91444-54-1

Usage

Uses

Used in Pharmaceutical Industry:
2-(4-Hydroxyphenyl)-3-methyl-1H-indol-5-ol is used as a reagent in the synthesis of tethered indoles. These indoles serve as functionalizable ligands for estrogen receptors. 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol plays a crucial role in the development of pharmaceuticals targeting estrogen-related conditions, such as hormone-dependent cancers and other diseases influenced by estrogen levels.
In the synthesis process, 2-(4-Hydroxyphenyl)-3-methyl-1H-indol-5-ol can be further modified or combined with other molecules to create a diverse range of tethered indole derivatives. These derivatives can then be evaluated for their binding affinity, selectivity, and biological activity towards estrogen receptors, leading to the potential discovery of new therapeutic agents.
The use of 2-(4-Hydroxyphenyl)-3-methyl-1H-indol-5-ol in the pharmaceutical industry highlights its importance in the design and synthesis of novel ligands that can modulate estrogen receptor activity. This can contribute to the advancement of treatments for various health conditions, making it a valuable compound in the field of medicinal chemistry.

Upstream product

• 91444-18-7 5-methoxy-2-(4-methoxyphenyl)-3-methyl-1H-indole 
• 54049-23-9 4-hydroxyphenylhydrazine hydrochloride 
• 70-70-2 4-hydroxypropiophenone 
• 1610763-22-8 1-(4-(benzyloxy)phenyl)-2-((4-(methoxymethoxy)phenyl)amino)propan-1-one 
• 876-30-2 4-methoxymethyloxyaniline 
• 123-30-8 4-amino-phenol 
• 7107-59-7 4-(N-Benzyloxycarbonylamino)phenol 
• 1610763-24-0 2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-5-ol 
• 198479-63-9 5-benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1H-indole 
• 4495-66-3 4-benzyloxypropiophenone 
• 35081-45-9 1-<4-(benzyloxy)phenyl>-2-bromo-1-propanone 
• 104-94-9 4-methoxy-aniline 
• 21086-33-9 2-bromo-1-(4-methoxyphenyl)-1-propanone 

Downstream Products

• 198481-32-2 bazedoxifene 
• 91444-18-7 5-methoxy-2-(4-methoxyphenyl)-3-methyl-1H-indole 
• 91444-55-2 4-(5-acetoxy-3-methyl-1H-indol-2-yl)phenyl acetate 
• 1124291-70-8 C₂₁H₂₅NO₂ 

Relevant academic research and scientific papers

METHODS OF PREPARINGBAZEDOXIFENE BY NEW INTERMEDIATES

The present invention relates to a method for manufacturing novel bazedoxifene or a pharmaceutically acceptable salt thereof. A manufacturing method according to the present invention can provide high purity and high yield of bazedoxifene, and is economical in terms of time and cost and eco-friendly due to a relatively simple manufacturing process, thereby being able to be usefully applied to mass production.COPYRIGHT KIPO 2020

METHODS OF PREPARING　BAZOEDOXIFENE

The present invention relates to novel bazedoxifene or to a method for producing a pharmaceutically acceptable salt thereof. The production method according to the present invention can provide the bazedoxifene with high purity and high yield, and is economical and environmentally friendly in terms of time and cost due to a relatively simple manufacturing process to be usefully applied to mass production.COPYRIGHT KIPO 2018

Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles

Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We describe the design and synthesis of novel SERM type ligands based on the 2-arylindole scaffold to selectively target the estrogen receptor in hormone dependent breast cancers. Some of these novel compounds are designed as bisindole type structures, while others are conjugated to a cytotoxic agent based on combretastatin A4 (CA4) which is a potent inhibitor of tubulin polymerisation. The indole compounds synthesised within this project such as 31 and 86 demonstrate estrogen receptor (ER) binding and strong antiproliferative activity in the ER positive MCF-7 breast cancer cell line with IC50values of 2.71?μM and 1.86?μM respectively. These active compounds induce apoptotic activity in MCF-7 cells with minimal effects on normal peripheral blood cells. Their strong anti-cancer effect is likely mediated by the presence of two ER binding ligands for 31 and an ER binding ligand combined with a cytotoxic agent for 86.

Bazedoxifene-scaffold-based mimetics of solomonsterols A and B as novel pregnane x receptor antagonists

Pregnane X receptor (PXR), a member of the NR1I nuclear receptor family, acts as a xenobiotic sensor and a paramount transcriptional regulator of drug-metabolizing enzymes and transporters. The overexpression of PXR in various cancer cells indicates the importance of PXR as a drug target for countering multidrug resistance in anticancer treatments. We describe the discovery of novel bazedoxifene-scaffold-based PXR antagonists inspired by the marine sulfated steroids solomonsterol A and B as natural leads. A luciferase reporter assay on a PXR-transfected HepG2 cell line identified compounds 19-24 as promising PXR antagonists. Further structure-activity relationship studies of the most active PXR antagonist from the series (compound 20, IC50 = 11 μM) revealed the importance of hydroxyl groups as hydrogen-bond donors for PXR antagonistic activity. PXR antagonists 20 and 24 (IC50 = 14 μM), in addition to the downregulation of PXR expression, exhibited inhibition of PXR-induced CYP3A4 expression, which illustrates their potential to suppress PXR-regulated phase-I drug metabolism.

In vitro bioactivation of bazedoxifene and 2-(4-hydroxyphenyl)-3-methyl-1H- indol-5-ol in human liver microsomes

Bazedoxifene is a selective estrogen receptor modulator (SERM) that has been developed for use in post-menopausal osteoporosis. However, it contains a potentially toxic 5-hydroxy-3-methylindole moiety. Previous studies on the 5-hydroxyindole and the 3-alkylindole-containing drugs indometacine, zafirlukast and MK-0524 structural analogs have shown that they are bioactivated by cytochrome P450s through a dehydrogenation process to form quinoneimine or 3-methyleneindolenine electrophilic species. In the present study, bazedoxifene was synthesized and then evaluated, together with raloxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol (13), a 3-methyl-5-hydroxyindole- based structural fragment of bazedoxifene, for its ability to form reactive electrophilic species when incubated with human liver microsomes (HLMs) or recombinant CYP isozymes. We showed that bazedoxifene was bioactivated only in trace amounts with recombinant CYP isozymes. In contrast, the N-dealkylated fragment of bazedoxifene (2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol) was bioactivated in considerable amounts to an electrophilic intermediate, which was trapped with glutathione and identified by LC-MS/MS. This suggests that bazedoxifene would require initial N-dealkylation, which could subsequently lead to the formation of the reactive intermediate. However, such an N-dealkylated metabolite of bazedoxifene was not detected after the incubation of bazedoxifene in HLM or recombinant CYP isozymes.

Tethered indoles as functionalizable ligands for the estrogen receptor

To create ligands for the estrogen receptor that contain pendant groups for tethering to a poly(amido)amine (PAMAM) dendrimer, we have explored a class of N-substituted 2-phenyl indoles. Attachment of tethers of different length and chemical nature to thi

2-Phenylindoles. Relationship between Structure, Estrogen Receptor Affinity, and Mammary Tumor Inhibiting Activity in the Rat

A number of 2-phenylindole derivatives with one hydroxy group in the meta or para position of the phenyl ring and a second one in position 5, 6, or 7 of the indole nucleus were synthesized.In addition, different alkyl groups were introduced into positions