307308-63-0

Upstream product

• 103859-67-2 1-iodo-2-(4-nitrophenoxy)benzene 
• 34883-46-0 1-(2-iodophenoxy)benzene 
• 26196-58-7 2-(4-aminophenoxy)-1-nitrobenzene 
• 30202-85-8 2,4'-diaminodiphenyl ether 
• 1493-27-2 ortho-nitrofluorobenzene 
• 123-30-8 4-amino-phenol 

Relevant academic research and scientific papers

Structure-Based Optimization of 3-Phenyl-N-(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors

Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpression. Based on previously discovered compounds with a 3-phenylthiophene-2-sulfonamide core moiety, in this work, we have obtained new compounds with improved binding affinity and/or selectivity under the guidance of structure-based design. The most potent compounds achieved sub-micromolar binding affinities to Mcl-1 (Ki～ 0.4 μM) and good cytotoxicity (IC5015N-heteronuclear single-quantum coherence NMR spectra suggested that these compounds bound to the BH3-binding groove on Mcl-1. Several cellular assays revealed that FWJ-D4 as well as its precursor FWJ-D5 effectively induced caspase-dependent apoptosis, and their target engagement at Mcl-1 was confirmed by co-immunoprecipitation experiments. Treatment with FWJ-D5 at 50 mg/kg every 2 days on an RS4;11 xenograft mouse model for 22 days led to 75% reduction in tumor volume without body weight loss.

Derivatives of quinoline as inhibitors for MEK

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof. wherein: n is 0-1; X and Y are independently selected from -NH-, -O-, -S-, or -NR8- where R8 is alkyl of 1-6 carbon atoms and X may additionally comprise a CH2 group; R7 is a group (CH2)mR9 where m is 0,or an integer of from 1-3 and R9 is a substituted aryl group, an optionally substituted cycloalkyl ring of up to 10 carbon atoms, or an optionally substituted heterocyclic ring or an N-oxide of any nitrogen containing ring; R6 is a divalent cycloalkyl of 3 to 7 carbon atoms, which may be optionally further substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a divalent pyridinyl, pyimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally further substituted with one or more specified groups; R1, R2, R3 and R4 are each independently selected from hydrogen or various specified organic groups. Compounds are useful as pharmaceuticals for the inhibition of MEK activity.