1370974-73-4

Upstream product

• 4959-60-8 4,5-dimethoxy-2-nitrobenzamide 
• 29568-78-3 4,5-dimethoxy-2-nitrobenzoyl chloride 
• 4998-07-6 4,5-dimethoxy-2-nitro-benzoic acid 
• 5004-88-6 4,5-dimethoxyanthranilamide 
• 14002-51-8 4-biphenyl-carboxylic acid chloride 
• 42498-44-2 3-phenylbenzoyl chloride 

Downstream Products

• 911418-10-5 2-[(3-phenyl)phenyl]-6,7-dimethoxyquinazolin-4(3H)-one 
• 911418-21-8 tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl]-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911418-16-1 tert-butyl 5-(6-(2-tert-butoxy-2-oxoethoxy)-2-[(3-phenyl)phenyl]-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911418-25-2 tert-butyl 5-(2-[(3-phenyl)phenyl]-7-methoxy-6-(2-(4-methylpiperazin-1-yl)ethoxy)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 

Relevant academic research and scientific papers

Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action

Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1’-biphenyl-4-carboxamides 14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives 13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562?cells. Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative 17b showed a better antitumoral effect on K562?cells than 13b and 14b. Analyses performed to explore 17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequent to DNA lesions as demonstrated by the increase in phospho-ATM and γH2AX, two known markers of DNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK and induction of caspase-3 dependent apoptosis.

PHARMACOKINETICALLY IMPROVED COMPOUNDS

The present invention relates to inhibitors of ROCKl and R0CK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCKl and or R0CK2 that are useful for the treatment of disease.