115499-97-3

Upstream product

• 61002-54-8 4-hydroxy-4'-methoxybenzophenone 
• 107-30-2 chloromethyl methyl ether 

Downstream Products

• 671791-56-3 1-(4-methoxymethoxyphenyl)-1-(4-methoxyphenyl)-2-phenylbutan-1-ol 
• 115499-98-4 4-cyano-5-(4-hydroxyphenyl)-(Z)-5-(4-methoxyphenyl)-4-pentenoic acid 
• 110025-28-0 (E/Z)-4-[1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenyl-1-buten-1-yl]-phenol 
• 68392-35-8 4-hydroxytamoxifen 
• 671791-76-7 E/Z-N-[2-hydroxy-5-({2-[(2-{4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenoxy}ethyl)methylamino]ethoxyimino}methyl)benzamide]doxorubicin 
• 850256-34-7 E/Z-1-{4-[2-({2-[2-(2-aminooxyethoxy)ethoxy]ethyl}methylamino)ethoxy]phenyl}-1-(4-hydroxyphenyl)-2-phenylbutene 
• 850256-33-6 E/Z-1-[4-(2-{[2-(2-aminooxyethoxy)ethyl]methylamino}ethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenylbutene 
• 850256-24-5 E/Z-1-(4-{2-[(2-aminooxyethyl)methylamino]ethoxy}phenyl)-1-(4-hydroxyphenyl)-2-phenylbutene 
• 850256-21-2 E/Z-1-[4-(2-bromoethoxy)phenyl]-1-(4-methoxyphenyl)-2-phenylbut-1-ene 
• 850256-19-8 E/Z-1-(4-hydroxyphenyl)-1-(4-methoxyphenyl)-2-phenylbutene 
• 147323-02-2 E/Z-1-[4-(2-bromoethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenylbutene 

Relevant academic research and scientific papers

TARGETED DRUG-FORMALDEHYDE CONJUGATES AND METHODS OF MAKING AND USING THE SAME

The invention provides a prodrug platform technology for improving the therapeutic value of a variety of parent drug compounds by altering and improving drug characteristics such as aqueous solubility, hydrolytic stability, therapeutic index, toxicity profile, pharmacokinetics and selectivity while allowing the potential for synthetic elaboration. The prodrug platform is particularly well suited for targeting therapeutic drugs, including anti-tumor drugs and antibiotics, to specific receptors on target cells (e.g., cancer cells and bacteria). The platform is a technology for providing an improved, preactivated form of a therapeutic drug, and for optionally targeting such drug to target cells or biological molecules. The invention is broadly applicable to many different therapeutic drugs, as well as to a variety of diseases and conditions, including a variety of forms of cancer and bacterial infections.

Design, Synthesis, and Biological Evaluation of Doxorubicin-Formaldehyde Conjugates Targeted to Breast Cancer Cells

The anthracycline antitumor drug doxorubicin (DOX) has been utilized for decades as a broad-spectrum chemotherapeutic. Recent literature evidence documents the role of formaldehyde in the cytotoxic mechanism, and anthracycline-formaldehyde conjugates possess substantially enhanced activity in vitro and in vivo. Targeting a doxorubicin-formaldehyde conjugate specifically to cancer cells may provide a more efficacious chemotherapeutic. The design and 11-step synthesis of doxorubicin-formaldehyde conjugates targeted to the estrogen receptor, which is commonly overexpressed in breast cancer cells, are reported. The formaldehyde is incorporated in a masked form as an N-Mannich linkage between doxorubicin and salicylamide. The salicylamide triggering molecule, previously developed to release the doxorubicin-formaldehyde active metabolite, is tethered via derivatized ethylene glycols to an E and Z mixture of 4-hydroxytamoxifen. The targeting group, E/Z-4-hydroxytamoxifen, was selected for its ability to tightly bind the estrogen receptor and antiestrogen binding sites. The targeted doxorubicin-formaldehyde conjugates' estrogen receptor binding and in vitro growth inhibition were evaluated as a function of tether length. The lead compound, DOX-TEG-TAM, bearing a triethylene glycol tether, binds the estrogen receptor with a binding affinity of 2.5% relative to E/Z-4-hydroxytamoxifen and inhibits the growth of four breast cancer cell lines with 4-fold up to 140-fold enhanced activity relative to doxorubicin.