634616-77-6

Upstream product

• 296274-32-3 2-chloro-4,5-difluorobenzamide 
• 79-37-8 oxalyl dichloride 

Downstream Products

• 634616-73-2 3-{2-[3-(2-chloro-4,5-difluoro-benzoyl)-ureido]-4-nitro-phenyl}-acrylic acid methyl ester 
• 648927-52-0 1-(5-amino-2-methoxyphenyl)-3-(2-chloro-4,5-difluorobenzoyl)urea 
• 866329-65-9 1-(5-amino-2-chlorophenyl)-3-(2-chloro-4,5-difluorobenzoyl)urea 
• 866329-64-8 1-(2-chloro-5-nitrophenyl)-3-(2-chloro-4,5-difluorobenzoyl)urea 

Relevant academic research and scientific papers

Acyl ureas as human liver glycogen phosphorylase inhibitors for the treatment of type 2 diabetes

Using a focused screening approach, acyl ureas have been discovered as a new class of inhibitors of human liver glycogen phosphorylase (hiGPa). The X-ray structure of screening hit 1 (IC50 = 2 μM) in a complex with rabbit muscle glycogen phosphorylase b reveals that 1 binds at the AMP site, the main allosteric effector site of the dimeric enzyme. A first cycle of chemical optimization supported by X-ray structural data yielded derivative 21, which inhibited hlGPa with an IC50 of 23 ± 1 nM, but showed only moderate cellular activity in isolated rat hepatocytes (IC50 = 6.2 μM). Further optimization was guided by (i) a 3D pharmacophore model that was derived from a training set of 24 compounds and revealed the key chemical features for the biological activity and (ii) the 1.9 A? crystal structure of 21 in complex with hlGPa. A second set of compounds was synthesized and led to 42 with improved cellular activity (hlGPa IC50 = 53 ± 1 nM; hepatocyte IC50 = 380 nM). Administration of 42 to anaesthetized Wistar rats caused a significant reduction of the glucagon-induced hyperglycemic peak. These findings are consistent with the inhibition of hepatic glycogenolysis and support the use of acyl ureas for the treatment of type 2 diabetes.

Acylcarboxylic-4-Carboxyamino phenylureas deriv., its manufacture and its use

The invention relates to acyl-4-carboxyphenylurea derivatives, the physiologically-acceptable salts, physiologically-functional derivatives thereof and compounds of formula (I), where the groups have the given meanings, the physiologically acceptable salt

CARBONYL-AMINO SUBSTITUTED ACYL PHENYL UREA DERIVATIVES, METHOD FOR THE PRODUCTION AND USE THEREOF

The invention relates to compounds of formula (I) wherein the radicals have the cited meaning, in addition to the physiologically compatible salts thereof. The compounds, for example, can be used as medicaments for preventing and treating type 2 diabetes.

UREA-SUBSTITUTED AND URETHANE-SUBSTITUTED ACYLUREAS, METHODS FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICAMENTS

The invention relates to urea-substituted and urethane-substituted acylureas, to physiologically compatible salts thereof and to their physiologically functional derivatives. The invention thus relates to compounds of formula (I), wherein the radicals have the cited meanings. The invention also relates to the physiologically compatible salts of these compounds and to methods for the production thereof. The inventive compounds are suited for use, for example, as antidiabetics.

N-BENZOYLUREIDOCINNAMATE DERIVATIVES, METHOD FOR PRODUCTION AND USE THEREOF

The invention relates to N-benzoylureidocinnamate derivatives of formula (I), where R1-R11 have the meanings given in the claims, the physiologically acceptable salts and method for production thereof. The compounds are suitable as anti-diabetics, for exa