195155-27-2

Upstream product

• 109-01-3 1-methyl-piperazine 
• 85822-16-8 4-formylbenzene-1-sulfonyl chloride 
• 13736-22-6 sodium 4-carboxy-benzenesulfonate 

Downstream Products

• 1080675-28-0 (E)-1-(4-chloro-2-nitro-phenyl)-3-[4-(4-methylpiperazine-1-sulfonyl)phenyl]propenone 
• 862499-61-4 N-(tert-butyl)-C-[4-(4-methyl-piperazine-1-sulfonyl)phenyl]nitrone 

Relevant academic research and scientific papers

An Exploration of Chemical Properties Required for Cooperative Stabilization of the 14-3-3 Interaction with NF-κB—Utilizing a Reversible Covalent Tethering Approach

Protein-protein modulation has emerged as a proven approach to drug discovery. While significant progress has been gained in developing protein-protein interaction (PPI) inhibitors, the orthogonal approach of PPI stabilization lacks established methodologies for drug design. Here, we report the systematic ″bottom-up″ development of a reversible covalent PPI stabilizer. An imine bond was employed to anchor the stabilizer at the interface of the 14-3-3/p65 complex, leading to a molecular glue that elicited an 81-fold increase in complex stabilization. Utilizing protein crystallography and biophysical assays, we deconvoluted how chemical properties of a stabilizer translate to structural changes in the ternary 14-3-3/p65/molecular glue complex. Furthermore, we explore how this leads to high cooperativity and increased stability of the complex.

Dihydroquinone and dihydronaphthridine inhibitors of JNK

Compounds of formula I are effective modulators of JNK: wherein X is CR11 or N;Y is —C(O)R3, 5-membered heteroaryl, or 5-membered heterocyclyl;Z is phenyl, cycloalkyl, heterocyclyl or heteroaryl, and is substituted with R1 and R2;R1 and R2 are each independently H, halo, CN, lower alkyl, or —Y1—Y2—Y3—R8, or R1 and R2 together form —O(CH2)nO—, where n is 1 or 2; Y1 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —S—, —SO2—, or a bond;Y2 is cycloalkylene, heterocycloalkylene, lower alkylene or a bond;Y3 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —SO2—, or a bond;R8 is H, lower alkyl, lower alkoxy, cycloalkyl, heterocycloalkyl, or —NR9R10, wherein R8 other than H is optionally substituted with lower alkyl, halo, —CF3, or —OH; R9 and R10 are each independently H or lower alkyl;R3 is OH, lower alkyl, lower alkoxy, (lower alkoxy)-lower alkoxy, or —NR9R10;R4 is lower alkyl, phenyl, heterocyclyl, cycloalkyl, heterocycloalkyl, or heteroaryl, and is optionally substituted with lower alkyl, hydroxy, lower alkoxy, halo, nitro, amino, cyano, or halo-lower alkyl;R5 and R6 are each independently H, halo, cyano, lower alkyl, —CF3, lower alkoxy, —OCHF2, —NO2, or —NR9R10;R7 is H, F, Cl, methyl, or OH;R11 is H, lower alkyl, lower cycloalkyl, or phenyl;or a pharmaceutically acceptable salt thereof.