Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders
| Title: | Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders |
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| Patent Number: | 9,561,211 |
| Publication Date: | February 07, 2017 |
| Appl. No: | 15/066425 |
| Application Filed: | March 10, 2016 |
| Abstract: | The present invention relates to compounds of formula I: [chemical expression included] 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. |
| Inventors: | Burks, Heather Elizabeth (Cambridge, MA, US); Dechantsreiter, Michael A. (Cambridge, MA, US); He, Guo (Cambridge, MA, US); Nunez, Jill (Cambridge, MA, US); Peukert, Stefan (Cambridge, MA, US); Springer, Clayton (Cambridge, MA, US); Sun, Yingchuan (Cambridge, MA, US); Thomsen, Noel Marie-France (Cambridge, MA, US); Tria, George Scott (Cambridge, MA, US); Yu, Bing (Cambridge, MA, US) |
| Assignees: | Novartis AG (Basel, CH) |
| Claim: | 1. A method of treating a cancer selected from breast, ovarian, endometrial, prostate, uterine, cervical and lung, comprising administering to a subject in need of such treatment an effective amount of a compound, or a pharmaceutically acceptable salt thereof, having the structure: [chemical expression included] |
| Claim: | 2. The method of claim 1 , further comprising administering to the subject an additional therapeutic agent. |
| Claim: | 3. The method of claim 2 , wherein the additional therapeutic agent comprises an anticancer drug, a pain medication, an antiemetic, an antidepressant or an anti-inflammatory agent. |
| Patent References Cited: | 5510357 April 1996 Palkowitz 5731342 March 1998 Cullinan et al. 6166069 December 2000 Malamas et al. 8877801 November 2014 Burks et al. 2004/0044059 March 2004 Pinney et al. 2004/0132776 July 2004 Agus 2009/0069380 March 2009 Czarnik 0716855 June 1996 0731101 September 1996 95/10513 April 1995 98/39323 September 1998 98/45286 October 1998 98/45287 October 1998 98/45288 October 1998 99/58519 November 1999 01/66098 September 2001 2004/009086 January 2004 2005/000834 January 2005 2005/073190 August 2005 2005/073205 August 2005 2006/094235 September 2006 2008/115686 September 2008 2012/084711 June 2012 |
| Other References: | Kieser et al. Characterization of the pharmacophore properties of novel selective estrogen receptor downregulators (SERDs). J Med Chem. Apr. 22, 2010;53(8):3320-9. cited by applicant Overk et al., Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene. ChemMedChem. Oct. 2007;2(10):1520-6. cited by applicant Scott et al., “Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat,” ACS Med Chem Lett. Accepted Dec. 19, 2015 (pp. A-F) (6 pages). cited by applicant Xiong et al., “Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer,” J Med Chem. (pp. A-S) (19 pages). cited by applicant Kieser, KJ. et al.Characterization of the Pharmacophore Properties of Novel Selective Estrogen ReceptorDownRegulators (SERDs). J. Med. Chem., 53(8): 3320-3329. (2010). cited by applicant |
| Primary Examiner: | Ricci, Craig |
| Attorney, Agent or Firm: | Reid, Scott W. |
| Accession Number: | edspgr.09561211 |
| Database: | USPTO Patent Grants |
| Language: | English |
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