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WO2025174912A1 - Promédicaments alcoxy-carbonyloxy-alkyle et alkylcarbonyloxy-alkyle de tamiflu - Google Patents

Promédicaments alcoxy-carbonyloxy-alkyle et alkylcarbonyloxy-alkyle de tamiflu

Info

Publication number
WO2025174912A1
WO2025174912A1 PCT/US2025/015636 US2025015636W WO2025174912A1 WO 2025174912 A1 WO2025174912 A1 WO 2025174912A1 US 2025015636 W US2025015636 W US 2025015636W WO 2025174912 A1 WO2025174912 A1 WO 2025174912A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
pharmaceutically acceptable
influenza
acceptable salt
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
PCT/US2025/015636
Other languages
English (en)
Inventor
Eugene J. Eisenberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Promedy LLC
Original Assignee
Promedy LLC
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 Promedy LLC filed Critical Promedy LLC
Publication of WO2025174912A1 publication Critical patent/WO2025174912A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/52—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • OCEE molecular weight of 312 Daltons, calculated log P of 2.1, and a topological polar surface area (TPSA) of 91
  • TPSA topological polar surface area
  • OCEE causes central suppression of respiratory function in rats, and thus may be associated with the rare events of sudden death observed in influenza patients after taking OCEE.
  • Interactions with GABA-A, GABA-B, NMDA and their related receptors/channels, including Na + and Ca 2+ , channels are thought to be potentially related to respiratory suppression followed by psychotic reactions (both acute 2 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT and chronic) and sudden death.
  • the of Formula I is a of Formula I-1: wherein R 1 is hydrogen or methyl; and 5 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No.
  • the compound of Formula I is a compound of Formula I-1B: or a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof.
  • a compound of Formula II which can be as a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof; wherein R 1 is hydrogen or methyl.
  • pharmaceutical compositions comprising a compound of Formula I, Formula IA, Formula II, or Formula IB, or a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof, in a pharmaceutically acceptable carrier, excipient, or diluent.
  • FIG.1 is a pharmacokinetic profile of oseltamivir carboxylate (OC) and Compound 2 in plasma following administration an oral dose of Compound 2 in dogs described in Example 2.
  • OC oseltamivir carboxylate
  • FIG.1 is a pharmacokinetic profile of oseltamivir carboxylate (OC) and Compound 2 in plasma following administration an oral dose of Compound 2 in dogs described in Example 2.
  • DETAILED DESCRIPTION Compounds of Formula I [0022] Provided herein are compounds of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, or a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof.
  • R 1 is hydrogen.
  • R 1 is methyl.
  • R 2 is O-C3-10cycloalkyl substituted with R 5 . In one embodiment of Formula I-1, including any of the foregoing, R 2 is unsubstituted C 1-6 alkyl. [0024] In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, including any of the foregoing, R 2 is C2-4alkyl, C3-8cycloalkyl, O-C1-3alkyl, or O-C3- 8 cycloalkyl.
  • R 2 is n-propyl or iso-propyl. In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, including any of the foregoing, R 2 is n-butyl, sec-butyl, t-butyl, or iso-butyl. In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, including any of the foregoing, R 2 8 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No.
  • DMPK100PCT is n-pentyl, iso-pentyl, or neo-pentyl.
  • R 2 is n-hexyl, iso-hexyl, or neo-hexyl.
  • R 2 is O-methyl.
  • R 2 is O-ethyl.
  • R 2 is cyclobutyl. In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I- 1B, R 2 is cyclopentyl. In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, R 2 is cyclohexyl. In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, R 2 is cycloheptyl. In one embodiment of Formula I, Formula I-1, Formula I-1A, or Formula I-1B, R 2 is cyclooctyl.
  • R 3 is -C(O)NH2. In one embodiment of Formula I, Formula I- 1A, or Formula I-1B, including any of the foregoing, R 3 is -NHC(O)NH2. In one embodiment of Formula I, Formula I-1A, or Formula I-1B, including any of the foregoing, R 3 is -SO 2 NH 2 . In one embodiment of Formula I, Formula I-1A, or Formula I-1B, including any of the foregoing, R 3 is -OC(O)NH2. In one embodiment of Formula I, Formula I-1A, or Formula I- 1B, including any of the foregoing, R 3 is .
  • R 5 is C1-3alkyl. In one embodiment of Formula I, Formula I-1A, or Formula I-1B, including any of the foregoing, R 5 is halogen. In one embodiment of Formula I, Formula I-1A, or Formula I-1B, including any of the foregoing, R 5 is hydroxy. In one embodiment of Formula I, Formula I-1A, or Formula I-1B, including any of the foregoing, R 5 is amino. In one embodiment of Formula I, Formula I-1A, or Formula I-1B, including any of the foregoing, R 5 is cyano.
  • the compound of Formula II is or a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof.
  • the compound of Formula II is or a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof.
  • the compound of Formula II, or a pharmaceutically acceptable salt thereof is about 85% to about 95% free of other stereoisomers based solely on the weight of the compound of Formula II. In one embodiment, the compound of Formula II, or a pharmaceutically acceptable salt thereof, is about 95% to about 100% free of other stereoisomers based solely on the weight of the compound of Formula II.
  • Definitions [0041] When referring to the compounds and compositions provided herein, the following terms have the following meanings unless indicated otherwise. Unless defined otherwise, all 14 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art.
  • alkoxy refers to the group OR wherein R is alkyl as defined herein.
  • amino refers to -NH 2 . 15 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT
  • cyano refers to -CN.
  • cycloalkyl refers to a monocyclic or polycyclic saturated carbocyclic ring.
  • Monocyclic carbocycles have 3 to 8 ring atoms or in some embodiments, 5 or 6 ring atoms.
  • Bicyclic carbocycles have 7 to 12 ring atoms, e.g., arranged as a bicyclo [4,5], [5,5], [5,6] or [6,6] system, or 9 or 10 ring atoms arranged as a bicyclo [5,6] or [6,6] system, or spiro-fused rings.
  • amino acid sidechain refers to a D- or L- natural or non- naturally occurring amino acid sidechain.
  • Non-limiting representative amino acid sidechains include, but are not limited to those in the following amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamic acid, glutamine, glycine, phenylalanine, histidine, isoleucine, lysine, leucine, methionine, proline, serine, threonine, valine, tryptophan, and tyrosine.
  • the amino acid sidechain is the L-amino acid sidechain.
  • subject refers to an animal, such as a mammal including a non- primate (e.g., a cow, pig, horse, cat, dog, rat, and mouse) and a primate (e.g., a monkey such as a cynomolgous monkey, a chimpanzee, and a human), and in certain embodiments, a human.
  • a non- primate e.g., a cow, pig, horse, cat, dog, rat, and mouse
  • a primate e.g., a monkey such as a cynomolgous monkey, a chimpanzee, and a human
  • the subject is a farm animal (e.g., a horse, a cow, a pig, etc.) or a pet (e.g., a dog or a cat).
  • the subject is a human.
  • DMPK100PCT understood that the compound can have one or more pharmaceutically acceptable salts associated with it.
  • pharmaceutically acceptable acid addition salts include those formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; as well as organic acids such as acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2 hydroxyethanesulfonic acid, benzenesulfonic acid,
  • the term “isolated” with respect to a composition refers to a composition that includes at least 85%, 90%, 95%, 98%, or 99% to 100% by weight, of a specified compound alone (i.e., excluding the weight of a pharmaceutically acceptable salt, if the compound exists as a pharmaceutically acceptable salt), the remainder comprising other chemical species or stereoisomers based on the weight of the specified compound alone (i.e., excluding the weight of a pharmaceutically acceptable salt, if the compound exists as a pharmaceutically acceptable salt).
  • a prodrug or dual prodrug described herein which constitutes a “therapeutically effective amount” will vary depending on the compound, the influenza infection and its severity, the age of the patient to be treated, and the 18 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT like.
  • the therapeutically effective amount can be determined routinely by one of ordinary skill in the art having regard to their knowledge and to this disclosure.
  • the terms “therapeutic agent” and “therapeutic agents” refer to any agent(s) which can be used in the treatment of an influenza infection or one or more symptoms thereof.
  • the term “therapeutic agent” includes a compound provided herein.
  • a therapeutic agent is an agent that is known to be useful for, or has been or is currently being used for the treatment of influenza or one or more symptoms thereof.
  • “Treating” or “treatment” of influenza includes (i) preventing the influenza from occurring in a human, i.e., causing the clinical symptoms of the influenza not to develop in an animal that may be exposed to or predisposed to the influenza, but does not yet experience or display symptoms of the influenza; (ii) inhibiting the influenza infection, i.e., arresting its development and/or its replication; and (iii) relieving influenza, e.g., relieving or reducing a symptom thereof.
  • Treating” or “treatment” of influenza refers, in certain embodiments, to ameliorating influenza that exists in a subject.
  • “treating” or “treatment” includes ameliorating at least one physical parameter, which may be indiscernible in the subject, for example, viral load.
  • “treating” or “treatment” includes modulating influenza, either physically (e.g., stabilization of a discernible symptom) or physiologically (e.g., stabilization of a physical parameter) or both.
  • “treating” or “treatment” includes delaying the onset of the influenza.
  • “Preventing” or “prevent” of an influenza infection includes the administration of a compound as described herein to reduce the likelihood of an occurrence or reoccurrence of the influenza infection, or to minimize a new influenza infection relative to an influenza infection that would have occurred without such treatment.
  • prevention includes administering a compound as described herein to a host who has been exposed to and is thus at risk of contracting an influenza infection.
  • the terms “prophylactic agent” and “prophylactic agents” refer to any agent(s) which can be used in the prevention of an influenza infection, or one or more symptoms thereof.
  • the term “prophylactic agent” includes a compound as provided herein. In certain other embodiments, the term “prophylactic agent” does not refer 19 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT a compound provided herein.
  • a prophylactic agent can be an agent that is known to be useful for, or has been or is currently being used to prevent or impede the onset, development, progression, and/or severity of influenza/an influenza infection.
  • prophylactically effective amount refers to the amount of a therapy (e.g., prophylactic agent) which is sufficient to result in the prevention or reduction of the development, recurrence or onset of one or more symptoms associated with an influenza infection, or to enhance or improve the prophylactic effect(s) of another therapy (e.g., another prophylactic agent).
  • a therapy e.g., prophylactic agent
  • Methods of Treatment Provided herein is a method to treat influenza comprising administering a compound of Formula I, Formula II, Formula IA, or Formula IB, or a pharmaceutically acceptable salt thereof and/or a stereoisomer or mixture of stereoisomers thereof, to a patient in need thereof.
  • the method is for inhibiting an influenza infection.
  • the method is for relieving influenza. In one embodiment, the method is for the prevention of an influenza infection. In one embodiment, the influenza virus is type A. In one embodiment, the influenza virus is type B. In one embodiment, the patient is a human, and in a further embodiment, the patient is an adolescent (a human between the ages of about 10 and 19 years). In one embodiment, the patient is a human less than about 13 years of age. In one embodiment, the patient is a human less than about one year of age.
  • Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water can be used as a carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Examples of suitable pharmaceutical carriers are described in Remington: The Science and Practice of Pharmacy; Pharmaceutical Press; 22 edition (September 15, 2012). 21 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No.
  • compositions and dosage forms will contain a prophylactically or therapeutically effective amount of a prophylactic or therapeutic agent, in certain embodiments, in purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the subject.
  • the formulation should suit the mode of administration.
  • the pharmaceutical compositions or single unit 22 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT dosage forms are sterile and in suitable form for administration to a subject, in certain embodiments, an animal subject, such as a mammalian subject, in certain embodiments, a human subject.
  • a pharmaceutical composition is formulated to be compatible with its intended route of administration.
  • dosage forms include, but are not limited to: tablets; caplets; capsules, such as soft elastic gelatin capsules; cachets; troches; lozenges; dispersions; suppositories; ointments; cataplasms (poultices); pastes; powders; dressings; creams; plasters; solutions; patches; aerosols (e.g., nasal sprays or inhalers); gels; liquid dosage forms suitable for oral or mucosal administration to a subject, including suspensions (e.g., aqueous or non- aqueous liquid suspensions, oil in water emulsions, or a water in oil liquid emulsions), solutions, and elixirs; liquid dosage forms suitable for parenteral administration to a subject; and sterile solids (e.g., crystalline or amorphous solids) that can be reconstituted to provide liquid dosage forms suitable for parenteral administration to a subject.
  • suspensions e.g., aqueous or non-
  • the composition is a liquid composition for oral administration, including, but not limited to, a suspension, emulsion, syrup, or elixir containing inert diluents, such as water or liquid paraffin. These compositions can also comprise substances other than diluents, for example, wetting, sweetening or flavoring products.
  • Pharmaceutical compositions that are suitable for oral administration can be presented as discrete dosage forms, such as, but are not limited to, tablets (e.g., chewable tablets), caplets, capsules, and liquids (e.g., flavored syrups). Such dosage forms contain predetermined amounts of active ingredients, and may be prepared by methods of pharmacy well known to those skilled in the art.
  • Lubricants that can be used in pharmaceutical compositions and dosage forms include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oil (e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil), zinc stearate, ethyl oleate, ethyl laureate, agar, and mixtures thereof.
  • hydrogenated vegetable oil e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil
  • zinc stearate ethyl oleate, ethyl laureate, agar, and mixtures thereof.
  • Additional lubricants include, in certain embodiments, a syloid silica gel (AEROSIL 200, manufactured by W.R. Grace Co. of Baltimore, MD), a coagulated aerosol of synthetic silica (marketed by Degussa Co. of Plano, TX), CAB O SIL (a pyrogenic silicon dioxide product sold by Cabot Co. of Boston, MA), and mixtures thereof. If used at all, lubricants are typically used in an amount of less than about 1 weight percent of the pharmaceutical compositions or dosage forms into which they are incorporated. [0095]
  • the composition can also be suitable for parenteral administration.
  • the compositions for parenteral administration can be emulsions or sterile solutions.
  • Parenteral dosage forms can be administered to subjects by various routes including, but not limited to, subcutaneous, intravenous (including bolus injection), intramuscular, and intra-arterial. Because their administration typically bypasses subjects’ natural defenses against contaminants, parenteral dosage forms are typically, sterile or capable of being sterilized prior to administration to a subject.
  • parenteral dosage forms include, but are 26 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions.
  • compositions can also be formulated for inhalation.
  • Formulations suitable for inhalation can be delivered by a wide range of passive breath driven and active power driven single/-multiple dose dry powder inhalers (DPI).
  • DPI dry powder inhalers
  • the devices most commonly used for respiratory delivery include nebulizers, metered- dose inhalers, and dry powder inhalers.
  • nebulizers Several types are available, including jet nebulizers, ultrasonic nebulizers, and vibrating mesh nebulizers.
  • compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active principle, excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.
  • excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.
  • the ingredients of compositions are supplied either separately or mixed together in unit dosage form, in certain embodiments, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachet indicating the quantity of active agent.
  • the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline.
  • Analytical HPLC was performed on Agilent 1200 HPLC with a Zorbax Eclipse XDB C18 column (2.1 x 150 mm) with flow rate of 1 mL/min.
  • Mobile phase A 0.1% of TFA in water
  • mobile phase B 0.1% of TFA in acetonitrile.
  • a generic gradient method was used.
  • Preparative HPLC was performed on Varian ProStar using Hamilton C18 PRP-1 column (15 x 250 mm) with flow rate of 20 mL/min.
  • Mobile phase A 0.1% of TFA in water; mobile phase B: 0.1% of TFA in acetonitrile.
  • a generic gradient method was used. 28 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No.
  • Step 2 Synthesis of Compound 1-3: To a solution of compound 1-2 (1.8 g, 4.36 mmol, 1 eq) in THF (25 mL) was treated with aq. NaOH (5N, 13 mL). The resulting reaction mixture was stirred at room temperature overnight. The LC-MS showed the 29 1103806668 ⁇ 2 ⁇ AMERICAS Attorney Ref. No.127531.00010 Client Ref. No. DMPK100PCT reaction was completed. Then the solution was acidified to pH 3 ⁇ 4 with citric acid (6 N).
  • Step 3A Synthesis of Compound 1-5: A mixture of compound 1-3 (3.1 g, 8.1 mmol, 1 eq), compound 1-4 (2.0 g, 12.1 mmol, 1.5 eq) and DIEA (1.6 g, 12.1 mmol,1.5 eq) in CH 3 CN (62 mL) under N 2 was heated to 90 ° C overnight. LC-MS showed the reaction was completed.
  • Step 4A Synthesis of Compound 1: To a solution of compound 1-5 (550 mg, 1.2 mmol, 1.0 eq) in CH 3 CN (11 mL) was added iodotrimethylsilane (260 mg, 1.3 mmol, 1.1 eq).
  • Step 3B Synthesis of Compound 1-7: A mixture of compound 1-3 (3.1 g, 8.1 mmol, 1 eq), compound 1-6 (1.8 g, 12.1 mmol, 1.5 eq) and K2CO3 (2.2 g, 16.2 mmol, 2 eq) in DMF (50 mL) under N 2 was heated to 90 ° C for 1h. LC-MS showed the reaction was completed. The reaction solution was poured into water (150 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford compound 1-7 (1.8 g, 45%) as light-yellow solid.

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  • Health & Medical Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Pulmonology (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • General Health & Medical Sciences (AREA)
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Abstract

La présente invention concerne des promédicaments alcoxy-carbonyloxy-alkyle et alkylcarbonyloxy-alkyle de tamiflu et des compositions pharmaceutiques de ceux-ci utilisés pour le traitement du virus de la grippe.
PCT/US2025/015636 2024-02-12 2025-02-12 Promédicaments alcoxy-carbonyloxy-alkyle et alkylcarbonyloxy-alkyle de tamiflu Pending WO2025174912A1 (fr)

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US63/552,257 2024-02-12

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Citations (3)

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WO2009129305A2 (fr) * 2008-04-15 2009-10-22 Tsrl, Inc. Promédicaments d'inhibiteurs de la neuraminidase
WO2011123856A1 (fr) * 2010-04-02 2011-10-06 Tsrl, Inc. Inhibiteurs de la neuraminidase
WO2022022448A1 (fr) * 2020-07-29 2022-02-03 广州市恒诺康医药科技有限公司 Composé inhibiteur de la neuraminidase, composition pharmaceutique et utilisation de celui-ci

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Publication number Priority date Publication date Assignee Title
WO2009129305A2 (fr) * 2008-04-15 2009-10-22 Tsrl, Inc. Promédicaments d'inhibiteurs de la neuraminidase
WO2011123856A1 (fr) * 2010-04-02 2011-10-06 Tsrl, Inc. Inhibiteurs de la neuraminidase
WO2022022448A1 (fr) * 2020-07-29 2022-02-03 广州市恒诺康医药科技有限公司 Composé inhibiteur de la neuraminidase, composition pharmaceutique et utilisation de celui-ci

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S. M. BERGE ET AL.: "Pharmaceutical Salts", J. PHARM. SCI., vol. 66, 1977, pages 1 - 19, XP002675560, DOI: 10.1002/jps.2600660104
SENGUPTA, P., THE LABORATORY RAT: RELATING ITS AGE WITH HUMAN 'S AMERICAN JOURNAL OF PREVENTIVE MEDICINE, vol. 4, no. 6, 2013
SHIMIZU MAI ET AL: "Systematic Approach for Screening of Prodrugs: Evaluation Using Oseltamivir Analogues as Models", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 110, no. 2, 1 February 2021 (2021-02-01), United States, pages 925 - 934, XP093276602, ISSN: 0022-3549, Retrieved from the Internet <URL:https://dx.doi.org/10.1016/j.xphs.2020.10.018> [retrieved on 20250512], DOI: 10.1016/j.xphs.2020.10.018 *
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