PE20210400A1 - Degradadores selectivos del receptor de estrogeno - Google Patents
Degradadores selectivos del receptor de estrogenoInfo
- Publication number
- PE20210400A1 PE20210400A1 PE2020002017A PE2020002017A PE20210400A1 PE 20210400 A1 PE20210400 A1 PE 20210400A1 PE 2020002017 A PE2020002017 A PE 2020002017A PE 2020002017 A PE2020002017 A PE 2020002017A PE 20210400 A1 PE20210400 A1 PE 20210400A1
- Authority
- PE
- Peru
- Prior art keywords
- cancer
- benzopyrano
- azetidin
- quinolin
- fluoromethyl
- Prior art date
Links
- 239000001064 degrader Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 208000002495 Uterine Neoplasms Diseases 0.000 abstract 2
- 206010046766 uterine cancer Diseases 0.000 abstract 2
- BGOOMSGEXIBXHQ-UHFFFAOYSA-N 5-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-7-(trifluoromethyl)-5H-chromeno[4,3-c]quinolin-2-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)C1OC2=C(C=CC=C2C(F)(F)F)C=2C=NC=3C=C(C=CC=3C=21)O BGOOMSGEXIBXHQ-UHFFFAOYSA-N 0.000 abstract 1
- UVBQMXOKKDCBJN-UHFFFAOYSA-N 5-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8-(trifluoromethyl)-5H-chromeno[4,3-c]quinolin-2-ol Chemical compound FCC1CN(C1)CCOC1=CC=C(C=C1)C1OC2=C(C=CC(=C2)C(F)(F)F)C=2C=NC=3C=C(C=CC=3C=21)O UVBQMXOKKDCBJN-UHFFFAOYSA-N 0.000 abstract 1
- HPRZXPUOMAQVBB-UHFFFAOYSA-N 8-chloro-5-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-5H-chromeno[4,3-c]quinolin-2-ol Chemical compound ClC1=CC2=C(C=C1)C=1C=NC=3C=C(C=CC=3C=1C(O2)C1=CC=C(C=C1)OCCN1CC(C1)CF)O HPRZXPUOMAQVBB-UHFFFAOYSA-N 0.000 abstract 1
- 206010006187 Breast cancer Diseases 0.000 abstract 1
- 208000026310 Breast neoplasm Diseases 0.000 abstract 1
- 206010014733 Endometrial cancer Diseases 0.000 abstract 1
- 206010014759 Endometrial neoplasm Diseases 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 206010033128 Ovarian cancer Diseases 0.000 abstract 1
- 206010061535 Ovarian neoplasm Diseases 0.000 abstract 1
- 206010060862 Prostate cancer Diseases 0.000 abstract 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 abstract 1
- 208000005718 Stomach Neoplasms Diseases 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 102000015694 estrogen receptors Human genes 0.000 abstract 1
- 108010038795 estrogen receptors Proteins 0.000 abstract 1
- 206010017758 gastric cancer Diseases 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 210000004072 lung Anatomy 0.000 abstract 1
- 230000035772 mutation Effects 0.000 abstract 1
- 201000011549 stomach cancer Diseases 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4741—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Finger-Pressure Massage (AREA)
- Orthopedics, Nursing, And Contraception (AREA)
Abstract
Se proporcionan compuestos de formula (I), donde R1 o R2 se selecciona de Cl, F, -CF3, o -CH3, y el otro es hidrogeno. Son compuestos preferidos: 5-(4-{2-[3-(fluorometil)azetidin-1-il]etoxi}fenil)-8-(trifluorometil)-5H-[1]benzopirano[4,3-c]quinolin-2-ol; 5-(4-{2-[3-(fluorometil)azetidin-1-il]etoxi}fenil)-7-(trifluorometil)-5H-[1]benzopirano[4,3-c]quinolin-2-ol; 8-cloro-5-(4-{2-[3-(fluorometil)azetidin-1-il]etoxi}fenil)-5H-[1]benzopirano[4,3-c]quinolin-2-ol; entre otros. Dichos compuestos son degradadores selectivos del receptor de estrogeno (SERD) y son utiles en el tratamiento de tipos de cancer, tales como cancer de mama, cancer de ovario, cancer de endometrio, cancer de prostata, cancer de utero, cancer gastrico y cancer de pulmon, asi como mutaciones debido a una resistencia emergente.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862697100P | 2018-07-12 | 2018-07-12 | |
| PCT/US2019/041334 WO2020014435A1 (en) | 2018-07-12 | 2019-07-11 | Selective estrogen receptor degraders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20210400A1 true PE20210400A1 (es) | 2021-03-02 |
Family
ID=67470734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2020002017A PE20210400A1 (es) | 2018-07-12 | 2019-07-11 | Degradadores selectivos del receptor de estrogeno |
Country Status (36)
| Country | Link |
|---|---|
| US (4) | US10654866B2 (es) |
| EP (2) | EP4155310A1 (es) |
| JP (4) | JP6995241B2 (es) |
| KR (3) | KR102550538B1 (es) |
| CN (2) | CN112638916B (es) |
| AR (1) | AR115694A1 (es) |
| AU (2) | AU2019299947B2 (es) |
| BR (2) | BR112020025654A2 (es) |
| CA (1) | CA3105501C (es) |
| CL (1) | CL2021000045A1 (es) |
| CO (1) | CO2021000043A2 (es) |
| CR (1) | CR20210007A (es) |
| DK (1) | DK3820873T3 (es) |
| EA (1) | EA202092975A1 (es) |
| EC (1) | ECSP21001770A (es) |
| ES (1) | ES2933980T3 (es) |
| FI (1) | FI3820873T3 (es) |
| HR (1) | HRP20230009T1 (es) |
| HU (1) | HUE060963T2 (es) |
| IL (3) | IL280065B (es) |
| JO (1) | JOP20210005A1 (es) |
| LT (1) | LT3820873T (es) |
| MA (2) | MA53124B1 (es) |
| MD (1) | MD3820873T2 (es) |
| MX (2) | MX2021000375A (es) |
| PE (1) | PE20210400A1 (es) |
| PH (1) | PH12021550049A1 (es) |
| PL (1) | PL3820873T3 (es) |
| PT (1) | PT3820873T (es) |
| RS (1) | RS63809B1 (es) |
| SA (1) | SA521421008B1 (es) |
| SG (1) | SG11202100148TA (es) |
| SI (1) | SI3820873T1 (es) |
| TW (1) | TWI702219B (es) |
| UA (1) | UA127507C2 (es) |
| WO (1) | WO2020014435A1 (es) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL310489A (en) | 2015-10-01 | 2024-03-01 | Olema Pharmaceuticals Inc | Tetrahydro-1H-pyrido[3,4-b]indole anti-estrogenic drugs and preparations containing them for use in cancer treatment |
| PL3820874T3 (pl) * | 2018-07-12 | 2023-02-06 | Eli Lilly And Company | Selektywne środki degradujące receptor estrogenowy |
| TWI702219B (zh) * | 2018-07-12 | 2020-08-21 | 美商美國禮來大藥廠 | 選擇性雌激素受體降解劑 |
| CN114957114A (zh) * | 2021-02-26 | 2022-08-30 | 冷志 | 一种4-溴-3-氯-7-甲氧基喹啉的合成方法 |
| KR20230144571A (ko) | 2021-03-09 | 2023-10-16 | 일라이 릴리 앤드 캄파니 | Serd 투여 요법의 조합을 사용하여 암을 치료하는 방법 |
| TW202300492A (zh) * | 2021-03-16 | 2023-01-01 | 美商美國禮來大藥廠 | 選擇性雌激素受體降解劑 |
| US11926634B2 (en) | 2022-02-01 | 2024-03-12 | Eli Lilly And Company | Processes for the preparation of selective estrogen receptor degraders |
| WO2024083716A1 (en) | 2022-10-17 | 2024-04-25 | Astrazeneca Ab | Combinations of a serd for the treatment of cancer |
| WO2024097206A1 (en) | 2022-11-02 | 2024-05-10 | Petra Pharma Corporation | Allosteric chromenone inhibitors of phosphoinositide 3-kinase (pi3k) for the treatment of disease |
| WO2024100236A1 (en) | 2022-11-11 | 2024-05-16 | Astrazeneca Ab | Combination therapies for the treatment of cancer |
| US20240180893A1 (en) | 2022-11-17 | 2024-06-06 | Astrazeneca Ab | Methods of treatment of breast cancer |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004531562A (ja) * | 2001-05-22 | 2004-10-14 | イーライ・リリー・アンド・カンパニー | ２−置換１，２，３，４−テトラヒドロキノリンおよびその誘導体、組成物ならびに方法 |
| US7329654B2 (en) * | 2001-12-19 | 2008-02-12 | Janssen Pharmaceutica N.V. | Heteroatom containing tetracyclic derivatives as selective estrogen receptor modulators |
| EP1497277A1 (en) * | 2002-04-19 | 2005-01-19 | Signal Pharmaceuticals, Inc. | Benzopyranone compounds, compositions thereof, and methods of treatment therewith |
| US20090023917A1 (en) | 2004-01-22 | 2009-01-22 | Eli Lilly And Company | Selective Estrogen Receptor Modulators for the Treatment of Vasomotor Symptoms |
| US20080221163A1 (en) * | 2005-01-18 | 2008-09-11 | Jeffrey Alan Dodge | Selective Estrogen Receptor Modulators |
| EP3010502B1 (en) | 2013-06-19 | 2018-11-21 | Seragon Pharmaceuticals, Inc. | Azetidine estrogen receptor modulators and uses thereof |
| CN107406424B (zh) * | 2014-12-18 | 2020-08-25 | 豪夫迈·罗氏有限公司 | 雌激素受体调节剂及其用途 |
| JP6679147B2 (ja) * | 2014-12-18 | 2020-04-15 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | テトラヒドロ−ピリド［３，４−ｂ］インドールエストロゲン受容体モジュレーター及びその使用 |
| WO2018108954A1 (en) | 2016-12-12 | 2018-06-21 | F. Hoffmann-La Roche Ag | Process for the preparation of 2-(3-(fluoromethyl)azetidin-1-yl)ethan-1-ol |
| PL3820874T3 (pl) * | 2018-07-12 | 2023-02-06 | Eli Lilly And Company | Selektywne środki degradujące receptor estrogenowy |
| TWI702219B (zh) * | 2018-07-12 | 2020-08-21 | 美商美國禮來大藥廠 | 選擇性雌激素受體降解劑 |
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2019
- 2019-07-02 TW TW108123257A patent/TWI702219B/zh active
- 2019-07-03 AR ARP190101886A patent/AR115694A1/es unknown
- 2019-07-11 CA CA3105501A patent/CA3105501C/en active Active
- 2019-07-11 MA MA53124A patent/MA53124B1/fr unknown
- 2019-07-11 MX MX2021000375A patent/MX2021000375A/es unknown
- 2019-07-11 KR KR1020217000466A patent/KR102550538B1/ko active IP Right Grant
- 2019-07-11 MD MDE20210462T patent/MD3820873T2/ro unknown
- 2019-07-11 EP EP22201995.2A patent/EP4155310A1/en active Pending
- 2019-07-11 KR KR1020227044200A patent/KR102589886B1/ko active IP Right Grant
- 2019-07-11 RS RS20221142A patent/RS63809B1/sr unknown
- 2019-07-11 LT LTEPPCT/US2019/041334T patent/LT3820873T/lt unknown
- 2019-07-11 CN CN201980046849.3A patent/CN112638916B/zh active Active
- 2019-07-11 PT PT197459258T patent/PT3820873T/pt unknown
- 2019-07-11 SG SG11202100148TA patent/SG11202100148TA/en unknown
- 2019-07-11 ES ES19745925T patent/ES2933980T3/es active Active
- 2019-07-11 BR BR112020025654-4A patent/BR112020025654A2/pt unknown
- 2019-07-11 KR KR1020237034781A patent/KR20230148386A/ko not_active Application Discontinuation
- 2019-07-11 EA EA202092975A patent/EA202092975A1/ru unknown
- 2019-07-11 FI FIEP19745925.8T patent/FI3820873T3/fi active
- 2019-07-11 US US16/508,745 patent/US10654866B2/en active Active
- 2019-07-11 PE PE2020002017A patent/PE20210400A1/es unknown
- 2019-07-11 UA UAA202100102A patent/UA127507C2/uk unknown
- 2019-07-11 PL PL19745925.8T patent/PL3820873T3/pl unknown
- 2019-07-11 DK DK19745925.8T patent/DK3820873T3/da active
- 2019-07-11 CN CN202311312431.7A patent/CN117379428A/zh active Pending
- 2019-07-11 JP JP2021500536A patent/JP6995241B2/ja active Active
- 2019-07-11 CR CR20210007A patent/CR20210007A/es unknown
- 2019-07-11 BR BR122023025061-3A patent/BR122023025061A2/pt unknown
- 2019-07-11 SI SI201930406T patent/SI3820873T1/sl unknown
- 2019-07-11 MA MA53126A patent/MA53126B1/fr unknown
- 2019-07-11 WO PCT/US2019/041334 patent/WO2020014435A1/en unknown
- 2019-07-11 AU AU2019299947A patent/AU2019299947B2/en active Active
- 2019-07-11 HU HUE19745925A patent/HUE060963T2/hu unknown
- 2019-07-11 JO JOP/2021/0005A patent/JOP20210005A1/ar unknown
- 2019-07-11 HR HRP20230009TT patent/HRP20230009T1/hr unknown
- 2019-07-11 EP EP19745925.8A patent/EP3820873B1/en active Active
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2020
- 2020-05-18 US US16/876,819 patent/US11117902B2/en active Active
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2021
- 2021-01-06 CO CONC2021/0000043A patent/CO2021000043A2/es unknown
- 2021-01-07 CL CL2021000045A patent/CL2021000045A1/es unknown
- 2021-01-08 PH PH12021550049A patent/PH12021550049A1/en unknown
- 2021-01-10 IL IL280065A patent/IL280065B/en unknown
- 2021-01-11 MX MX2023006047A patent/MX2023006047A/es unknown
- 2021-01-12 SA SA521421008A patent/SA521421008B1/ar unknown
- 2021-01-12 EC ECSENADI20211770A patent/ECSP21001770A/es unknown
- 2021-09-02 US US17/465,066 patent/US11634426B2/en active Active
- 2021-12-14 JP JP2021202668A patent/JP7009672B1/ja active Active
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2022
- 2022-01-12 JP JP2022003022A patent/JP7241211B2/ja active Active
- 2022-01-16 IL IL289871A patent/IL289871B2/en unknown
- 2022-06-08 AU AU2022203969A patent/AU2022203969B2/en active Active
- 2022-08-14 IL IL295598A patent/IL295598B2/en unknown
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2023
- 2023-03-06 JP JP2023033486A patent/JP2023081954A/ja active Pending
- 2023-03-15 US US18/121,667 patent/US11993608B2/en active Active
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