176672-06-3

Usage

Uses

Used in Pharmaceutical Industry:
3-Bromo-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene is used as an intermediate in the synthesis of nonsteroidal, selective estrogen receptor modulator (SERM) for the development of Raloxifene (R100000). 3-broMo-6-Methoxy-2-(4-Methoxyphenyl)benzo[b]thiophene plays a crucial role in the production of Raloxifene, a medication used to treat and prevent osteoporosis in postmenopausal women and reduce the risk of breast cancer.
The compound's specific structural features allow it to be a valuable building block in the creation of SERMs, which are important for their ability to modulate estrogen receptor activity in a tissue-specific manner. This makes them useful in treating conditions related to estrogen deficiency while minimizing the risk of hormone-dependent side effects.

Upstream product

• 63675-74-1 2-(4'-methoxyphenyl)-6-methoxybenzothiophene 
• 90560-10-4 6-methoxy-benzo[b]thiophene 
• 96803-85-9 1-[(2,2-diethoxyethyl)sulfanyl]-3-methoxybenzene 
• 15570-12-4 3-methoxybenzenethiol 
• 1163701-10-7 (5-methoxy-2-((4-methoxyphenyl)ethynyl)phenyl)(methyl)-sulfane 
• 1163700-92-2 2-bromo-4-methoxy-1-((4-methoxyphenyl)ethynyl)benzene 
• 696-62-8 para-iodoanisole 

Downstream Products

• 189286-85-9 2-(4-methoxyphenyl)-3-[N-(4-benzyloxyphenyl)acetamido]-6-methoxy-benzo[b]thiophene 
• 182133-00-2 2-(4'-methoxyphenyl)-3-bromo-6-methoxybenzo[b]thiophene S-oxide 
• 320575-21-1 1,2-bis(4'-methoxyphenyl)-2'-(3'',4'',5''-trimethoxyphenylthioether)ethyne S-oxide 
• 189286-86-0 2-(4-methoxyphenyl)-3-[N-(4-hydroxyphenyl)acetamido]-6-methoxy-benzo[b]thiophene 
• 182133-03-5 6-methoxy-3-{4-[2-(1-piperidinyl)ethoxy]phenoxy}-2-(4-methoxyphenyl)benzo[b]thiophene S-oxide 
• 189286-83-7 1-(2-{4-[6-Methoxy-2-(4-methoxy-phenyl)-1-oxo-1H-1λ⁴-benzo[b]thiophen-3-ylsulfanyl]-phenoxy}-ethyl)-piperidine 
• 189286-88-2 2-(4-methoxyphenyl)-3-[N-[4-[2-(1-piperidinyl)ethoxy]phenyl]acetamido]-6-methoxybenzo[b]thiophene 
• 205814-59-1 2-(4-methoxyphenyl)-3-(3-benzyloxyphenyl)-6-methoxybenzo[b]thiophene 
• 1261352-31-1 C₂₂H₁₈O₃S 

Relevant academic research and scientific papers

Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzo[b]thiophene derivatives as potent apoptosis-inducing agents

Many clinically used agents active in cancer chemotherapy exert their activity through the induction of cell death (apoptosis) by targeting microtubules, altering protein function or inhibiting DNA synthesis. The benzo[b]thiophene scaffold holds a pivotal place as a pharmacophore for the development of anticancer agents, and, in addition, this scaffold has many pharmacological activities. We have developed a flexible method for the construction of a new series of 2-aryl-3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophenes as potent antiproliferative agents, giving access to a wide range of substitution patterns at the 2-position of the 6-methoxybenzo[b]thiophene common intermediate. In the present study, all the synthesized compounds retained the 3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophene moiety, and the structure–activity relationship was examined by modification of the aryl group at its 2-position with electron-withdrawing (F) or electron-releasing (alkyl and alkoxy) groups. We found that small substituents, such as fluorine or methyl, could be placed in the para-position of the 2-phenyl ring, and these modifications only slightly reduced antiproliferative activity relative to the unsubstituted 2-phenyl analogue. Compounds 3a and 3b, bearing the phenyl and para-fluorophenyl at the 2-position of the 6-methoxybenzo[b]thiophene nucleus, respectively, exhibited the greatest antiproliferative activity among the tested compounds. The treatment of both Caco2 (not metastatic) and HCT-116 (metastatic) colon carcinoma cells with 3a or 3b triggered a significant induction of apoptosis as demonstrated by the increased expression of cleaved-poly(ADP-ribose) polymerase (PARP), receptor-interacting protein (RIP) and caspase-3 proteins. The same effect was not observed with non-transformed colon 841 CoN cells. A potential additional effect during mitosis for 3a in metastatic cells and for 3b in non-metastatic cells was also observed.

Discovery of LSZ102, a potent, orally bioavailable selective estrogen receptor degrader (SERD) for the treatment of estrogen receptor positive breast cancer

In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERα positive breast cancer.

COMPOUNDS AND COMPOSITIONS AS SELECTIVE ESTROGEN RECEPTOR DEGRADERS

The present invention relates to compounds of formula I: in which n, m, X, Y1, R1, R2, R3, R4 and R5 are defined in the Summary of the Invention; capable of being both potent antagonists and degraders of estrogen receptors. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with aberrant estrogen receptor activity.

A Chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy

Breast cancer remains a significant cause of death in women, and few therapeutic options exist for estrogen receptor negative (ER (-)) cancers. Epigenetic reactivation of target genes using histone deacetylase (HDAC) inhibitors has been proposed in ER (-) cancers to resensitize to therapy using selective estrogen receptor modulators (SERMs) that are effective in ER (+) cancer treatment. Based upon preliminary studies in ER (+) and ER (-) breast cancer cells treated with combinations of HDAC inhibitors and SERMs, hybrid drugs, termed SERMostats, were designed with computational guidance. Assay for inhibition of four typea I HDAC isoforms and antagonism of estrogenic activity in two cell lines yielded a SERMostat with 1-3a μM potency across all targets. The superior hybrid caused significant cell death in ER (-) human breast cancer cells and elicited cell death at the same concentration as the parent SERM in combination treatment and at an earlier time point.

COMPOSITIONS AND METHODS FOR TREATING ESTROGEN-RELATED MEDICAL DISORDERS

Disclosed herein are methods for treatment of estrogen-related medical disorders. The methods of treatment may comprise administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (I) or a pharmaceutically acceptable salt thereof.

Synthesis of a 3-(α-Styryl)benzo[ b ]-thiophene Library via Bromocyclization of Alkynes and Palladium-Catalyzed Tosylhydrazones Cross-Couplings: Evaluation as Antitubulin Agents

A library of functionalized 3-(α-styryl)-benzo[b]thiophenes, endowed with a high level of molecular diversity, was efficiently synthesized by applying a synthetic sequence that allowed introduction of various substituents on aromatic A, B, and C-rings. Th

N-SUBSTITUTED AZETIDINE DERIVATIVES

The present invention relates to novel N-substituted azetidine derivatives to pharmaceutical compositions comprising these compounds and to their use in therapy, in particular to their use for the prevention or treatment of ovulatory dysfunction, uterine cancer, endometrium cancer, ovarian cancer, endometriosis, osteoporosis, prostate cancer, benign prostatic hypertrophy, and breast cancer, in particular ER-positive breast cancer, more in particular ER- positive, hormone treatment-resistant breast cancer. Said N-substituted azetidine derivatives have estrogen receptor alpha (ERa) antagonistic and - in certain embodiments - selective estrogen receptor downregulating (SERD) activity in ER-positive breast cancer cells.

Acrylic and propionic acid compounds, intermediates, processes, compositions, and method

This invention is directed to a class of acrylic and propionic acid compounds and their use in the treatment of post-menopausal symptoms and restenosis. In other embodiments, the invention is directed to intermediates and to processes for the preparation of the acrylic and propionic acid compounds.

Treatment of central nervous system disorders with selective estrogen receptor modulators

The present invention provides a method of treating depression, mood swings, or Alzheimer's disease in a patient in need of such treatment by administering a selective estrogen receptor modulating compound of the formula in which R1 and R2 are independently hydroxy and alkoxy of one to four carbon atoms; and R3 and R4 are independently methyl or ethyl, or R3 and R4, taken together with the nitrogen atom to which they are attached, form a pyrrolidino, methyl-pyrrolidino, dimethylpyrrolidino, piperidino, morpholino, or hexamethyleneimino ring.