22568-87-2

Upstream product

• 117-99-7 2-Hydroxybenzophenone 
• 106-89-8 epichlorohydrin 

Downstream Products

• 137503-81-2 {2-[(S)-3-(2-Benzoyl-phenoxy)-2-hydroxy-propylamino]-5-chloro-phenyl}-phenyl-methanone 
• 137503-91-4 {2-[(R)-3-(2-Benzoyl-phenoxy)-2-hydroxy-propylamino]-5-chloro-phenyl}-phenyl-methanone 
• 143328-78-3 {2-[(R)-3-(2-Benzoyl-phenylamino)-2-hydroxy-propoxy]-phenyl}-phenyl-methanone 
• 143328-70-5 {2-[(S)-3-(2-Benzoyl-phenylamino)-2-hydroxy-propoxy]-phenyl}-phenyl-methanone 
• 54915-35-4 2-<3-(3,4-Dimethoxyphenylethylamino)-2-hydroxypropoxy>benzophenon 
• 441348-53-4 B₅₉ 
• 1370320-77-6 [2-(2-hydroxy-3-morpholine-4-ylpropoxy)phenyl]phenylmethanone 
• 1370320-72-1 [2-(2-hydroxy-3-piperazine-1-ylpropoxy)phenyl]phenylmethanone 
• 1370320-81-2 [2-(3-{4-[3-(2-benzoylphenoxy)-2-hydroxylpropyl]piperazine-1-yl}-2-hydroxypropoxy)phenyl]phenylmethanone 
• 1370320-82-3 1-[2-(3-{4-[3-(2-benzoylphenoxy)-2-hydroxylpropyl]piperazine-1-yl}-2-hydroxypropoxy)-5-methylphenyl]ethanone 
• 1370320-79-8 4-[3-(2-benzoylphenoxy)-2-hydroxypropyl]piperazine-1-carboxylic acid p-tolylamide 
• 1370320-80-1 4-[3-(2-benzoylphenoxy)-2-hydroxypropyl]piperazine-1-carbothioic acid p-tolylamide 
• 1370320-73-2 (2-{3-[4-(2,3-xylyl)piperazine-1-yl]-2-hydroxypropoxy}phenyl)phenylmethanone 

Relevant academic research and scientific papers

Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein

The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.

Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors

A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.

Identification of ligand-binding regions of P-glycoprotein by activated-pharmacophore photoaffinity labeling and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry

Energy dependent efflux pumps confer resistance to anticancer, antimicrobial, and antiparasitic drugs. P-glycoprotein (Pgp, ABCB1) mediates resistance to a broad spectrum of antitumor drugs. Compounds that themselves are nontoxic to cells have been shown to act as inhibitors of Pgp. The mechanism of binding and transport of low-molecular-mass ligands by Pgp is still incompletely understood. This study introduces a series of propafenone-related photoaffinity ligands, which combine high specificity and selectivity for Pgp with high labeling efficiency. Molecules are intrinsically photoactivatable in the arylcarbonyl group, which represents a pharmacophoric substructure for this group of ligand molecules. A detailed study of the structure-activity relationship for this type of photoligand is presented. In subsequent experiments, these ligands were used to characterize the drug-binding domain of propafenone-type analogs. Matrix-assisted laser desorption/ionization - time-of-flight (MALDI-TOF) mass spectrometry shows that propafenone-type ligands preferentially label fragments assigned to putative transmembrane segments 3, 5, 6, 8, 10, 11, and 12. Labeled fragments are also identified in a highly charged region of 15 amino acids in the second cytoplasmic loop. This region corresponds to the so-called EAA-like motif, which has been proposed to play a role in the interaction between transmembrane domain and nucleotide binding domain of peroxisomal ATP-binding cassette transporters. In addition, a region in cytoplasmic loop 3 and between TM12 and the N terminus of the Walker A sequence of NBD2 are labeled by the ligands. Therefore, a number of confined protein regions contribute to the drug-binding domain of propafenone-type analogs.

Synthesis, Pharmacologic Activity, and Structure-Activity Relationships of a Series of Propafenone-Related Modulators of Multidrug Resistance

A series of propanolamines have been prepared and evaluated for multidrug resistance-reverting activity in a human tumor cell model.Structure-activity relationship studies indicate that the phenylpropiophenone moiety as well as the substitution pattern at the nitrogen atom is crucial for activity of the compounds.Incorporation of the ether oxygen into a benzofuran substructure, which renders the compound an arylethanolamine, decreased biologic activity.Highest activity could be observed with the arylpiparazines 4f-h, which not only completely restored daunomycin sensitivity but also showed moderate activity in restoring etoposide toxicity.