185039-89-8

Basic information

• Product Name: 6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one
• Synonyms: 6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one;Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,6-dichlorophenyl)-2-[[4-[2-(diethylaMino)ethoxy]phenyl]aMino]-8-Methyl-;PD0166285
• CAS NO: 185039-89-8
• Molecular Formula: C₂₆H₂₇Cl₂N₅O₂
• Molecular Weight: 512.43088
• EINECS: -0
• Mol File: 185039-89-8.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 665.3±65.0 °C(Predicted)
• Appearance: /
• Density: 1.315±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 9.65±0.25(Predicted)
• CAS DataBase Reference: 6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one(185039-89-8)
• EPA Substance Registry System: 6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one(185039-89-8)

Safety Data

• Hazardous Substances Data: 185039-89-8(Hazardous Substances Data)

Usage

Description

6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one, also known as PD 0166285, is a pyridopyrimidine compound derived from hydrolyzable tannins found in various plant sources. It possesses a unique chemical structure that enables interactions with specific cellular targets, making it a promising pharmaceutical candidate for various applications.

Uses

Used in Pharmaceutical Industry:
PD 0166285 is used as an inhibitor for Wee1, a Ser/Thr kinase that plays a crucial role in regulating the cell cycle. By inhibiting Wee1, PD 0166285 can potentially disrupt the cell cycle, leading to the prevention of uncontrolled cell proliferation and the growth of cancerous cells. This makes it a valuable compound for the development of targeted cancer therapies.
Used in Cancer Research:
PD 0166285 is employed in cancer research as a tool to study the role of Wee1 in the regulation of the cell cycle and its potential as a therapeutic target for various types of cancer. By understanding the molecular mechanisms underlying the action of PD 0166285, researchers can gain insights into the development of novel cancer treatments and the identification of potential biomarkers for cancer diagnosis and prognosis.
Used in Drug Development:
PD 0166285 serves as a lead compound in the development of new drugs targeting Wee1 and related pathways. Its unique chemical structure and biological activity make it an attractive starting point for the design and synthesis of more potent and selective inhibitors, which could potentially lead to the development of more effective cancer therapies with fewer side effects.

Enzyme inhibitor

This potent G2 checkpoint abrogator (FW = 512.43 g/mol; CAS 185039-89- 8; Solubility = 100 mg/mL DMSO), also named 6-(2,6-dichlorophenyl)-2- [[4-[2-(diethylamino)ethoxy]phenyl] amino]-8-methylpyrido[2,3-d] pyrimidin-7(8H)-one, targets Wee1 kinase (IC50 = 24 nM), a enzyme that is crucial for maintaining G2 cell-cycle arrest through its inhibitory phosphorylation of Cdc2. PD-166285 was identified in a screening campaign that was premised on the idea that cells that lack p53 would lack the capacity to engage effective G1 checkpoint regulation, such that they would depend on the G2 checkpoint to permit DNA repair prior to mitosis. This logic led to the hypothesis that a G2 checkpoint abrogator would preferentially kill p53-inactive cancer cells by removing the only checkpoint protecting such cells from premature mitosis in response to DNA damage. At an intracellular concentration of 0.5 μM, PD0166285 potently inhibits irradiation-induced Cdc2 phosphorylation at Tyr-15 and Thr-14 in seven of seven cancer cell lines tested, showing that this G2 checkpoint abrogator can kill cancer cells. Notably, PD0166285 is a radiosensitizer, enhancing cell sensitivity to radiation-induced cell death, showing a sensitivity enhancement ratio of 1.23 in a standard clonogenic assay. Its radiosensitizing activity is p53-dependent, showing a higher efficacy in p53-inactive cells. Treatment of B16 mouse melanoma cells with the inhibitor B16 cells also dramatically abrogates the G2 checkpoint, with arrest in the early G1 phase at 0.5 muM for 4 hours observed by flow cytometry. Cyclin D mRNA decreased within 4 hours observed by Realtime PCR. Rb was dephosphrylated for 24 hours. However, B16 cells did not undergo cell death after treatment with 0.5 μM PD0166285 for 24 hours. Immnofluoscence microscopy also showed that the cells become round and small in the morphogenesis, suggesting that microtubule stabilization is blocked and that Wee1 distribution was restricted after treatment for 4 hours. PD0166285 also abrogates the G2 checkpoint in osteosarcoma (OS) cells, pushing them into mitotic catastrophe and sensitizing them to irradiation-induced cell death. Other agents, like caffeine and UCN-01, can also abrogate the G2 checkpoint, thereby sensitizing p53 inactive cells to apoptosis. Other Targets: Myelin transcription factor-1, or Myt1 (IC50 = 72 nM); checkpoint kinase Chk1 IC50 = 3.4 μM)

Upstream product

• 185040-32-8 4-methylamino-2-methylthiopyrimidine-5-carboxaldehyde 
• 185039-37-6 N-[6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-ylidene]-acetamide 
• 185039-29-6 6-(2,6-Dichlorophenyl)-8-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]-pyrimidin-7-ylideneamine 
• 185039-46-7 6-(2,6-dichlorophenyl)-8-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 76360-82-2 4-methylamino-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester 
• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 
• 17759-30-7 (4-methylamino-2-methylsulfanyl-pyrimidin-5-yl)-methanol 
• 38519-63-0 4-[2-(diethylamino)ethoxy]aniline 
• 185039-48-9 6-(2,6-dichlorophenyl)-8-methyl-2-(methylsulfonyl)pyrido[2,3-d]pyrimidin-7(8H)-one 

Downstream Products

• 1245555-34-3 2-(4-{[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}phenoxy)-N,N-diethyl-N-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]ethanammonium bromide 

Relevant articles and documents

Preparation of pyrido[2,3-d]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation.

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