50740-12-0

Upstream product

• 89-86-1 4-hydroxysalicylic acid 
• 51-01-4 2,4-bis(acetyloxy)benzoic acid 

Downstream Products

• 57280-75-8 2',4'-dihydroxy-2-methoxyacetophenone 
• 91398-74-2 2-chloro-1-(2,4-diacetoxy-phenyl)-ethanone 
• 860504-76-3 2,4-dihydroxy-benzoic acid-[2]naphthylamide 
• 114961-99-8 2,5-dihydroxy-benzoic acid dodecylamide 
• 55981-14-1 Acetic acid 5-acetoxy-2-(5-nitro-thiazol-2-ylcarbamoyl)-phenyl ester 

Relevant academic research and scientific papers

Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors

We identified nitazoxanide (NTZ) as a moderate STAT3 pathway inhibitor through immunoblot analysis and a cell-based IL-6/JAK/STAT3 pathway activation assay. A series of thiazolide derivatives were designed and synthesized to further validate the thiazolide scaffold as STAT3 inhibitors. Eight out of 25 derivatives displayed potencies greater than that of NTZ, and their STAT3 pathway inhibitory activities were found to be significantly correlated with their antiproliferative activities in HeLa cells. Derivatives 15 and 24 were observed to be more potent than the positive control WP1066, which is under phase I clinical trials. Compared with NTZ, 15 also exhibited much improved in vivo pharmacokinetic parameters in rats and efficacies against proliferations in multiple cancer cell lines, indicating a broad-spectrum effect of these thiazolides as antitumor agents targeted on STAT3.

S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation

A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5′-chloro-5′-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules.

Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase

Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro.

TETRAHYDROISOQUINOLINE COMPOUNDS AND THEIR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS

A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is H, Cl, F, CH3 or CF3; R2 is H, C1-C6 alkyl or optionally substituted heteroaryl or optionally substituted aryl; and R3 is (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X. The compounds are useful as tetrahydroisoquinoline (THQ) compounds, which are suitable for use as PDK inhibitors, for example for inhibition of cancer cell proliferation.

RESORCINOL N-ARYL AMIDE COMPOUNDS, FOR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS

A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: Y is –CONR1- or optionally substituted arylene or optionally substituted heteroarylene; R1 is H, Cl, F, CH3 or CF3; 10 each R4 is independently H, CH3 or F; R5 is H or CH3; and each R2 and R6 is independently (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X; The compounds of the invention are useful as resorcinol N-aryl amide (NAA) compounds, which are suitable for use as PDK inhibitors, for example for 15 inhibition of cancer cell proliferation.

Biocatalytic Friedel-Crafts alkylation using non-natural cofactors

A novel biocatalytic protocol for C -C bond formation is described and is an equivalent to Friedel-Crafts alkylation. S-Adenosyl-L-methionine (SAM), the major Chemical Equation Presentation methyl donor for biological methylation catalyzed by methyltransferases (Mtases), can perform alkylations (see scheme). These enzymes can accept non-natural cofactors and transfer functionalities other than methyl onto aromatic substrates

Synthesis of selenium-containing polyphenolic acid esters and evaluation of their effects on antioxidation and 5-lipoxygenase inhibition

Six novel selenium-containing polyphenolic acid esters were synthesized and evaluated as antioxidants and 5-lipoxygenase inhibitors. Synthesis of the title compounds involved the Mitsunobu reaction of polyphenolic acids (4-8, 14) with 2-phenylselenoethanol (3). Compounds 22, 23, and 25 were found to be very effective antioxidants and 5-lipoxygenase inhibitors with activity comparable to or better than caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE).

Salicylanilides as inhibitors of the protein tyrosine kinase epidermal growth factor receptor

A pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase and a putative binding mode of 4-anilinoquinazoline suggest that a salicylic acid function could serve as the pharmacophore replacement of a pyrimidine ring. Superpositions by CAMM of salicylanilides with the potent EGFR tyrosine kinase inhibitor 4-[(3′-chlorophenyl)amino]-6,7-dimethoxyquinazoline showed that salicylanilides should act as tyrosine kinase inhibitors. A series of salicylanilides was synthesized and their inhibitory activity against tyrosine kinases determined. Some of them indeed proved to be potent and selective EGFR tyrosine kinase inhibitors. The most potent ones being 28, 16, 20, 6, and 15, with IC50 in the 23-71 nM range.

Novel Enzymatic De-esterification Studies on Substituted Polyacetoxybenzamides

The regioselective capabilities of porcine pancreatic lipase in tetrahydrofuran and Candida rugosa lipase in diisopropyl ether have been investigated for selective deacetylation of peracetates of primary, secondary and tertiary amides of 2-hydroxy-, 2,4-dihydroxy-, 2,5-dihydroxy-, 3,5-dihydroxy- and 3,4,5-trihydroxybenzoic acids. The lipases exhibit random selectivity for the deacetylation of ortho-, meta- and para-acetoxy functions of di/triacetoxybenzamides leading to the formation of the corresponding partially and/or completely deacetylated benzamides. The amide group of all substrates under investigation remains inert to enzymatic hydrolysis. The results of deesterification are in good agreement with our earlier proposed mechanism of action of porcine pancreatic lipase on diaryl or aryl alkyl ketones in organic solvents.