1001917-37-8

Basic information

• Product Name: 3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide
• Synonyms: 3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide;MK-8033;1-(3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(pyridin-2-ylmethyl)methanesulfonamide;3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinyLMethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin
• CAS NO: 1001917-37-8
• Molecular Formula: C25H21N5O3S
• Molecular Weight: 471.53094
• Mol File: 1001917-37-8.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 761.011 °C at 760 mmHg
• Flash Point: 414.045 °C
• Appearance: /
• Density: 1.39
• PKA: 8.93±0.40(Predicted)
• CAS DataBase Reference: 3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide(1001917-37-8)
• EPA Substance Registry System: 3-(1-Methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide(1001917-37-8)

Safety Data

• Hazardous Substances Data: 1001917-37-8(Hazardous Substances Data)

Usage

Uses

MK 8033 is a novel and specific dual ATP competitive c-Met/Ron inhibitor and is used in the treatment of cancer.

Upstream product

• 1001917-35-6 1-(3-chloro-5-oxo-5Hbenzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-(pyridin-2-ylmethyl)methanesulfonamide 
• 761446-44-0 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 

Relevant articles and documents

Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5] cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): A specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c-Met

This report documents the first example of a specific inhibitor of protein kinases with preferential binding to the activated kinase conformation: 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one 11r (MK-8033), a dual c-Met/Ron inhibitor under investigation as a treatment for cancer. The design of 11r was based on the desire to reduce time-dependent inhibition of CYP3A4 (TDI) by members of this structural class. A novel two-step protocol for the synthesis of benzylic sulfonamides was developed to access 11r and analogues. We provide a rationale for the observed selectivity based on X-ray crystallographic evidence and discuss selectivity trends with additional examples. Importantly, 11r provides full inhibition of tumor growth in a c-Met amplified (GTL-16) subcutaneous tumor xenograft model and may have an advantage over inactive form kinase inhibitors due to equal potency against a panel of oncogenic activating mutations of c-Met in contrast to c-Met inhibitors without preferential binding to the active kinase conformation.