887578-70-3

Basic information

• Product Name: 2-BROMOISONICOTINOYL CHLORIDE
• Synonyms: 2-BROMOISONICOTINOYL CHLORIDE;4-PYRIDINECARBONYL CHLORIDE, 2-BROMO-;2-BROMOISONICOTINO
• CAS NO: 887578-70-3
• Molecular Formula: C6H3BrClNO
• Molecular Weight: 220.45
• Mol File: 887578-70-3.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 2-BROMOISONICOTINOYL CHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-BROMOISONICOTINOYL CHLORIDE(887578-70-3)
• EPA Substance Registry System: 2-BROMOISONICOTINOYL CHLORIDE(887578-70-3)

Safety Data

• Hazardous Substances Data: 887578-70-3(Hazardous Substances Data)

Upstream product

• 66572-56-3 2-bromoisonicotinic acid 

Relevant articles and documents

Evaluation of carbon-11 labeled 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide as PET tracer for imaging of CSF-1R expression in the brain

Pharmacological targeting of tumor associated macrophages and microglia in the tumor microenvironment is a novel therapeutic strategy in the treatment of glioblastoma multiforme. As such, the colony stimulating factor-1 receptor (CSF-1R) has been identified as a druggable target. However, no validated companion diagnostic marker for these therapies exists to date. Towards development of a CSF-1R PET tracer, a set of six compounds based on recently reported CSF-1R inhibitor 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide (Compound 5) was designed, synthesized and evaluated in vitro for potency and selectivity. The highest affinity for CSF-1R was found for compound 5 (IC50: 2.7 nM). Subsequent radiosynthesis of [11C]5 was achieved in 2.0 ± 0.2% yield (decay corrected to start of synthesis) by carbon-11 carbon monoxide aminocarbonylation in 40 min after end of bombardment. In vitro autoradiography with [11C]5 on rat brain sections demonstrated high specific binding, but also strong off-target binding. Ex vivo, only intact tracer was observed in blood plasma at 90 min post injection in healthy rats. PET scanning results demonstrated negligible brain uptake under baseline conditions and this brain uptake did not increase by blocking of efflux transporters using Tariquidar. To conclude, [11C]5 was successfully synthesized and evaluated in healthy rats. However, the inability of [11C]5 to cross the blood-brain-barrier excludes its use for imaging of CSF-1R expression in the brain.

Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors

FGF receptors (FGFRs) are tyrosine kinases that are overexpressed in diverse tumors by genetic alterations such as gene amplifications, somatic mutations and translocations. Owing to this characteristic, FGFRs are attractive targets for cancer treatment. It has been demonstrated that most multi-targeted, ATP competitive tyrosine kinase inhibitors are active against FGFRs as well as other kinases. The design of new and more selective inhibitors of FGFRs, which might be reduced off-target and side effects, is a difficult yet significant challenge. The results of the current investigation, show that novel Ponatinib analogues are highly active as FGFR inhibitors and that they possess reduced kinase insert domain receptor (KDR) activities. Observations made in a structure and activity relationship (SAR) investigation led to the development of a promising, orally available lead compound 4, which displays a 50–100 fold in vitro selectivity for inhibition of FGFR1-3 over KDR. In addition, biological evaluation of compound 4 showed that it displays significant antitumor activities in FGFR1-amplificated H1581 and FGFR2-amplificated SNU-16 xenograft models.

Monocyclic heterocycles as kinase inhibitors

The present invention is directed to compounds having the formula and methods for using them for the treatment of cancer.