Dactolisib

Base Information

• Chemical Name: Dactolisib
• CAS No.: 915019-65-7
• Deprecated CAS: 1146702-52-4
• Molecular Formula: C₃₀H₂₃N₅O
• Molecular Weight: 469.546
• NSC Number: 751249
• UNII: RUJ6Z9Y0DT
• DSSTox Substance ID: DTXSID10238599
• Nikkaji Number: J2.731.431G
• Wikipedia: Dactolisib
• Wikidata: Q4835503
• NCI Thesaurus Code: C74072
• Pharos Ligand ID: P3TVMWNWJR6K
• Metabolomics Workbench ID: 65874
• ChEMBL ID: CHEMBL1879463
• Mol file: 915019-65-7.mol

Synonyms:2-methyl-2-(4-(3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydroimidazo(4,5-c)quinolin-1-yl)phenyl)propanenitrile;2-methyl-2-(4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-1h-imidazo(4,5-c)quinolin-1-yl)phenyl)propanenitrile;BEZ235;dactolisib;NVP BEZ235;NVP-BEZ235;NVPBEZ235

Chemical Property of Dactolisib

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 288-289°C
• Refractive Index: 1.705
• Boiling Point: 701.025 °C at 760 mmHg
• PKA: 6.41±0.20(Predicted)
• Flash Point: 377.767 °C
• PSA: 76.50000
• Density: 1.299 g/cm³
• LogP: 4.36208
• Storage Temp.: Refrigerator
• Solubility.: Soluble in DMSO (up to 1 mg/ml with warming) or in DMF (up to 10 mg/ml, dissolves slowly, requires heating to 75?C).
• XLogP3: 5.2
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 469.19026037
• Heavy Atom Count: 36
• Complexity: 872

Purity/Quality:

99% ^*data from raw suppliers

NVP-BEZ 235 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(C#N)C1=CC=C(C=C1)N2C3=C4C=C(C=CC4=NC=C3N(C2=O)C)C5=CC6=CC=CC=C6N=C5
• Recent ClinicalTrials: A Phase I, Dose-finding Study of BEZ235 in Adult Patients With Relapsed or Refractory Acute Leukemia
• Recent EU Clinical Trials: A Multicenter, Randomized, Double Blind, Placebo-Controlled, Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly
• Description: NVP-BEZ235 (915019-65-7) is a dual PI3K and mTOR kinase inhibitor.1?It inhibits VEGF-induced proliferation and angiogenesis.2?Reverses lapatinib resistance.3?It induces G1 arrest and reduces cyclin D1 expression in melanoma cells with negligible apoptosis.4?NVP-BEZ235 inhibits the growth of cancer cells with activating PI3K mutations.5?The ability of NVP-BEZ235 to inhibit PI3K has come into question. This study also shows it to be a potent inhibitor of PRKDC (IC50 = 29 nM), ATM (IC50 = 13 nM), and ATR (IC50 = 8 nM).6?Active in vivo.
• Uses: Inhibitor of phosphatidylinositol 3-kinases, P13K and mTOR. Phosphatidylinositol 3-kinase (PI3K) signaling through Akt/PKB and the mammalian target of rapamycin (mTOR) controls gene expression related to cell proliferation, differentiation, and apoptosis. Increased activity of this pathway is important in many types of cancer. NVP-BEZ235 is a potent dual inhibitor of PI3K and mTOR that is well tolerated, displays disease stasis when administered orally, and enhances the efficacy of other anticancer agents when used in in vivo combination studies. It inhibits PI3K isoforms and mutants with low nanomolar IC50 values, leading to growth arrest in the G1 phase. Through its effects on PI3K, NVP-BEZ235 inhibits VEGF-induced angiogenesis. By directly blocking cell growth and indirectly inhibiting angiogenesis, it has potential in both solid tumors and in metastatic melanoma therapy.[Cayman Chemical]

Technology Process of Dactolisib

There total 14 articles about Dactolisib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 88.0%

2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile (915019-50-0) + quinolin-3-ylboronic acid (191162-39-7) → 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile (915019-65-7)

Guidance literature:

With bis-triphenylphosphine-palladium(II) chloride; potassium hydrogencarbonate; triphenylphosphine; In water; N,N-dimethyl-formamide; at 95 - 100 ℃; Reagent/catalyst; Solvent; Inert atmosphere; Large scale;

DOI:10.1021/acs.oprd.9b00221

Reference yield:

6-bromo-4-chloro-3-nitroquinoline (723281-72-9) → 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile (915019-65-7)

Guidance literature:

Multi-step reaction with 5 steps

1: acetic acid / 2 h

2: hydrogen / tetrahydrofuran; methanol / 1 h / 825.08 Torr

3: triethylamine / dichloromethane / 1 h / 0 °C

4: tetrabutylammomium bromide; sodium hydroxide / water; dichloromethane / 72 h / 20 °C

5: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / N,N-dimethyl-formamide / 1 h / 100 °C

With bis-triphenylphosphine-palladium(II) chloride; tetrabutylammomium bromide; hydrogen; sodium carbonate; acetic acid; triethylamine; sodium hydroxide; In tetrahydrofuran; methanol; dichloromethane; water; N,N-dimethyl-formamide;

Reference yield:

2-[4-(3-amino-6-bromo-quinolin-4-ylamino)-phenyl]-2-methyl-propionitrile (915019-52-2) → 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile (915019-65-7)

Guidance literature:

Multi-step reaction with 3 steps

1: triethylamine / dichloromethane / 1 h / 0 °C

2: tetrabutylammomium bromide; sodium hydroxide / water; dichloromethane / 72 h / 20 °C

3: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / N,N-dimethyl-formamide / 1 h / 100 °C

With bis-triphenylphosphine-palladium(II) chloride; tetrabutylammomium bromide; sodium carbonate; triethylamine; sodium hydroxide; In dichloromethane; water; N,N-dimethyl-formamide;

upstream raw materials:

2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile

quinolin-3-ylboronic acid

6-bromo-3-nitroquinolin-4-ol

6-bromo-4-chloro-3-nitroquinoline

Refernces

• 1、 Lu, Xiao,Kim, Myunghoon,Orr, Meghan J.,Li, Hao,Huang, Wenwei. "Acid-Promoted Cascade Reaction of N-(4-Chloroquinolin-3-yl)carbamates with Amines: One-Pot Assembly of Imidazo[4,5-c]quinolin-2-ones". supporting information. p. 1572 - 1580. Retrieved 2018/04/20.
• 2、 -. "JAK PI3K/mTOR combination therapy". Page/Page column 21; 22. . Retrieved 2016/06/28.