CU24720B1 - Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer - Google Patents

Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer

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Publication number
CU24720B1
CU24720B1 CU2020000087A CU20200087A CU24720B1 CU 24720 B1 CU24720 B1 CU 24720B1 CU 2020000087 A CU2020000087 A CU 2020000087A CU 20200087 A CU20200087 A CU 20200087A CU 24720 B1 CU24720 B1 CU 24720B1
Authority
CU
Cuba
Prior art keywords
sub
alkylenyl
alkyl
alzheimer
disease
Prior art date
Application number
CU2020000087A
Other languages
English (en)
Other versions
CU20200087A7 (es
Inventor
Cordova Adriana Águila
Martínez Alberto Bencomo
Antela Kathleen Castro-Palomino
Llanos Majel Cervantes
García Orestes De Jesús Díaz
Brown Miriam Doreste
Pupo Laura García
Mesa Leonora González
Chaviano Samila León
Soto Del Valle Roberto Menéndez
Tamayo Laura Otaño
Rol Giselle Pentón
Perera Rafaela Perez
Marrero Suchitil Rivera
Chryslaine Rodríguez-Tanty
Carrazana Marquiza Sablón
Original Assignee
Centro De Neurociencias De Cuba
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Centro De Neurociencias De Cuba filed Critical Centro De Neurociencias De Cuba
Priority to CU2020000087A priority Critical patent/CU24720B1/es
Priority to PCT/CU2021/050012 priority patent/WO2022111742A1/es
Priority to CA3200071A priority patent/CA3200071A1/en
Priority to CN202180091389.3A priority patent/CN116829137A/zh
Priority to AU2021388673A priority patent/AU2021388673A1/en
Priority to MX2023006072A priority patent/MX2023006072A/es
Priority to EP21848149.7A priority patent/EP4252749A1/en
Priority to KR1020237020732A priority patent/KR20230118112A/ko
Priority to US18/038,494 priority patent/US20240299334A1/en
Priority to JP2023531700A priority patent/JP2023551249A/ja
Publication of CU20200087A7 publication Critical patent/CU20200087A7/es
Publication of CU24720B1 publication Critical patent/CU24720B1/es

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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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/0043—Nose
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Psychiatry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Otolaryngology (AREA)
  • Emergency Medicine (AREA)
  • Organic Chemistry (AREA)
  • Hospice & Palliative Care (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Pain & Pain Management (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

<p>Esta invención se relaciona con Ia Química Farmacéutica y se refiere a Ia composición farmacéutica de los compuestos de Fórmula I, los cuales muestran acción multiblanco sobre los sistemas colinérgico, glutamatérgico y mitocondrial que se afectan en Ia Enfermedad de Alzheimer (EA). La formulación de estos compuestos incrementa Ia eficacia y tolerancia mediante su administración por vía oral, sublingual, parenteral, transdérmica y nasal.</p> <p>ESPACIO PARA FÓRMULA</p> <p>donde:<br /> R<sub>1</sub>: -alquilenil-C(O)NH-alquilenil- R<sub>3</sub>, -alquilenil-C(O)O-R<sub>4</sub>;<br /> R<sub>3</sub>: -COOH, -OH, -SH, -NH<sub>2</sub>, -NH-alquilo-, -NH-alquilenil-NH<sub>2</sub>, -NH-alquilenil-NH-<br /> C(O)-alquilenil-S-R<sub>5</sub>, -NH-ditiocarbamato-alquilo, -N-alquilo-ditiocarbamato sales metálicas alcalinotérreas; o sales de los grupos arriba mencionados, farmacéuticamente aceptables.<br /> R<sub>4</sub>: grupo succinimidilo;<br /> R<sub>5</sub>: -H, -C(O)-alquilo, -C(O)-C<sub>6</sub>H<sub>5</sub>; y<br /> R<sub>2</sub>: -H,-alquilo.<br /> El término "alquilo" se caracteriza por ser una cadena alifática lineal o ramificada, de átomos de carbono saturados y átomos de hidrógeno, preferentemente metilo o etilo. El término alquilenil se refiere a un análogo divalente de un grupo alquilo lineal o ramificado, preferentemente metilenil (-CH<sub>2</sub>-), etilenil (-CH<sub>2</sub>CH<sub>2</sub>-) o propilenil (-CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>-).</p> <p> </p> <p><br /> </p> <p> </p> <p> </p>
CU2020000087A 2020-11-24 2020-11-24 Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer CU24720B1 (es)

Priority Applications (10)

Application Number Priority Date Filing Date Title
CU2020000087A CU24720B1 (es) 2020-11-24 2020-11-24 Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer
PCT/CU2021/050012 WO2022111742A1 (es) 2020-11-24 2021-11-18 Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer
CA3200071A CA3200071A1 (en) 2020-11-24 2021-11-18 Pharmaceutical composition of naphthalene derivatives as multi-target therapeutic agents for the treatment of alzheimer's disease
CN202180091389.3A CN116829137A (zh) 2020-11-24 2021-11-18 用于治疗阿尔茨海默氏病的作为多靶标治疗剂的萘衍生物的药物组合物
AU2021388673A AU2021388673A1 (en) 2020-11-24 2021-11-18 Pharmaceutical composition of naphthalene derivatives as multi-target therapeutic agents for the treatment of alzheimer's disease
MX2023006072A MX2023006072A (es) 2020-11-24 2021-11-18 Composicion farmaceutica de derivados de naftaleno como agentes terapeuticos multiblancos para el tratamiento de la enfermedad de alzheimer.
EP21848149.7A EP4252749A1 (en) 2020-11-24 2021-11-18 Pharmaceutical composition of naphthalene derivatives as multi-target therapeutic agents for the treatment of alzheimer's disease
KR1020237020732A KR20230118112A (ko) 2020-11-24 2021-11-18 알츠하이머병의 치료를 위한 다중 표적 치료제로서 나프탈렌 유도체의 약학적 조성물
US18/038,494 US20240299334A1 (en) 2020-11-24 2021-11-18 Pharmaceutical composition of naphthalene derivatives as multi-targeted therapeutic agents for the treatment of alzheimer's disease
JP2023531700A JP2023551249A (ja) 2020-11-24 2021-11-18 アルツハイマー病の治療のためのマルチターゲット治療薬としてのナフタレン誘導体の医薬組成物

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CU2020000087A CU24720B1 (es) 2020-11-24 2020-11-24 Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer

Publications (2)

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CU20200087A7 CU20200087A7 (es) 2022-07-08
CU24720B1 true CU24720B1 (es) 2024-10-09

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CU2020000087A CU24720B1 (es) 2020-11-24 2020-11-24 Composición farmacéutica de derivados de naftaleno como agentes terapéuticos multiblancos para el tratamiento de la enfermedad de alzheimer

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Country Link
US (1) US20240299334A1 (es)
EP (1) EP4252749A1 (es)
JP (1) JP2023551249A (es)
KR (1) KR20230118112A (es)
CN (1) CN116829137A (es)
AU (1) AU2021388673A1 (es)
CA (1) CA3200071A1 (es)
CU (1) CU24720B1 (es)
MX (1) MX2023006072A (es)
WO (1) WO2022111742A1 (es)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119523898A (zh) * 2024-12-02 2025-02-28 肇庆学院 多靶点药物的经鼻给药制剂及其应用

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DE4225730C2 (de) 1992-08-04 2003-04-30 Merz Pharma Gmbh & Co Kgaa Verfahren zur Herstellung von festen Arzneiformkörpern mit protrahierter 2-Stufen-Freisetzung
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CU23844B1 (es) 2009-04-17 2012-10-15 Ct De Neurociencias De Cuba Procedimiento de obtención de nuevos derivados de naftaleno para el diagnóstico in vivo de la enfermedad de alzheimer
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CU24583B1 (es) * 2018-11-06 2022-02-04 Centro De Neurociencias De Cuba Nanopartículas de óxido metálicos conjugados con derivados de naftaleno como agentes de contrastes para la detección de placas amiloides por resonancia magnética (mri)

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CN116829137A (zh) 2023-09-29
CA3200071A1 (en) 2022-06-02
EP4252749A1 (en) 2023-10-04
WO2022111742A1 (es) 2022-06-02
MX2023006072A (es) 2023-06-29
US20240299334A1 (en) 2024-09-12
JP2023551249A (ja) 2023-12-07
KR20230118112A (ko) 2023-08-10
AU2021388673A1 (en) 2024-03-28
CU20200087A7 (es) 2022-07-08
WO2022111742A4 (es) 2022-11-03

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