AR117539A1 - INHIBIDORES DE TGF-bR1 (ALK5) ÚTILES PARA TRATAR TRASTORNOS DE PROLIFERACIÓN CELULAR - Google Patents
INHIBIDORES DE TGF-bR1 (ALK5) ÚTILES PARA TRATAR TRASTORNOS DE PROLIFERACIÓN CELULARInfo
- Publication number
- AR117539A1 AR117539A1 ARP190103894A ARP190103894A AR117539A1 AR 117539 A1 AR117539 A1 AR 117539A1 AR P190103894 A ARP190103894 A AR P190103894A AR P190103894 A ARP190103894 A AR P190103894A AR 117539 A1 AR117539 A1 AR 117539A1
- Authority
- AR
- Argentina
- Prior art keywords
- membered
- ring
- alkyl
- cycloalkyl
- haloalkoxy
- Prior art date
Links
- 230000004663 cell proliferation Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 4
- 125000005843 halogen group Chemical group 0.000 abstract 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 4
- 229910052799 carbon Inorganic materials 0.000 abstract 3
- 150000004292 cyclic ethers Chemical class 0.000 abstract 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
- 206010016654 Fibrosis Diseases 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 2
- 201000011510 cancer Diseases 0.000 abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- 230000004761 fibrosis Effects 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 125000004076 pyridyl group Chemical group 0.000 abstract 2
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 150000001721 carbon Chemical group 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 210000000056 organ Anatomy 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- 125000003226 pyrazolyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- 125000001425 triazolyl group Chemical group 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La presente está relacionada con compuestos, composiciones y métodos farmacéuticos, especialmente debido a que están relacionados con composiciones y métodos para el tratamiento y/o la prevención de un trastorno de proliferación relacionado con la actividad de TGFbR1, tal como el cáncer o la fibrosis. La misma proporciona compuestos de la fórmula (1) y de la fórmula (2) como se describe con más detalle en la presente que tiene una fracción ácida que realza la especificidad del tejido para los tejidos y los órganos objetivos. La presente incluye composiciones farmacéuticas, combinaciones farmacéuticas y métodos de uso de estos compuestos para tratar afecciones que incluyen el cáncer o la fibrosis. Reivindicación 1: Un compuesto de la fórmula (2), caracterizado porque el anillo A es un anillo heteroaromático con 5 ó 6 miembros que opcionalmente contiene un átomo de nitrógeno adicional como un miembro del anillo y, opcionalmente, está fusionado a un anillo de fenilo o piridinilo, y el anillo A se sustituye opcionalmente por uno o dos grupos independientemente seleccionados de halo, alquilo C₁₋₄, haloalquilo C₁₋₄, alcoxi C₁₋₄, haloalcoxi C₁₋₄, fenilo, piridinilo, un éter cíclico de 4 a 6 miembros y cicloalquilo C₃₋₆; R¹ se selecciona entre CN, alquilo C₁₋₄, haloalquilo C₁₋₄, alcoxi C₁₋₄, haloalcoxi C₁₋₄, cicloalquilo C₃₋₆, heterociclilo de 5 a 6 miembros que contiene N, O ó S como miembro del anillo, fenilo y heteroarilo de 5 a 6 miembros que contiene uno o dos átomos de nitrógeno como miembros del anillo, donde dichos alquilo C₁₋₄, haloalquilo C₁₋₄, alcoxi C₁₋₄, haloalcoxi C₁₋₄, cicloalquilo C₃₋₆, heterociclilo de 5 a 6 miembros, fenilo y heteroarilo de 5 a 6 miembros se sustituyen, cada uno, con uno o dos grupos seleccionados de Q¹; Q¹ se selecciona independientemente en cada ocurrencia de halo, CN, -OH, alquilo C₁₋₄, haloalquilo C₁₋₄, alcoxi C₁₋₄, haloalcoxi C₁₋₄ y cicloalquilo C₃₋₆; L¹ es un conector divalente seleccionado entre -C(R⁹)₂-, -(C(R¹⁰)₂)₂₋₄-, -O-(C(R¹⁰)₂)₁₋₃- y -(C(R¹⁰)₂)ₘ-X-C(R¹⁰)₂)ₙ-; cada R⁹ es independientemente alquilo C₁₋₂ o halo, o dos R⁹ se pueden tomar juntos con el átomo de carbono al que están unidos para formar un anillo de cicloalquilo de 3 a 6 miembros o un éter cíclico de 3 a 6 miembros; R¹⁰ se selecciona de independientemente en cada ocurrencia entre H, F y alquilo C₁₋₄; o dos grupos R¹⁰ en el mismo carbono se pueden tomar junto con el carbono al que están unidos para formar un anillo de cicloalquilo de 3 a 6 miembros o un éter cíclico de 3 a 6 miembros; m es 0, 1 ó 2; n es 0, 1 ó 2; X es un anillo de pirazolil, triazolil o tetrazolil; Z² se selecciona entre CH, CQ² y N; y q es 0 ó 1; Q² se seleccionada de halo, alquilo C₁₋₄, haloalquilo C₁₋₄, alcoxi C₁₋₄ y haloalcoxi C₁₋₄; o una sal farmacéuticamente aceptable de este.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862785616P | 2018-12-27 | 2018-12-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR117539A1 true AR117539A1 (es) | 2021-08-11 |
Family
ID=69185691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP190103894A AR117539A1 (es) | 2018-12-27 | 2019-12-27 | INHIBIDORES DE TGF-bR1 (ALK5) ÚTILES PARA TRATAR TRASTORNOS DE PROLIFERACIÓN CELULAR |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US12102626B2 (es) |
| EP (1) | EP3902796B1 (es) |
| JP (2) | JP7515049B2 (es) |
| KR (1) | KR102832376B1 (es) |
| CN (1) | CN113348167B (es) |
| AR (1) | AR117539A1 (es) |
| AU (1) | AU2019417418B2 (es) |
| BR (1) | BR112021007006A2 (es) |
| CA (1) | CA3117838A1 (es) |
| EA (1) | EA202191619A1 (es) |
| ES (1) | ES2972516T3 (es) |
| IL (1) | IL284266B2 (es) |
| MX (1) | MX2021007738A (es) |
| SG (1) | SG11202103457PA (es) |
| TW (1) | TWI884934B (es) |
| WO (1) | WO2020139636A1 (es) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11730723B2 (en) | 2020-04-21 | 2023-08-22 | Lexicon Pharmaceuticals, Inc. | Compounds and methods for treating viral infections |
| EP4138844A1 (en) | 2020-04-21 | 2023-03-01 | Lexicon Pharmaceuticals, Inc. | 4-(3-(pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine for use in the the treatment of cov-229e or cov-oc43 coronaviruses infections |
| CN113214111A (zh) * | 2021-04-30 | 2021-08-06 | 上海立科化学科技有限公司 | 3-（2-氰基苯基）丙酸及4-氰基-1-茚满酮的制备方法 |
| US12263576B2 (en) | 2021-08-19 | 2025-04-01 | Hyundai Mobis Co., Ltd. | Robot system for automated assembly of modular component |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60221392T2 (de) | 2001-05-24 | 2008-04-17 | Eli Lilly And Co., Indianapolis | Neue pyrrolderivate als pharmazeutische mittel |
| UA80571C2 (en) | 2002-11-22 | 2007-10-10 | Lilly Co Eli | Quinolinyl-pyrrolopyrazoles |
| JPWO2005080377A1 (ja) | 2004-02-20 | 2007-10-25 | キリンホールディングス株式会社 | ＴＧＦβ阻害活性を有する化合物およびそれを含んでなる医薬組成物 |
| WO2009022171A1 (en) | 2007-08-13 | 2009-02-19 | Astrazeneca Ab | Pyridinyiioxy pyridines as alk5 inhibitors |
| US8080568B1 (en) | 2010-06-29 | 2011-12-20 | Ewha University - Industry Collaboration Foundation | 2-pyridyl substituted imidazoles as therapeutic ALK5 and/or ALK4 inhibitors |
| EP2694677A2 (en) | 2011-04-04 | 2014-02-12 | Netherland Cancer Institute | Methods and compositions for predicting resistance to anticancer treatment with protein kinase inhibitors |
| BR112013028430A2 (pt) * | 2011-05-04 | 2017-08-01 | Merck Sharp & Dohme | composto, composição farmacêutica, método para tratar uma doença ou condição mediada por tirosina quinase do baço (syk), e, uso de uma quantidade terapeuticamente eficiente do composto |
| EP2900665B1 (en) * | 2012-09-28 | 2018-01-03 | Merck Sharp & Dohme Corp. | Triazolyl derivatives as syk inhibitors |
| WO2014100314A1 (en) * | 2012-12-21 | 2014-06-26 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors |
| WO2014155300A2 (en) * | 2013-03-28 | 2014-10-02 | Aurigene Discovery Technologies Limited | Substitued pyrimidine amine derivatives as tak-1 inhibitors |
| EP3089971B1 (en) | 2014-01-01 | 2020-07-29 | Medivation Technologies LLC | Compounds and methods of use |
| WO2015157093A1 (en) | 2014-04-08 | 2015-10-15 | Rigel Pharmaceuticals, Inc. | 2,3-disubstituted pyridine compounds as tgf-beta inhibitors and methods of use |
| JO3336B1 (ar) | 2014-10-07 | 2019-03-13 | Lilly Co Eli | مركبات أمينو بيريديلوكسي بيرازول |
| US10702527B2 (en) * | 2015-06-12 | 2020-07-07 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| US10336761B2 (en) | 2015-07-23 | 2019-07-02 | Bristol-Myers Squibb Company | TGFβ receptor antagonist |
| WO2020103817A1 (zh) | 2018-11-20 | 2020-05-28 | 南京圣和药业股份有限公司 | TGF-βR1抑制剂及其应用 |
| KR102816656B1 (ko) | 2019-06-25 | 2025-06-02 | 인벤티스바이오 컴퍼니 리미티드 | 헤테로고리 화합물, 이의 제조방법 및 이의 사용방법 |
| CN112707902B (zh) | 2020-03-23 | 2022-04-15 | 杭州阿诺生物医药科技有限公司 | TGF-β受体抑制剂 |
-
2019
- 2019-12-17 AU AU2019417418A patent/AU2019417418B2/en active Active
- 2019-12-17 WO PCT/US2019/066993 patent/WO2020139636A1/en not_active Ceased
- 2019-12-17 BR BR112021007006-0A patent/BR112021007006A2/pt unknown
- 2019-12-17 EP EP19839715.0A patent/EP3902796B1/en active Active
- 2019-12-17 MX MX2021007738A patent/MX2021007738A/es unknown
- 2019-12-17 US US17/299,696 patent/US12102626B2/en active Active
- 2019-12-17 SG SG11202103457PA patent/SG11202103457PA/en unknown
- 2019-12-17 ES ES19839715T patent/ES2972516T3/es active Active
- 2019-12-17 KR KR1020217021785A patent/KR102832376B1/ko active Active
- 2019-12-17 JP JP2021536757A patent/JP7515049B2/ja active Active
- 2019-12-17 IL IL284266A patent/IL284266B2/en unknown
- 2019-12-17 CA CA3117838A patent/CA3117838A1/en active Pending
- 2019-12-17 EA EA202191619A patent/EA202191619A1/ru unknown
- 2019-12-17 CN CN201980086920.0A patent/CN113348167B/zh active Active
- 2019-12-25 TW TW108147526A patent/TWI884934B/zh active
- 2019-12-27 AR ARP190103894A patent/AR117539A1/es unknown
-
2023
- 2023-01-17 JP JP2023005014A patent/JP2023052437A/ja active Pending
-
2024
- 2024-08-05 US US18/795,000 patent/US20240398776A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| TW202039436A (zh) | 2020-11-01 |
| KR20210110316A (ko) | 2021-09-07 |
| IL284266A (en) | 2021-08-31 |
| JP2022517730A (ja) | 2022-03-10 |
| JP7515049B2 (ja) | 2024-07-12 |
| EP3902796C0 (en) | 2024-02-07 |
| AU2019417418A1 (en) | 2021-04-15 |
| TWI884934B (zh) | 2025-06-01 |
| US12102626B2 (en) | 2024-10-01 |
| EP3902796B1 (en) | 2024-02-07 |
| NZ775362A (en) | 2025-02-28 |
| MX2021007738A (es) | 2021-08-05 |
| IL284266B2 (en) | 2024-06-01 |
| IL284266B1 (en) | 2024-02-01 |
| EA202191619A1 (ru) | 2021-09-28 |
| WO2020139636A1 (en) | 2020-07-02 |
| JP2023052437A (ja) | 2023-04-11 |
| CA3117838A1 (en) | 2020-07-02 |
| KR102832376B1 (ko) | 2025-07-09 |
| CN113348167A (zh) | 2021-09-03 |
| CN113348167B (zh) | 2026-01-09 |
| US20220054465A1 (en) | 2022-02-24 |
| US20240398776A1 (en) | 2024-12-05 |
| ES2972516T3 (es) | 2024-06-13 |
| AU2019417418B2 (en) | 2025-02-27 |
| EP3902796A1 (en) | 2021-11-03 |
| SG11202103457PA (en) | 2021-05-28 |
| BR112021007006A2 (pt) | 2021-08-10 |
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