1152131-83-3

Upstream product

• 6723-30-4 O-2-tetrahydro-2H-pyranhydroxylamine 
• 1152131-79-7 3-[5-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}furan-2-yl]acrylic acid 
• 443882-99-3 3-chloro-4-(3-fluorobenzyloxy)nitrobenzene 
• 16064-08-7 6-iodo-1H-quinazolin-4-one 
• 1257665-55-6 3-[5-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}furan-2-yl]acrylic acid tert-butyl ester 
• 98556-31-1 4-chloro-6-iodoquinazoline 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 456-47-3 3-fluoro-benzenemethanol 
• 5326-47-6 2-amino-5-iodobenzoic acid 
• 231278-20-9 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodoquinazolin-4-amine 
• 231278-84-5 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde 
• 202197-26-0 3-chloro-4-(3-fluorobenzyloxy)aniline 

Downstream Products

• 1152131-95-7 3-[5-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}furan-2-yl]-N-hydroxyacrylamide hydrochloride 

Relevant academic research and scientific papers

Novel chimeric histone deacetylase inhibitors: A series of lapatinib hybrides as potent inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and histone deacetylase activity

Reversible lysine-specific acetylation has been described as an important posttranslational modification, regulating chromatin structure and transcriptional activity in the case of core histone proteins. Histone deacetylases (HDAC) are considered as a promising target for anticancer drug development, with 2a as pan-HDAC inhibitor approved for cutanous T-cell lymphoma therapy and several other HDAC inhibitors currently in preclinical and clinical development. Protein kinases are a well-established target for cancer therapy with the EGFR/HER2 inhibitor 5 approved for treatment of advanced, HER2 positive breast cancer as a prominent example. In the present report, we present a novel strategy for cancer drug development by combination of EGFR/HER2 kinase and HDAC inhibitory activity in one molecule. By combining the structural features of 5 with an (E)-3-(aryl)-N-hydroxyacrylamide motif known from HDAC inhibitors like 1 or 3, we obtained selective inhibitors for both targets with potent cellular activity (target inhibition and cytotoxicity) of selected compounds 6a and 6c. By combining two distinct pharmacologically properties in one molecule, we postulate a broader activity spectrum and less likelihood of drug resistance in cancer patients.

NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES

The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth