE;6,7-dimethoxy-N-phenylquinazolin-4-amine;4-Quinazolinamine, 6,7-dimethoxy-N-phenyl-
• CAS NO: 21561-09-1
• Molecular Formula: C₁₆H₁₅N₃O₂
• Molecular Weight: 281.31
• Product Categories: Inhibitors
• Mol File: 21561-09-1.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 441.2±40.0 °C(Predicted)
• Appearance: /
• Density: 1 +-.0.06 g/cm3(Predicted)
• PKA: 6.19±0.70(Predicted)
• CAS DataBase Reference: 4-PHENYLAMINO-6,7-DIMETHOXYQUINAZOLINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-PHENYLAMINO-6,7-DIMETHOXYQUINAZOLINE(21561-09-1)
• EPA Substance Registry System: 4-PHENYLAMINO-6,7-DIMETHOXYQUINAZOLINE(21561-09-1)

Safety Data

• Hazardous Substances Data: 21561-09-1(Hazardous Substances Data)

Usage

Description

4-Phenylamino-6,7-dimethoxyquinazoline, also known as WHI-P258, is a quinazoline compound that has been studied for its potential interactions with Janus kinase 3 (JAK3). Modeling studies suggested that it would bind to the active site of JAK3 with an estimated Ki value of 72 μM. However, it has been found to be inactive at JAK3 (IC50 = >300 μM) and is often used as a negative control for structurally similar compounds.

Uses

Used in Pharmaceutical Research:
4-Phenylamino-6,7-dimethoxyquinazoline is used as a specific inhibitor of Janus kinase 3 (JAK3) for studying the role of JAK3 in various biological processes and diseases. Its inactive nature at JAK3 makes it a valuable negative control in experiments involving structurally similar compounds that inhibit platelet aggregation and herpes simplex virus 1 (HSV-1) replication.
Used in Drug Development:
In the drug development industry, 4-Phenylamino-6,7-dimethoxyquinazoline serves as a reference compound for the design and synthesis of more potent and selective JAK3 inhibitors. Its structural characteristics can be used to guide the development of new compounds with improved binding affinity and efficacy against JAK3, which may have potential therapeutic applications in treating diseases associated with JAK3 dysregulation.

Upstream product

• 62-53-3 aniline 
• 13790-39-1 6,7-dimethoxy-4-chloroquinazoline 
• 13794-72-4 3H-6,7-dimethoxyquinazolin-4-one 
• 5653-40-7 2-Amino-4,5-dimethoxybenzoic acid 

Relevant articles and documents

Antiproliferative efficacy of n-(3-chloro-4-fluorophenyl)-6, 7-dimethoxyquinazolin-4-amine, dw-8, in colon cancer cells is mediated by intrinsic apoptosis

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 μM, 5.80 ± 0.92 μM, and 6.15 ± 0.37 μM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 μM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 μM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

Virtual Screening Identifies Irreversible FMS-like Tyrosine Kinase 3 Inhibitors with Activity toward Resistance-Conferring Mutations

The use of covalent irreversible binding inhibitors is an established concept for drug development. Usually, the discovery of new irreversible kinase inhibitors occurs serendipitously, showing that efficient rational approaches for the rapid discovery of new drugs are needed. Herein, we report a virtual screening strategy that led to the discovery of irreversible inhibitors of FMS-like tyrosine kinase 3 (FLT3) involved in the pathogenesis of acute myeloid leukemia. A virtual screening library was designed to target the highly conserved Cys828 residue preceding the DFG motif by modification of reported reversible inhibitors with chemically reactive groups. Prospective covalent docking allowed the identification of two lead series, resulting in a massive increase in inhibition of kinase activity and cell viability by irreversible inhibitors compared to the corresponding reversible scaffolds. Lead compound 4b (BSc5371) displays superior cytotoxicity in FLT3-dependent cell lines to compounds in recent clinical trials and overcomes drug-resistant mutations.

Anilinoquinazoline inhibitors of the RET kinase domain - Elaboration of the 7-position

We have previously reported a series of anilinoquinazoline derivatives as potent and selective biochemical inhibitors of the RET kinase domain. However, these derivatives displayed diminished cellular potency. Herein we describe further optimisation of the series through modification of their physicochemical properties, delivering improvements in cell potency. However, whilst cellular selectivity against key targets could be maintained, combining cell potency and acceptable pharmacokinetics proved challenging.