Synthesis and evaluation of aryl-substituted diarylpropionitriles, selective ligands for estrogen receptor β, as positron-emission tomographic imaging agents

Moon, Byung Seok; Carlson, Kathryn E.; Katzenellenbogen, John A.; Choi, Tae Hyun; Yoon, Dae; Kim, Jung Young; Cheon, Gi Jeong; Koh, Hun Yeong; Lee, Kyo Chul; An, Gwangil

doi:10.1016/j.bmc.2009.02.064

Cited by 11 publications

(4 citation statements)

References 35 publications

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“…The 5-bromo-derivative (162) was the one showing the highest ERb-binding affinity (RBA 5 129%), and its chloroanalogue 163 was only a slightly poorer b ligand. Introduction of a 5-methyl afforded the most b-selective ligand (164) in terms of binding affinity (ERb-RBA 5 24%, b/a 5 40). The ethyl-analogue 165 had lower ERb-binding affinity and selectivity.…”

Section: Isocoumarinsmentioning

confidence: 99%

“…72). 164 All these DPN derivatives are characterized by the presence of a fluorinated substituent in the 3 0 -position, which proved to be well tolerated by ERb. None of the members of this series showed significant binding to ERa (RBA$0.02%), whereas the length of the fluorinated group had a remarkable effect on ERb affinity, the longest group (3-fluoropropyl) being the poorest, with an ERb-RBA of 0.896% (235).…”

Section: Fluorinated and Brominated Analogsmentioning

confidence: 99%

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Estrogen receptor β ligands: Recent advances and biomedical applications

Minutolo

Macchia

Katzenellenbogen

et al. 2011

Medicinal Research Reviews

Self Cite

135

134

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Recent work elucidating the role that the estrogen receptor β (ERβ), a member of the nuclear receptor superfamily, plays in regulating various physiological functions has highlighted the potential of this receptor subtype as a therapeutic target for several pathologies. In fact, molecules that are able to selectively activate ERβ hold promise for the treatment of certain cancers, as well as endometriosis, inflammatory diseases including rheumatoid arthritis, and cardiovascular and CNS conditions. Nevertheless, ERβ remains a challenging target because its ligand-binding cavity is very similar to that present in ERα, and this makes it difficult to develop ligands having sufficient levels of ERβ selectivity for therapeutic use. Nevertheless, considerable advances have recently been made in developing both nonsteroidal and steroidal ERβ-selective agonists. These molecules constitute not only important tools to probe the biological effects of the selective stimulation of ERβ, but some of them appear to be agents with considerable therapeutic potential. This study provides a detailed review of selective ERβ ligands that have been developed recently. After a brief introduction to the structure and nature of the two ERs and the biology of ERβ and its isoforms, the ligands are classified on the basis of their structures and activities. Common pharmacophore elements are highlighted throughout the description of the various chemical classes analyzed, and these elements are presented in a concluding summary overview along with a discussion of potential therapeutic applications of these agents in biomedicine.

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Section: Isocoumarinsmentioning

confidence: 99%

Section: Fluorinated and Brominated Analogsmentioning

confidence: 99%

Estrogen receptor β ligands: Recent advances and biomedical applications

Minutolo

Macchia

Katzenellenbogen

et al. 2011

Medicinal Research Reviews

Self Cite

135

134

View full text Add to dashboard Cite

show abstract

“…PET imaging showed that 18 F-FEDPN had uptake in the animal uterus and ovary, but its specificity was not strong enough for ERβ imaging. Moon et al [ 174 ] eventually synthesized DPN analogs that contain substituents such as methyl, hydroxymethyl, and fluoroethyl, which had a higher selectivity of ERα/ERβ than DPN. However, the absolute ER-β binding affinity was not sufficient and not available for PET imaging.…”

Section: Imaging Receptors In Breast Cancermentioning

confidence: 99%

Radionuclide-Based Imaging of Breast Cancer: State of the Art

Liu

Yuan

et al. 2021

Cancers

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Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.

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“…To remedy this, a deliberate one-pot MOM deprotection step was included in our standard reaction protocol. Thus, lithiation and electrophilic trapping were carried out as per our standard conditions, followed by evaporation and deprotection using HCl (aq) in MeOH at 70 °C for 2 h. 22 After workup and purification, we were furnished with phenolic tetrazole 28 in 70% yield (Scheme 5). Finally, we investigated the possibility of developing an enantioselective lithiation-substitution protocol.…”

mentioning

confidence: 99%

Lithiation Substitution of Unprotected Benzyltetrazoles

et al. 2019

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1H-Tetrazoles occupy an important role in modern medicinal chemistry, but few methods for their modification exist. Many extant protocols require the use of a difficult to remove N-alkyl-protecting group, precluding the products from use as carboxylate bioisosteres, the major role of tetrazoles in pharmaceuticals. We herein report a convenient, protecting-group-free lithiation-substitution protocol for benzylic tetrazoles. Metalation with n-BuLi at 0 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.

show abstract

Synthesis and evaluation of aryl-substituted diarylpropionitriles, selective ligands for estrogen receptor β, as positron-emission tomographic imaging agents

Cited by 11 publications

References 35 publications

Estrogen receptor β ligands: Recent advances and biomedical applications

Estrogen receptor β ligands: Recent advances and biomedical applications

Radionuclide-Based Imaging of Breast Cancer: State of the Art

Lithiation Substitution of Unprotected Benzyltetrazoles

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