ACOLBIFENE

Base Information

• Chemical Name: ACOLBIFENE
• CAS No.: 151533-34-5
• Molecular Formula: C29H31 N O4
• Molecular Weight: 457.569
• Mol file: 151533-34-5.mol

Synonyms:EM 343

Chemical Property of ACOLBIFENE

Chemical Property:

• Boiling Point: 651.5±55.0 °C(Predicted)
• PKA: 9.70±0.40(Predicted)
• PSA: 62.16000
• Density: 1.217±0.06 g/cm3(Predicted)
• LogP: 5.96480

Purity/Quality:

97% ^*data from raw suppliers

rac-Acolbifene ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: The prodrug EM-800 is an orally active nonsteroidal anties trogen and is a triphenylethylene rigid analogue. EM-800 undergoes ester hydrolysis to the active m etabolite acolbifene. This fourth-generation antiestrogen is 200-fold more potent than tam oxifen in breast and uterine cancer cells and is effective in patients for whom tamoxifen therapy has failed. The mechanistic rationale for the effectiveness of acolbifene in tamoxifen-resistant tumors is based on the fact that it inhibits both the AF-1 and AF-2 activation pathways and does not poss ess any intrinsic estrogenic action. Acolbifene enjoys a 60% breast cancer cure rate. Structurally, acolbifene resembles raloxifene, with a benzopyran ring substituted for the benz othiophene ring. An additional benefit observed with acolbifene is its protective effect on bone loss. Adverse effects include nausea and vomiting.
• Uses: rac-Acolbifene is a reacemic compound of Acolbifene (A190230) which is a selective estrogen receptor modulator (SERM) acting as pure antiestrogen. Acolbifene is also the orally active antiestrogen which is the most potent of the known antiestrogens and exerts pure antiestrogenic activity in the mammary gland and endometrium.

Technology Process of ACOLBIFENE

There total 7 articles about ACOLBIFENE which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 62.5%

C33H37NO6 + methylmagnesium bromide (75-16-1) + 2-(4''-[2'''-piperidinoethoxy]phenyl)-3-(4'-tetrahydropyranyloxyphenyl)-7-tetrahydropyranyloxy-2,3-dihydro-4H-1-benzopyran-4-one (151533-32-3) + 3-(4-hydroxy-phenyl)-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-7-(tetrahydro-pyran-2-yloxy)-chroman-4-one (690274-19-2) → 2-[4-[2-(1-piperidino)ethoxy]phenyl]-3-(4-hydroxyphenyl)-4-methyl-7-hydroxy-2H-1-benzopyran (151533-34-5)

Guidance literature:

C₃₃H₃₇NO₆; methylmagnesium bromide; 2-(4''-[2'''-piperidinoethoxy]phenyl)-3-(4'-tetrahydropyranyloxyphenyl)-7-tetrahydropyranyloxy-2,3-dihydro-4H-1-benzopyran-4-one; 3-(4-hydroxy-phenyl)-2-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-7-(tetrahydro-pyran-2-yloxy)-chroman-4-one; In tetrahydrofuran; diethyl ether; at -40 - 20 ℃;

With acetic acid; In water; at 23 - 80 ℃; for 0.75h;

Reference yield:

4-hydroxy-4-methyl-2-(4'-[2''-piperidino]ethoxy)phenyl-3-(4'''-tetrahydropyranyloxy)phenyl-7-tetrahydropyranyloxychromane (151533-33-4) → 2-[4-[2-(1-piperidino)ethoxy]phenyl]-3-(4-hydroxyphenyl)-4-methyl-7-hydroxy-2H-1-benzopyran (151533-34-5)

Guidance literature:

With acetic acid; at 90 ℃; for 0.5h; Yield given;

DOI:10.1021/jm970095o

Reference yield:

2,4,4'-trihydroxy deoxybenzoin (17720-60-4,423150-69-0) → 2-[4-[2-(1-piperidino)ethoxy]phenyl]-3-(4-hydroxyphenyl)-4-methyl-7-hydroxy-2H-1-benzopyran (151533-34-5)

Guidance literature:

Multi-step reaction with 4 steps

1: 69 percent / TsOH / 2.5 h / 0 °C

2: 1.) piperidine, 2.) Cs₂CO₃, H₂O / 1.) benzene, reflux, 60 h, 2.) acetone, reflux, 19 h

3: tetrahydrofuran / 3 h / -78 - 20 °C

4: aq. AcOH / 0.5 h / 90 °C

With piperidine; water; caesium carbonate; toluene-4-sulfonic acid; acetic acid; In tetrahydrofuran;

DOI:10.1021/jm970095o

upstream raw materials:

4-hydroxy-4-methyl-2-(4'-[2''-piperidino]ethoxy)phenyl-3-(4'''-tetrahydropyranyloxy)phenyl-7-tetrahydropyranyloxychromane

2,4,4'-trihydroxy deoxybenzoin

4-hydroxyphenylacetate

1-(2-hydroxy-4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)ethanone

Downstream raw materials:

EM-762

EM-800

EM-776

Acolbifene