1000339-35-4

Upstream product

• 23095-05-8 5-bromo-2-methoxybenzenesulfonyl chloride 
• 765-30-0 Cyclopropylamine 
• 104-92-7 1-bromo-4-methoxy-benzene 

Downstream Products

• 1355554-26-5 N-cyclopropyl-5-(3,5-dimethyl-4-isoxazolyl)-2-(methyloxy)benzenesulfonamide 
• 1443151-92-5 N-cyclopropyl-5(4-[[2-(4-fluorophenyl)ethyl]amino]-6-methoxy-1,3,5-triazin-2-yl)-2-methoxybenzenesulfonamide 

Relevant academic research and scientific papers

1,3,5-TRIAZINE-2-AMINE DERIVATIVES, PREPARATION THEREOF AND DIAGNOSTIC AND THERAPEUTIC USE THEREOF

The present invention relates to compounds corresponding to formula (I) in which: - R1 represents a substituted phenyl; - R2 represents: - a substituted phenyl; - a heteroaromatic group, the said group being unsubstituted or substituted one or more times; - R3 represents a group Alk; - R4 represents a hydrogen atom or a (C1-C4)alkyl; - R5 represents a hydrogen atom, a (C3-C6)cycloalkyl or a (C1-C4)alkyl-O-Alk; - or alternatively R4 and R5, together with the nitrogen atom to which they are attached, constitute a heterocyclic radical chosen from: azetidin-1-yl, pyrrolidin-1-yl, piperid-1-yl, morpholin-4-yl; - R6 represents a group -COOAlk, a group -CONH2 or a group -NHSO2 Alk; - Alk represents a (C1-C4)alkyl, which is unsubstituted or substituted one or more times with a halogen atom; in the form of the base or of an acid-addition salt. Preparation process and diagnostic and therapeutic use

Fragment-based discovery of bromodomain inhibitors part 2: Optimization of phenylisoxazole sulfonamides

Bromodomains are epigenetic reader modules that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Inhibitors of this protein-protein interaction have the potential to modulate multiple diseases as demonstrated by the profound anti-inflammatory and antiproliferative effects of a recently disclosed class of BET compounds. While these compounds were discovered using phenotypic assays, here we present a highly efficient alternative approach to find new chemical templates, exploiting the abundant structural knowledge that exists for this target class. A phenyl dimethyl isoxazole chemotype resulting from a focused fragment screen has been rapidly optimized through structure-based design, leading to a sulfonamide series showing anti-inflammatory activity in cellular assays. This proof-of-principle experiment demonstrates the tractability of the BET family and bromodomain target class to fragment-based hit discovery and structure-based lead optimization.