PE20200837A1 - Compuestos macrociclicos derivados de diazaciclononadeca [1,2,3-c/d] indenos inhibidores de la proteina de diferenciacion celular de leucemia mieloide inducida (mcl-1) y composiciones farmaceuticas que los comprenden - Google Patents
Compuestos macrociclicos derivados de diazaciclononadeca [1,2,3-c/d] indenos inhibidores de la proteina de diferenciacion celular de leucemia mieloide inducida (mcl-1) y composiciones farmaceuticas que los comprendenInfo
- Publication number
- PE20200837A1 PE20200837A1 PE2020000240A PE2020000240A PE20200837A1 PE 20200837 A1 PE20200837 A1 PE 20200837A1 PE 2020000240 A PE2020000240 A PE 2020000240A PE 2020000240 A PE2020000240 A PE 2020000240A PE 20200837 A1 PE20200837 A1 PE 20200837A1
- Authority
- PE
- Peru
- Prior art keywords
- diazacyclononadeca
- mcl
- alkyl
- myeloid leukemia
- cell differentiation
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/16—Peri-condensed systems
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07D491/12—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 three hetero rings
- C07D491/18—Bridged systems
-
- 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
- C07D491/22—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 four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Referido a un compuesto de formula I, o una sal aceptable desde el punto de vista farmaceutico de este, en donde A2 es CR2; A3 es N; A4 es CR4a y A6 C; o A2 es Cr2, A3 es N, A4 es O o S, y A6 es C; o A2 es N , A3 es C, A4 O o S y A6 es C, entre otros; RA es H, CH3, halogeno, CN, entre otros; X es O, o N(Rx2); Y es (CH2)m, -CH=CH-(CH2)n-, -(CH2)p-CH=CH- o -(CH2)q-CH=CH-(CH2)r- , entre otros; m es 2, 3, 4 o 5; n es 1, 2 o 3; p es 1, 2 o 3; q es 1 o 2; y r es 1 o 2; en donde la suma de q y r es 2 o 3; A7 es N o CR7; A8 es N o CR8; A15 es N o CR15; R7, R12 y R16 son cada uno independientemente H, halogeno, C1-C4alquilo, entre otros; R9 es -OH, -O-C1-C4 alquilo, entre otros; R10A y R10B son cada uno independientemente H, C1-C3 alquilo o C1-C3 haloalquilo, entre otros; W es -CH=CH, C1-C4 alquilo, entre otros; R11 es C6-C10 arilo o un heteroarilo de 5-11 miembros, entre otros. Un compuesto preferido es acido (7R,16R)-19,23-dicloro-10-{[2-(4-{[(4S)-2,2-dimetil-1,3-dioxolan-4-il]metoxi}fenil)pirimidin-4-il]metoxi}-1-(4-fluorofenil)-20,22-dimetil-16-[(4-metilpiperazin-1-il)metil]-7,8,15,16-tetrahidro-18,21 -eteno-13,9-(meteno)-6,14,17-trioxa-2-tia-3,5-diazaciclononadeca[1,2,3-cd]inden-7-carboxilico. Estos compuestos son inhibidores macrociclicos de la proteina de diferenciacion celular de leucemia mieloide inducido (MCL-1). Tambien se refiere a metodo de sintesis de compuestos intermediarios y a un metodo para tratar mieloma multiple.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762545853P | 2017-08-15 | 2017-08-15 | |
| US201762555475P | 2017-09-07 | 2017-09-07 | |
| US201862692663P | 2018-06-30 | 2018-06-30 | |
| PCT/US2018/000180 WO2019035911A1 (en) | 2017-08-15 | 2018-08-15 | MACROCYCLIC INHIBITORS OF MCL-1 AND METHODS OF USE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20200837A1 true PE20200837A1 (es) | 2020-08-13 |
Family
ID=65362347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2020000240A PE20200837A1 (es) | 2017-08-15 | 2018-08-15 | Compuestos macrociclicos derivados de diazaciclononadeca [1,2,3-c/d] indenos inhibidores de la proteina de diferenciacion celular de leucemia mieloide inducida (mcl-1) y composiciones farmaceuticas que los comprenden |
Country Status (22)
| Country | Link |
|---|---|
| US (4) | US10676485B2 (es) |
| EP (2) | EP3988555A1 (es) |
| JP (1) | JP2020531433A (es) |
| KR (1) | KR20200041942A (es) |
| CN (1) | CN111818917A (es) |
| AU (1) | AU2018316620A1 (es) |
| BR (1) | BR112020003180A2 (es) |
| CA (1) | CA3073112A1 (es) |
| CL (2) | CL2020000363A1 (es) |
| CO (1) | CO2020002678A2 (es) |
| CR (1) | CR20200124A (es) |
| EC (1) | ECSP20018703A (es) |
| IL (1) | IL272681A (es) |
| MX (1) | MX2020001717A (es) |
| PE (1) | PE20200837A1 (es) |
| PH (1) | PH12020500327A1 (es) |
| RU (1) | RU2020110517A (es) |
| SG (2) | SG10202106345VA (es) |
| TW (1) | TW201920194A (es) |
| UA (1) | UA126586C2 (es) |
| UY (1) | UY37843A (es) |
| WO (1) | WO2019035911A1 (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10202106345VA (en) * | 2017-08-15 | 2021-07-29 | Abbvie Inc | Macrocyclic mcl-1 inhibitors and methods of use |
| AU2018318692A1 (en) * | 2017-08-15 | 2020-03-12 | AbbVie Deutschland GmbH & Co. KG | Macrocyclic MCL-1 inhibitors and methods of use |
| BR112020003163A2 (pt) * | 2017-08-15 | 2020-09-15 | AbbVie Deutschland GmbH & Co. KG | inibidores macrocíclicos de mcl-1 e métodos de uso |
| TWI796353B (zh) | 2017-08-15 | 2023-03-21 | 美商阿吉歐斯製藥公司 | 丙酮酸激酶調節劑及其用途 |
| CN109467538A (zh) | 2017-09-07 | 2019-03-15 | 和记黄埔医药（上海）有限公司 | 环烯烃取代的杂芳环类化合物及其用途 |
| CA3074641A1 (en) | 2017-09-07 | 2019-03-14 | Augusta University Research Institute, Inc. | Specific akt3 activator and uses thereof |
| UY38700A (es) | 2019-05-20 | 2020-12-31 | Novartis Ag | Conjugados de anticuerpo-fármaco inhibidores de mcl-1 y sus métodos de uso |
| US20240042051A1 (en) | 2020-11-24 | 2024-02-08 | Francesca Rocchetti | Mcl-1 inhibitor antibody-drug conjugates and methods of use |
| WO2022261310A1 (en) | 2021-06-11 | 2022-12-15 | Gilead Sciences, Inc. | Combination mcl-1 inhibitors with anti-body drug conjugates |
| CN117651554A (zh) | 2021-06-11 | 2024-03-05 | 吉利德科学公司 | Mcl-1抑制剂与抗癌剂的组合 |
| WO2023225359A1 (en) | 2022-05-20 | 2023-11-23 | Novartis Ag | Antibody-drug conjugates of antineoplastic compounds and methods of use thereof |
| WO2025111450A1 (en) | 2023-11-22 | 2025-05-30 | Les Laboratoires Servier | Anti-cd74 antibody-drug conjugates and methods of use thereof |
| WO2025111431A1 (en) | 2023-11-22 | 2025-05-30 | Les Laboratoires Servier | Anti-cd7 antibody-drug conjugates and methods of use thereof |
| TW202530255A (zh) | 2023-12-15 | 2025-08-01 | 法商亞維西亞有限公司 | 抗ｉｌ－１ｒａｐ結合結構域及其抗體－藥物偶聯物 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009134658A2 (en) * | 2008-04-30 | 2009-11-05 | National Health Research Institutes | Fused bicyclic pyrimidine compounds as aurora kinase inhibitors |
| FR3015483B1 (fr) * | 2013-12-23 | 2016-01-01 | Servier Lab | Nouveaux derives de thienopyrimidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JO3474B1 (ar) * | 2014-08-29 | 2020-07-05 | Amgen Inc | مشتقات تيتراهيدرونافثالين التي تثبط بروتين mcl-1 |
| FR3037957B1 (fr) | 2015-06-23 | 2019-01-25 | Les Laboratoires Servier | Nouveaux derives d'hydroxyester, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3037958B1 (fr) | 2015-06-23 | 2019-01-25 | Les Laboratoires Servier | Nouveaux derives d'hydroxy-acide, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3037956B1 (fr) | 2015-06-23 | 2017-08-04 | Servier Lab | Nouveaux derives d'acide amine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3037959B1 (fr) | 2015-06-23 | 2017-08-04 | Servier Lab | Nouveaux derives bicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3046792B1 (fr) | 2016-01-19 | 2018-02-02 | Les Laboratoires Servier | Nouveaux derives d'ammonium, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| MX386103B (es) | 2016-04-22 | 2025-03-18 | Astrazeneca Ab | Inhibidores de mcl-1 y metodos de uso de los mismos. |
| AU2017300738A1 (en) | 2016-07-22 | 2019-02-07 | Les Laboratoires Servier | Combination of a BCL-2 inhibitor and a MCL-1 inhibitor, uses and pharmaceutical compositions thereof |
| RS63400B1 (sr) | 2016-10-28 | 2022-08-31 | Servier Lab | Lipozomska formulacija za upotrebu u lečenju kancera |
| WO2018126898A1 (zh) | 2017-01-05 | 2018-07-12 | 河南美泰宝生物制药有限公司 | 噻吩并嘧啶衍生物、其制备方法及在制备抗肿瘤药物中的应用 |
| UY37560A (es) | 2017-01-06 | 2018-07-31 | Servier Lab | Combinación de un inhibidor de mcl-1 y un compuesto taxano, usos y composiciones farmacéuticas de ésta |
| SG10202106345VA (en) * | 2017-08-15 | 2021-07-29 | Abbvie Inc | Macrocyclic mcl-1 inhibitors and methods of use |
| BR112020003163A2 (pt) * | 2017-08-15 | 2020-09-15 | AbbVie Deutschland GmbH & Co. KG | inibidores macrocíclicos de mcl-1 e métodos de uso |
| AU2018318692A1 (en) * | 2017-08-15 | 2020-03-12 | AbbVie Deutschland GmbH & Co. KG | Macrocyclic MCL-1 inhibitors and methods of use |
| CN107573360B (zh) | 2017-10-27 | 2019-08-09 | 都创(上海)医药科技有限公司 | 一种多靶点小分子化合物s63845的制备方法 |
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2018
- 2018-08-15 SG SG10202106345VA patent/SG10202106345VA/en unknown
- 2018-08-15 US US15/998,789 patent/US10676485B2/en active Active
- 2018-08-15 PE PE2020000240A patent/PE20200837A1/es unknown
- 2018-08-15 BR BR112020003180-1A patent/BR112020003180A2/pt not_active IP Right Cessation
- 2018-08-15 CR CR20200124A patent/CR20200124A/es unknown
- 2018-08-15 UA UAA202001749A patent/UA126586C2/uk unknown
- 2018-08-15 RU RU2020110517A patent/RU2020110517A/ru unknown
- 2018-08-15 EP EP21197248.4A patent/EP3988555A1/en active Pending
- 2018-08-15 KR KR1020207007568A patent/KR20200041942A/ko not_active Ceased
- 2018-08-15 UY UY0001037843A patent/UY37843A/es not_active Application Discontinuation
- 2018-08-15 CA CA3073112A patent/CA3073112A1/en active Pending
- 2018-08-15 WO PCT/US2018/000180 patent/WO2019035911A1/en not_active Ceased
- 2018-08-15 JP JP2020508463A patent/JP2020531433A/ja active Pending
- 2018-08-15 SG SG11202001182QA patent/SG11202001182QA/en unknown
- 2018-08-15 TW TW107128523A patent/TW201920194A/zh unknown
- 2018-08-15 AU AU2018316620A patent/AU2018316620A1/en not_active Abandoned
- 2018-08-15 MX MX2020001717A patent/MX2020001717A/es unknown
- 2018-08-15 EP EP18846737.7A patent/EP3652184A1/en not_active Withdrawn
- 2018-08-15 CN CN201880066986.9A patent/CN111818917A/zh active Pending
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2020
- 2020-02-12 CL CL2020000363A patent/CL2020000363A1/es unknown
- 2020-02-13 PH PH12020500327A patent/PH12020500327A1/en unknown
- 2020-02-14 IL IL272681A patent/IL272681A/en unknown
- 2020-03-10 CO CONC2020/0002678A patent/CO2020002678A2/es unknown
- 2020-03-13 EC ECSENADI202018703A patent/ECSP20018703A/es unknown
- 2020-05-11 US US16/872,279 patent/US20200325153A1/en not_active Abandoned
- 2020-11-12 CL CL2020002943A patent/CL2020002943A1/es unknown
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2022
- 2022-02-03 US US17/649,906 patent/US20230183261A1/en not_active Abandoned
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2024
- 2024-02-29 US US18/592,020 patent/US20250092062A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA3073112A1 (en) | 2019-02-21 |
| US20250092062A1 (en) | 2025-03-20 |
| CL2020000363A1 (es) | 2020-06-12 |
| UY37843A (es) | 2019-03-29 |
| US10676485B2 (en) | 2020-06-09 |
| MX2020001717A (es) | 2020-10-08 |
| KR20200041942A (ko) | 2020-04-22 |
| UA126586C2 (uk) | 2022-11-02 |
| RU2020110517A3 (es) | 2022-03-23 |
| US20200325153A1 (en) | 2020-10-15 |
| AU2018316620A1 (en) | 2020-03-12 |
| SG10202106345VA (en) | 2021-07-29 |
| IL272681A (en) | 2020-03-31 |
| RU2020110517A (ru) | 2021-09-16 |
| BR112020003180A2 (pt) | 2020-09-15 |
| CN111818917A (zh) | 2020-10-23 |
| PH12020500327A1 (en) | 2020-10-12 |
| CR20200124A (es) | 2020-09-28 |
| EP3652184A4 (en) | 2020-05-20 |
| CO2020002678A2 (es) | 2020-08-10 |
| US20230183261A1 (en) | 2023-06-15 |
| EP3988555A1 (en) | 2022-04-27 |
| CL2020002943A1 (es) | 2021-03-12 |
| ECSP20018703A (es) | 2020-04-22 |
| TW201920194A (zh) | 2019-06-01 |
| JP2020531433A (ja) | 2020-11-05 |
| SG11202001182QA (en) | 2020-03-30 |
| EP3652184A1 (en) | 2020-05-20 |
| US20190144465A1 (en) | 2019-05-16 |
| WO2019035911A1 (en) | 2019-02-21 |
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