4132-55-2

Upstream product

• 492-21-7 9H-xanthene-9-thione 
• 90-47-1 xanth-9-one 

Downstream Products

• 75996-98-4 N-xanthen-9-ylideneaniline N-oxide 
• 517-45-3 9-(9H-xanthene-9-ylidene)-9H-xanthene 
• 32749-07-8 9-cyclohexylxanthene 
• 96503-12-7 C₂₂H₁₈O 
• 96503-13-8 C₂₂H₁₇⁽²⁾HO 
• 75997-06-7 3'-phenyl-4',4'-dimethylxanthene-9-spiro-2'-oxazolidin-5'-one 
• 121075-71-6 5-trityl-spiro[benzo[1,3]dioxole-2,9'-xanthene] 

Relevant academic research and scientific papers

INHIBITORS OF MTOR-DEPTOR INTERACTIONS AND METHODS OF USE THEREOF

Provided herein are substituted hydrazone compounds useful as inhibitors of DEPTOR. The invention further provides pharmaceutical compositions of the compounds of the invention. The invention also provides medical uses of substituted hydrazone compounds.

Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction

DEPTOR is a 48 kDa protein that binds to mTOR and inhibits this kinase within mTORC1 and mTORC2 complexes. Over-expression of DEPTOR specifically occurs in the multiple myeloma (MM) tumor model and DEPTOR knockdown is cytotoxic to MM cells, suggesting it is a potential therapeutic target. Since mTORC1 paralysis protects MM cells against DEPTOR knockdown, it indicates that the protein–protein interaction between DEPTOR and mTOR is key to MM viability vs death. In a previous study, we used a yeast two-hybrid screen of a small inhibitor library to identify a compound that inhibited DEPTOR/mTOR binding in yeast. This therapeutic (compound B) also prevented DEPTOR/mTOR binding in MM cells and was selectively cytotoxic to MM cells. We now present a structure–activity relationship (SAR) study around this compound as a follow-up report of this previous work. This study has led to the discovery of five new leads – namely compounds 3g, 3k, 4d, 4e and 4g – all of which have anti-myeloma cytotoxic properties superior to compound B. Due to their targeting of DEPTOR, these compounds activate mTORC1 and selectively induce MM cell apoptosis and cell cycle arrest.

Keten. Part 17. Addition Reactions of Ketens with N-Phenyl Nitrones

The N-phenyl nitrones (1a), (4b), and (15) react with ketens in two totally different ways.Triphenylnitrone (4b) forms oxidolones (6) whereas (1a) and (15) form oxazolidinones (2) and (17).The differences appear to be caused by steric interactions in (1a) and (15) which distort the nitrone function and prevent the N-phenyl group adopting the conformation necessary for the oxindole-forming pathway.