879892-86-1

Upstream product

• 693818-54-1 4-(4-methoxyphenyl)-3-phenyl-4-(3-pivaloyloxyphenyl)but-1-ene 
• 103-82-2 phenylacetic acid 
• 100-66-3 methoxybenzene 
• 40595-34-4 (E)-trimethyl(3-phenylallyl)silane 
• 134518-89-1 3-pivaloyloxybenzaldehyde 

Downstream Products

• 82413-20-5 Droloxifene 
• 879892-92-9 3,5-dinitro-benzoic acid 3-{1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-phenyl-but-1-enyl}-phenyl ester 
• 879892-90-7 3,5-Dinitro-benzoic acid 3-[(E)-1-(4-hydroxy-phenyl)-2-phenyl-but-1-enyl]-phenyl ester 
• 879892-96-3 2,2-dimethyl-propionic acid 3-{1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-phenyl-but-1-enyl}-phenyl ester 
• 879893-00-2 2,2-Dimethyl-propionic acid 3-{(E)-1-[4-(2-dimethylamino-ethoxy)-phenyl]-2-phenyl-but-1-enyl}-phenyl ester 
• 879892-94-1 3-{1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-phenyl-but-1-enyl}-phenol 
• 879892-98-5 2,2-Dimethyl-propionic acid 3-[(E)-1-(4-hydroxy-phenyl)-2-phenyl-but-1-enyl]-phenyl ester 
• 879892-88-3 3,5-Dinitro-benzoic acid 3-[(E)-1-(4-methoxy-phenyl)-2-phenyl-but-1-enyl]-phenyl ester 

Relevant academic research and scientific papers

Searching for an ideal SERM: Mining tamoxifen structure–activity relationships

The repurposing of old drugs for new treatments has recently garnered increased attention in the face of new diseases and declining productivity of the pharmaceutial industry. This report draws attention to potential opportunities hiding in plain sight within the SAR of off-patent drugs. Herein we explore the untapped potential of Selective Estrogen Receptor Modulators (SERMs). SERMs are a class of molecules that have been highly influential in the treatment of estrogen receptor-positive breast cancers. However, the most commonly prescribed SERM, tamoxifen, has been found to increase the risk of endometrial cancer. Another SERM, raloxifene, does not increase incidence of endometrial cancer, but has been abandoned as a breast cancer treatment. We report the design, synthesis, and evaluation of an unexplored tamoxifen substitution pattern which mimics the geometry of raloxifene to confer its favorable pharmacodynamics. This substitution pattern was found to maintain excellent binding affinity to estrogen receptor-α.

An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole

Two new synthetic pathways to the anti-cancer agent tamoxifen and its derivatives were developed. The first route involved the aldol reaction of benzyl phenyl ketone with acetaldehyde followed by Friedel-Crafts substitution with anisole in the presence of Cl2Si(OTf)2 to produce 1,1,2-triaryl-3-acetoxybutane, a precursor of the tamoxifen derivatives. The second one utilized the novel three-component coupling reaction among aromatic aldehydes, cinnamyltrimethylsilane, and aromatic nucleophiles using HfCl4 as a Lewis acid catalyst to produce 3,4,4-triarylbutene, that is also a valuable intermediate of the tamoxifen derivatives. The former strategy requires a total of 10 steps from the aldol formation to the final conversion to tamoxifen, whereas the latter needs only three or four steps to produce tamoxifen and droloxifene including the installation of the side-chain moiety and the base-induced double-bond migration to form the tetra-substituted olefin structure. This synthetic strategy seems to serve as a new and practical pathway to prepare not only the tamoxifen derivatives but also the other SERMs (selective estrogen receptor modulators) including estrogen-dependent breast cancer and osteoporosis agents.

Short-step synthesis of droloxifene via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole

A short-step route for the preparation of droloxifene has been established via the novel three-component coupling reaction among 3-pivaloyloxybenzaldehyde, cinnamyltrimethylsilane, and β-chlorophenetole, the successive installation of the side-chain part, and the base-induced migration of the double bond. The present synthesis of tetra-substituted ethylene moieties is a widely applicable strategy for producing a variety of SERMs (selective estrogen receptor modulators) and SARMs (selective androgen receptor modulators), such as tamoxifen, raloxifene, and other compounds that can lead to new drugs.