474527-76-9Relevant academic research and scientific papers
Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer
Nagasawa, Johnny,Govek, Steven,Kahraman, Mehmet,Lai, Andiliy,Bonnefous, Celine,Douglas, Karensa,Sensintaffar, John,Lu, Nhin,Lee, Kyoungjin,Aparicio, Anna,Kaufman, Josh,Qian, Jing,Shao, Gang,Prudente, Rene,Joseph, James D.,Darimont, Beatrice,Brigham, Daniel,Maheu, Kate,Heyman, Richard,Rix, Peter J.,Hager, Jeffrey H.,Smith, Nicholas D.
, p. 7917 - 7928 (2018/09/06)
About 75% of breast cancers are estrogen receptor alpha (ER-α) positive, and women typically initially respond well to antihormonal therapies such as tamoxifen and aromatase inhibitors, but resistance often emerges. Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and shows some activity in patients who have progressed on antihormonal agents. However, fulvestrant must be administered by intramuscular injections that limit its efficacy. We describe the optimization of ER-α degradation efficacy of a chromene series of ER modulators resulting in highly potent and efficacious SERDs such as 14n. When examined in a xenograft model of tamoxifen-resistant breast cancer, 14n (ER-α degradation efficacy = 91%) demonstrated robust activity, while, despite superior oral exposure, 15g (ER-α degradation efficacy = 82%) was essentially inactive. This result suggests that optimizing ER-α degradation efficacy in the MCF-7 cell line leads to compounds with robust effects in models of tamoxifen-resistant breast cancer derived from an MCF-7 background.
COMBINATIONS OF BENZOPYRAN COMPOUNDS, COMPOSITIONS AND USES THEREOF
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Paragraph 00212, (2015/01/07)
This invention relates to a method of treating a disorder modulated, mediated or affected by the estrogen receptor in a subject comprising administering to the subject a specific benzopyran (in the form of a mixture of S-C2 and R-C2 diastereomers or its pure S-diastereomer) in combination with an agent selected from the group consisting of an mTOR inhibitor, a CDK 4/6 inhibitor, a PI3 Kinase inhibitor, a taxane, an antimetabolite, and an antitumor antibiotic.
SUBSTITUTED BENZOPYRAN COMPOUNDS, COMPOSITIONS AND USES THEREOF
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Paragraph 00105; 00123, (2015/01/07)
Benzopyran compounds with anti-estrogenic activity are provided as Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII and XVIII. These compounds are useful for the treatment or prevention of a variety of conditions that are modulated through the estrogen receptor in mammals including humans.
NOVEL BENZOPYRAN COMPOUNDS, COMPOSITIONS AND USES THEREOF
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Paragraph 00182, (2013/07/05)
Benzopyran compounds with strong anti-estrogenic activity and essentially no estrogenic activity are provided, which are OP- 1038, which is 3-(4-hydroxyphenyl)-4-methyl-2-(4-{2-[(3R)-3-methylpyrrolidin-l-yl]ethoxy}phenyl)-2H-chromen-7-ol, and OP-1074, which is (2S)-3-(4-hydroxyphenyl)-4-methyl-2-(4-{2-[(3R)-3-methylpyrrolidin- 1 -yl]ethoxy}phenyl)-2H-chromen-7-ol. OP-1074 is a pure anti-estrogen when tested in the agonist mode and a complete anti-estrogen when tested in the antagonist mode. These compounds are useful for the treatment or prevention of a variety of conditions that are modulated through the estrogen receptor in mammals including humans.
ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
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, (2012/01/05)
Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
Estrogen receptor ligands. Part 9: Dihydrobenzoxathiin SERAMs with alkyl substituted pyrrolidine side chains and linkers
Blizzard, Timothy A.,Dininno, Frank,Morgan II, Jerry D.,Chen, Helen Y.,Wu, Jane Y.,Kim, Seongkon,Chan, Wanda,Birzin, Elizabeth T.,Yang, Yi Tien,Pai, Lee-Yuh,Fitzgerald, Paula M.D.,Sharma, Nandini,Li, Ying,Zhang, Zhoupeng,Hayes, Edward C.,Dasilva, Carolyn A.,Tang, Wei,Rohrer, Susan P.,Schaeffer, James M.,Hammond, Milton L.
, p. 107 - 113 (2007/10/03)
A series of benzoxathiin SERAMs was prepared. Minor modifications in the side chain or linker resulted in significant effects on biological activity, especially in uterine tissue. A series of dihydrobenzoxathiin SERAMs with alkylated pyrrolidine side chains or alkylated linkers was prepared. Minor modifications in the side chain or linker resulted in significant effects on biological activity, especially in uterine tissue.
Estrogen receptor modulators
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Page 56, (2010/11/29)
The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, and cancer, in particular of the breast, uterus and prostate.
Estrogen receptor modulators
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, (2008/06/13)
The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or preven
