Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Tetrasubstituted alkene compounds and their use

A compound, enamide technology, applied in the field of tetra-substituted olefin compounds and their uses, which can solve problems such as loss of bone density, increased risk of endometrial cancer, etc.

Active Publication Date: 2018-03-27
EISIA R&D MANAGEMENT CO LTD
View PDF4 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are definite predispositions associated with these different classes of compounds
For example, tamoxifen has been shown to activate signaling activity in the endometrium leading to a clinically increased risk of endometrial cancer (Fisher et al. (1994) J Natl Cancer Inst. Apr 6; 86(7) :527-37; van Leeuwen et al. (1994) Lancet Feb 19; 343(8895):448-52)
Conversely, since fulvestrant is a pure antagonist, it may cause loss of bone density in postmenopausal women, since ERα activity is critical for bone building

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Tetrasubstituted alkene compounds and their use
  • Tetrasubstituted alkene compounds and their use
  • Tetrasubstituted alkene compounds and their use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 101

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156]

[0157]

[0158]

[0159]

[0160] General procedure

[0161] The following abbreviations can be used here:

[0162] ACN: Acetonitrile

[0163] BOC: tert-butoxycarbonyl

[0164] CAN: Ammonium cerium nitrate

[0165] Conc.: concentrated

[0166] Cs 2 CO 3 : cesium carbonate

[0167] DABCO: 1,4-diazabicyclo[2.2.2]octane

[0168] DCM: dichloromethane

[0169] DHP: dihydropyran

[0170] DIPEA: N,N-diisopropylethylamine, Hunig's base

[0171] DMA: Dimethylacetamide

[0172] DMF: Dimethylformamide

[0173] DMSO: Dimethylsulfoxide

[0174] DPEphos: (oxydi-2,1-phenylene)bis(diphenylphosphine)

[0175] EDCI.HCl: N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride

[0176] EtOH: ethanol

[0177] EtOAc: ethyl acetate

[0178] Et 3 N: Triethylamine

[0179] Ex.: Example

[0180] h: hours

[0181] HATU: 1-[bis(dimethylamino)methylene]...

Embodiment 1

[0248] Example 1: (E)-4-((2-(4-((E)-1-(1H-indazol-5-yl)-2-phenylbut-1-en-1-yl)benzene Synthesis of Oxy)ethyl)amino)-N,N-Dimethylbut-2-enamide (Compound 1)

[0249] Step 1: Synthesis of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

[0250]

[0251] According to Scheme 1 step 1, the reaction was carried out with 5-bromo-1H-indazole (5 g, 23.5 mmol) instead of compound 201. Purification of the crude material by column chromatography on 230-400 mesh silica using 4-5% ethyl acetate in hexane afforded the title compound of Example 1, step 1 as a pale yellow oil (12.6 g, 86 %).

[0252] Step 2: Synthesis of but-1-yn-1-yltrimethylsilane:

[0253]

[0254] To a stirred solution of (trimethylsilyl)acetylene (116 g, 1.19 mol) in anhydrous THF (400 mL) was added n-BuLi (2.5 M in THF) at -78 °C over 2 hours. , 500mL). The resulting mixture was warmed to 0 °C for 10 min. The reaction mixture was cooled to -78°C again, HMPA (234 g, 1.13 mol) was added to the above mixture, an...

Embodiment 1A

[0282] Example 1A - Synthesis of the Hydrochloride Salt of Compound 1

[0283] Step 1A: Synthesis of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

[0284]

[0285] 5-Bromoindazole (11.0Kg, 0.055mol), acetonitrile (110L) and PTSA (1.0Kg, 0.055mol) were added to a clean, dry nitrogen-flushed 200L glass reactor, and the reaction mixture was heated at 28- Stir at 30°C for 30 minutes. To the above solution was added dihydropyran (7.03 Kg, 2.55 mol) dropwise over 20 minutes. The resulting mixture was stirred at room temperature for 16 hours. After completion as monitored by TLC, the reaction mixture was quenched with water (500 mL), and the acetonitrile was concentrated under reduced pressure. The obtained product was extracted with ethyl acetate (25 l x 3), the combined organic extracts were washed with water, then brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the desired compound, which was not After further purification, it...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and / or the subject in need of treatment may express a mutantER-alpha protein.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application No. 62 / 168,581, filed May 29, 2015, U.S. Provisional Patent Application No. 62 / 168,529, filed May 29, 2015, and U.S. Priority of Provisional Application No. 62 / 269,745. Background technique [0003] Breast cancer is the most commonly diagnosed malignancy in women today, with nearly 200,000 / 1.7 million new cases diagnosed each year in the United States / worldwide, respectively. Since approximately 70% of breast tumors are positive for estrogen receptor alpha (ERα), a key oncogenic driver in this subtype of tumors, several types of therapeutic agents have been developed to antagonize ERα functions, including 1) selective estrogen receptor down-regulators (SERDs), such as fulvestrant, 2) selective estrogen receptor modulators (SERMs), such as tamoxifen, and 3) aromatase inhibitors that lower systemic estrogen levels. These therapeutic agents have been clinically effecti...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/4439C07D317/02C07D317/06C07D487/04
CPCC07D231/56C07D401/06C07D401/14C07D471/04A61P35/00A61P15/00C07D471/14C07D403/06C07D403/12A61K31/416C07D317/02C07D317/06
Inventor 马克·巴克郝鸣鸿玛那芙·寇波维贾·库莫·涅维奈蒂濮阳晓玲苏珊塔·撒马杰达彼得·盖瑞德·史密斯王渊郑国茱朱平
Owner EISIA R&D MANAGEMENT CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com