85384-17-4

Upstream product

• 2491-32-9 1-(4-Hydroxyphenyl)-2-phenylethanone 
• 4584-46-7 (2-chloroethyl)dimethylamine hydrochloride 
• 622-86-6 2-chloroethoxybenzene 
• 103-82-2 phenylacetic acid 
• 19561-95-6 1-<4-(2-chloroethoxy)phenyl>-2-phenylethanone 
• 124-40-3 dimethyl amine 

Relevant academic research and scientific papers

Novel compounds that reverse the disease phenotype in Type 2 Gaucher disease patient-derived cells

Gaucher disease (GD) results from inherited mutations in the lysosomal enzyme β-glucocerobrosidase (GCase). Currently available treatment options for Type 1 GD are not efficacious for treating neuronopathic Type 2 and 3 GD due to their inability to cross the blood-brain barrier. In an effort to identify small molecules which could be optimized for CNS penetration we identified tamoxifen from a high throughput phenotypic screen on Type 2 GD patient-derived fibroblasts which reversed the disease phenotype. Structure activity studies around this scaffold led to novel molecules that displayed improved potency, efficacy and reduced estrogenic/antiestrogenic activity compared to the original hits. Here we present the design, synthesis and structure activity relationships that led to the lead molecule Compound 31.

NOVEL FUNCTIONALIZED N,N-DIALKYLAMINO PHENYL ETHERS AND THEIR METHOD OF USE

Pharmaceutical compositions of the invention comprise functionalized N,N-dialkylamino phenyl ethers derivatives having a disease-modifying action in the treatment of diseases associated with lysosomal storage dysfunction that include Gaucher's disease, and any disease or condition involving lysosomal storage dysfunction.

Flexible estrogen receptor modulators: Design, synthesis, and antagonistic effects in human MCF-7 breast cancer cells

Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds' potential interactions with specific residues within the human estrogen receptor α ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.

Erythro-1,2-1-pentanones

Erythro-1,2,3-triphenyl-1-pentanones of Formula 1 STR1 wherein R1 may be a dimethylamino, diethylamino, piperidin-1-yl- or pyrrolidin-1-yl group and R2 represents a hydrogen atom, a methoxy or hydroxy group, and their pharmacologically acceptable salts, have a pronounced antiestrogenic effect and are suitable for the treatment of hormone-dependent tumors. They may be prepared by reacting 1,2-diphenyl-ethanone of Formula 2 STR2 wherein R1 is as set forth in Formula 1 and R2 represents a hydrogen atom or a methoxy group, with sodium hydride in anhydrous dimethyl-formamide, isolating after conversion with 1-chloro-1-phenylpropane, the erythro form from the reaction product and possibly releasing the hydroxy group from the methoxy group by selective cleavage with hydrobromic acid.