CO2023012903A2 - Derivados de pirimidina útiles como inhibidores de la proteína cinasa de repetición 2 rica en leucina (lrrk2) - Google Patents
Derivados de pirimidina útiles como inhibidores de la proteína cinasa de repetición 2 rica en leucina (lrrk2)Info
- Publication number
- CO2023012903A2 CO2023012903A2 CONC2023/0012903A CO2023012903A CO2023012903A2 CO 2023012903 A2 CO2023012903 A2 CO 2023012903A2 CO 2023012903 A CO2023012903 A CO 2023012903A CO 2023012903 A2 CO2023012903 A2 CO 2023012903A2
- Authority
- CO
- Colombia
- Prior art keywords
- lrrk2
- inhibitors
- leucine
- protein kinase
- pyrimidine derivatives
- Prior art date
Links
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 title 1
- 102000001253 Protein Kinase Human genes 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 4
- 102000009784 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Human genes 0.000 abstract 2
- 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 abstract 2
- 229940043355 kinase inhibitor Drugs 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero 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
- A61K31/495—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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- 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
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Se proporcionan compuestos que tienen actividad como inhibidores de cinasa LRRK2. Los compuestos tienen la Estructura (I): (I) o una sal farmacéuticamente aceptable, estereoisómero o profármaco del mismo, en donde A, B, R1a, R1b, R2 y L son como se definen en la presente. También se proporcionan métodos asociados con la preparación y el uso de estos compuestos, composiciones farmacéuticas que comprenden estos compuestos y métodos para modular la actividad de la cinasa LRRK2.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163164804P | 2021-03-23 | 2021-03-23 | |
PCT/US2022/021573 WO2022204299A1 (en) | 2021-03-23 | 2022-03-23 | Pyrimidine derivatives useful as lrrk2 kinase inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
CO2023012903A2 true CO2023012903A2 (es) | 2023-10-09 |
Family
ID=81328290
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CONC2023/0012903A CO2023012903A2 (es) | 2021-03-23 | 2023-09-28 | Derivados de pirimidina útiles como inhibidores de la proteína cinasa de repetición 2 rica en leucina (lrrk2) |
Country Status (12)
Country | Link |
---|---|
US (3) | US11578061B2 (es) |
EP (1) | EP4313955A1 (es) |
JP (1) | JP2024512024A (es) |
KR (1) | KR20230170684A (es) |
CN (1) | CN117355507A (es) |
AU (1) | AU2022246081A1 (es) |
BR (1) | BR112023019388A2 (es) |
CA (1) | CA3214360A1 (es) |
CO (1) | CO2023012903A2 (es) |
IL (1) | IL306008A (es) |
MX (1) | MX2023011027A (es) |
WO (1) | WO2022204299A1 (es) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11578061B2 (en) * | 2021-03-23 | 2023-02-14 | Halia Therapeutics, Inc. | Inhibitors of LRRK2 kinase |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0619343D0 (en) | 2006-09-30 | 2006-11-08 | Vernalis R&D Ltd | New chemical compounds |
AR074209A1 (es) | 2008-11-24 | 2010-12-29 | Boehringer Ingelheim Int | Derivados de pirimidina utiles para el tratamiento del cancer |
US8735417B2 (en) | 2009-12-17 | 2014-05-27 | Merck Sharp & Dohme Corp. | Aminopyrimidines as Syk inhibitors |
US8759366B2 (en) | 2009-12-17 | 2014-06-24 | Merck Sharp & Dohme Corp. | Aminopyrimidines as SYK inhibitors |
SI2576541T1 (sl) | 2010-06-04 | 2016-07-29 | F. Hoffmann-La Roche Ag | Aminopirimidinski derivati kot modulatorji lrrk2 |
EP3004079B1 (en) | 2013-06-04 | 2018-01-17 | Acturum Real Estate AB | Pyrimidine compounds and their use as gamma secretase modulators |
AU2015210554A1 (en) | 2014-01-29 | 2016-07-07 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
CN104974140B (zh) | 2014-04-14 | 2017-11-24 | 上海海雁医药科技有限公司 | 2,3,4,6‑四取代苯‑1,5‑二胺衍生物、其制法与医药上的用途 |
WO2017087905A1 (en) | 2015-11-20 | 2017-05-26 | Denali Therapeutics Inc. | Compound, compositions, and methods |
US11028080B2 (en) | 2016-03-11 | 2021-06-08 | Denali Therapeutics Inc. | Substituted pyrimidines as LRKK2 inhibitors |
WO2019074810A1 (en) | 2017-10-11 | 2019-04-18 | Merck Sharp & Dohme Corp. | INDAZOLYL-SPIRO [2,3] HEXANE-CARBONITRILE DERIVATIVES AS INHIBITORS OF LRRK2, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF |
TW202017918A (zh) | 2017-12-19 | 2020-05-16 | 美商必治妥美雅史谷比公司 | 作為lpa拮抗劑之環己基酸三唑吖 |
CN110872277B (zh) | 2019-11-14 | 2021-06-04 | 浙江大学 | N-取代芳环-2-氨基嘧啶类化合物及用途 |
US11578061B2 (en) * | 2021-03-23 | 2023-02-14 | Halia Therapeutics, Inc. | Inhibitors of LRRK2 kinase |
-
2022
- 2022-03-23 US US17/702,600 patent/US11578061B2/en active Active
- 2022-03-23 AU AU2022246081A patent/AU2022246081A1/en active Pending
- 2022-03-23 CA CA3214360A patent/CA3214360A1/en active Pending
- 2022-03-23 KR KR1020237035536A patent/KR20230170684A/ko unknown
- 2022-03-23 MX MX2023011027A patent/MX2023011027A/es unknown
- 2022-03-23 BR BR112023019388A patent/BR112023019388A2/pt unknown
- 2022-03-23 WO PCT/US2022/021573 patent/WO2022204299A1/en active Application Filing
- 2022-03-23 JP JP2023558377A patent/JP2024512024A/ja active Pending
- 2022-03-23 EP EP22715927.4A patent/EP4313955A1/en active Pending
- 2022-03-23 IL IL306008A patent/IL306008A/en unknown
- 2022-03-23 CN CN202280036432.0A patent/CN117355507A/zh active Pending
- 2022-12-13 US US18/065,259 patent/US11866423B2/en active Active
-
2023
- 2023-09-28 CO CONC2023/0012903A patent/CO2023012903A2/es unknown
- 2023-11-20 US US18/514,959 patent/US20240190848A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
US20230183217A1 (en) | 2023-06-15 |
IL306008A (en) | 2023-11-01 |
WO2022204299A1 (en) | 2022-09-29 |
MX2023011027A (es) | 2023-09-27 |
US11578061B2 (en) | 2023-02-14 |
AU2022246081A1 (en) | 2023-10-12 |
EP4313955A1 (en) | 2024-02-07 |
JP2024512024A (ja) | 2024-03-18 |
CN117355507A (zh) | 2024-01-05 |
BR112023019388A2 (pt) | 2023-11-07 |
US11866423B2 (en) | 2024-01-09 |
CA3214360A1 (en) | 2022-09-29 |
US20220324845A1 (en) | 2022-10-13 |
US20240190848A1 (en) | 2024-06-13 |
KR20230170684A (ko) | 2023-12-19 |
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