143328-29-4

Upstream product

• 1878-68-8 2-(4-bromophenyl)-acetic acid 
• 41841-16-1 (4-bromo-phenyl)-acetic acid methyl ester 
• 143328-19-2 1-(4-bromophenyl)cyclopentane-1-carbonitrile 
• 143328-24-9 1-(4-bromophenyl)cyclopentanecarboxylic acid 
• 16532-79-9 4-Bromophenylacetonitrile 

Downstream Products

• 143433-72-1 Sodium; (6R,7R)-3-acetoxymethyl-7-{[1-(4-bromo-phenyl)-cyclopentanecarbonyl]-amino}-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate 
• 143407-71-0 Sodium; (2S,5R,6R)-6-{[1-(4-bromo-phenyl)-cyclopentanecarbonyl]-amino}-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate 
• 143407-75-4 Sodium; (6R,7R)-7-{[1-(4-bromo-phenyl)-cyclopentanecarbonyl]-amino}-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate 

Relevant academic research and scientific papers

Palladium(II)-Catalyzed C(sp2)-H Bond Activation/C-N Bond Cleavage Annulation of N-Methoxy Amides and Arynes

The Pd(II)-catalyzed C-H bond activation/C-N bond cleavage annulation reaction of N-alkyoxyamide aryne is developed to synthesize 9,10-dihydrophenanthrenone derivatives. This reaction exhibited good functional group compatibility with yields up to 92%. Detailed mechanistic studies showed that the key to C-N bond cleavage is the formed eight-membered palladacycle intermediate undergoing nucleophilic addition to the carbonyl group, which provides a new and practical way for N-alkoxyamide directed C-H bond activation.

Amide compound and derivative thereof, preparation method, pharmaceutical composition and application thereof

The invention discloses an amide compound and derivative thereof, a preparation method, a pharmaceutical composition and application thereof. The structure of the amide compound is shown as a formula (I). The derivatives of theamide compound relate to a stereoisomer, a tautomer, a metabolite, a metabolic precursor, a prodrug, a solvate, a salt of the solvate, a crystal, a pharmaceutically acceptable salt or a mixture of the above of theamide compound. The amide compound and the derivative thereof have an efficient inhibition effect on indoleamine 2, 3-dioxygenase 1, and can be used for preparing medicines for treating indoleamine 2, 3-dioxygenase 1 mediated immunosuppression related diseases, the prepared medicine can exert the medicine effect at the molecular level and is wide in application, and the synthesis method of the compound is simple, convenient and easy to operate.

Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.