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EP4436559A1 - Composés cannabinoïdes synthétiques, compositions pharmaceutiques et méthodes de traitement - Google Patents

Composés cannabinoïdes synthétiques, compositions pharmaceutiques et méthodes de traitement

Info

Publication number
EP4436559A1
EP4436559A1 EP22899347.3A EP22899347A EP4436559A1 EP 4436559 A1 EP4436559 A1 EP 4436559A1 EP 22899347 A EP22899347 A EP 22899347A EP 4436559 A1 EP4436559 A1 EP 4436559A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
independently selected
group
heteroaryl
aryl
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
EP22899347.3A
Other languages
German (de)
English (en)
Other versions
EP4436559A4 (fr
Inventor
Jonnie R. Williams
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.)
Miralogx LLC
Original Assignee
Miralogx 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 Miralogx LLC filed Critical Miralogx LLC
Publication of EP4436559A1 publication Critical patent/EP4436559A1/fr
Publication of EP4436559A4 publication Critical patent/EP4436559A4/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/94—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such 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
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • 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
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
    • C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
    • C07C217/20—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
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    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/02—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C219/04—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C219/16—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the hydroxy groups esterified by an inorganic acid or a derivative thereof
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    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/02—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C219/18—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and containing rings
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    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/24—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings
    • C07C225/26—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings
    • C07C225/28—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings of non-condensed quinone rings
    • 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
    • C07C233/46—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 an acyclic carbon atom
    • C07C233/47—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 an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/11—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton
    • C07C255/13—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
    • C07C39/17—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings containing other rings in addition to the six-membered aromatic rings, e.g. cyclohexylphenol
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    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/18—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with unsaturation outside the aromatic ring
    • C07C39/19—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with unsaturation outside the aromatic ring containing carbon-to-carbon double bonds but no carbon-to-carbon triple bonds
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    • C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
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    • C07C39/24—Halogenated derivatives
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    • C07C43/14—Unsaturated ethers
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    • C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
    • C07C43/14—Unsaturated ethers
    • C07C43/178—Unsaturated ethers containing hydroxy or O-metal groups
    • C07C43/1788—Unsaturated ethers containing hydroxy or O-metal groups containing six-membered aromatic rings and other rings
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    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
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    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
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    • C—CHEMISTRY; METALLURGY
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    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
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    • C07C49/24—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
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    • C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
    • C07C49/835—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups having unsaturation outside an aromatic ring
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    • C07C50/00—Quinones
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    • C07C59/40—Unsaturated compounds
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    • C07C59/40—Unsaturated compounds
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    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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    • 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
    • C07D405/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
    • C—CHEMISTRY; METALLURGY
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated

Definitions

  • a synthetic cannabinoid derivative has a structure of Formula (I): wherein R 1 and R 2 are each independently selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR A R B , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein R A and R B are each independently selected from hydrogen and C 1-4 alkyl; wherein the aryl or heteroaryl, whether alone or
  • a method of treating a cancer, tumor, addiction, epilepsy, anxiety, or depression comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (I) and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (IA): Formula (IA) wherein R 1 , R 2 , and R 3 are as previously defined.
  • a method of treating a cancer, tumor, addiction, epilepsy, anxiety, or depression comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (IA) and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (II): Formula (II) wherein R 1 , R 2 , R 3 and _________ are as previously defined, or a pharmaceutically acceptable salt or ester thereof.
  • method of treating anxiety, addiction, depression, or Alzheimer’s disease comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (II) and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (II): Formula (IIA) wherein R 1 , R 2 , and R 3 are as previously defined, or a pharmaceutically acceptable salt or ester thereof.
  • method of treating anxiety, addiction, depression, or Alzheimer’s disease comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (IIA) and a pharmaceutically acceptable carrier therefor.
  • a pharmaceutical composition comprises a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (I), (IA), (II), or (IIA), or a combination thereof, and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (III):
  • a method of treating a cancer, tumor, addiction, epilepsy, anxiety, or depression comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (III) and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (IIIA):
  • a method of treating a cancer, tumor, addiction, epilepsy, anxiety, or depression comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (IIIA) and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (IV):
  • method of treating anxiety, addiction, depression, or Alzheimer’s disease comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (IV) and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (IVA): Formula (IVA) wherein R 1 , R 2 , and R 3 are as previously defined, or a pharmaceutically acceptable salt or ester thereof.
  • method of treating anxiety, addiction, depression, or Alzheimer’s disease comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (IVA) and a pharmaceutically acceptable carrier therefor.
  • a pharmaceutical composition comprises a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (III), (IIIA), (IV), or (IVA), or a combination thereof, and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (V): Formula (V) wherein R 1 , R 2 , and R 3 are as previously defined, or a pharmaceutically acceptable salt or ester thereof.
  • a method of treating a cancer, tumor, addiction, epilepsy, anxiety, or depression comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (V) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefor.
  • a synthetic cannabinoid derivative has a structure of Formula (VI): Formula (VI) wherein R 1 , R 2 , and R 3 are as previously defined, or a pharmaceutically acceptable salt or ester thereof.
  • method of treating anxiety, addiction, depression, or Alzheimer’s disease comprises administering to an individual in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (VI) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefor.
  • a pharmaceutical composition comprises a therapeutically effective amount of a synthetic cannabinoid derivative of Formula (V) or Formula (VI) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
  • the compounds disclosed herein can be used in a method of treating diseases and conditions associated with monoamine oxidase (MAO) activity.
  • the individual suffers from depression, pain, or addiction.
  • the method of treating diseases and conditions associated with monoamine oxidase (MAO) activity comprises administering a pharmaceutical composition to an individual in need thereof, wherein the pharmaceutical composition comprises a compound having a structure of Formula (VI):
  • R1 and R2 are each independently selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NRARB, —S-alkyl, —SO-alkyl, —SO2-alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein RA and RB are each independently selected from hydrogen and C1-4 alkyl; wherein the aryl or heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH,
  • the pharmaceutical composition for treating MOA associated diseases or conditions comprises 2,4,4-trimethyl-7-propyl-3,3a,4,9b- tetrahydrocyclopenta[c]chromen-9-ol.
  • the compound disclosed herein comprises: , or a pharmaceutically acceptable salt or ester thereof.
  • the present disclosure relates to a method of treating a sleep disorder, wherein the method comprises administering an effective amount of a compound or pharmaceutical composition disclosed herein.
  • the method of treating a sleep disorder comprises administering one or more of the following compounds to a subject in need thereof: , or a pharmaceutically acceptable salt or ester thereof.
  • FIGURES [30] Figure 1 shows the response curves of increasing concentration of test compound 2,4,4- trimethyl-7-propyl-3,3a,4,9b-tetrahydrocyclopenta[c]chromen-9-ol (T-101, circular symbols) and reference compound R(-)-Deprenyl (square symbols) as indicated on the x-axis. Percentage inhibition of MAO-B is shown on the y-axis.
  • DETAILED DESCRIPTION [31] Cannabinoids produced by the Cannabis sativa plant have the potential to treat a vast assortment of diseases and other human ailments. More than 100 different cannabinoids have been isolated from cannabis and each cannabinoid compound exhibits various effects.
  • THC is well-known for its psychological effects and CBD is known for its non-psychoactive effects.
  • THC and related derivatives typically exert therapeutic activities via cannabinoid receptors found in humans and other mammals.
  • CBD is an isomer of THC.
  • CBD and CBD derivatives also exhibit anti-oxidative and anti-inflammatory effects through pathways not related to cannabinoid receptors.
  • Cannabinoid type 1 (CB 1 ) receptors are found primarily in the brain, including the basal ganglia and in the limbic system, and the hippocampus and the striatum, as well as the cerebellum. CB 1 receptors can be found in the human anterior eye and retina.
  • Cannabis plants that contain high levels of cannabinoids such as THC, for example, are typically known as “marijuana” plants.
  • Cannabis plants with a low cannabinoid content are categorized as “hemp” plants.
  • Individual countries usually determine the levels of cannabinoids that differentiate between cannabis plants that are categorized as marijuana or hemp plants.
  • the THC content on a dry-weight basis for a cannabis plant categorized as a hemp plant is 0.3% or less.
  • Cannabis sativa plants having THC, CBD, and other cannabinoid content levels greater than 0.3% are typically considered marijuana plants.
  • a synthetic cannabinoid derivative has a structure of Formula (I): Formula (I) wherein R 1 and R 2 are each independently selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR A R B , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein R A and R B are each independently selected from hydrogen and C 1-4 alkyl; wherein the
  • a synthetic cannabinoid derivative has a structure of Formula (II): Formula (II) wherein R 1 , R 2 , R 3 and ___ are as previously defined, or a pharmaceutically acceptable salt or ester thereof.
  • a synthetic cannabinoid derivative has a structure of Formula (II):
  • a synthetic cannabinoid derivative has a structure of Formula (V): Formula (V) wherein R 1 and R 2 are each independently selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NR A R B , —S-alkyl, —SO-alkyl, —SO 2 -alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein R A and R B are each independently selected from hydrogen and C 1-4 alkyl; wherein the aryl or heteroaryl, whether alone or
  • a synthetic cannabinoid derivative has the following structure: , or a pharmaceutically acceptable salt or ester thereof.
  • alkyl whether alone or as part of a substituent group, refers to a saturated C1-Cn carbon chain, wherein the carbon chain may be straight or branched; wherein n can be 2, 3, 4, 5, 6, 7, 8, 9 or 10.
  • alkynyl refers to a C 2 -C n , wherein the carbon chain may be straight or branched, wherein the carbon chain contains at least one carbon-carbon triple bond, and wherein n can be 3, 4, 5, 6, 7, 8, 9 or 10.
  • aryl whether alone or as part of a substituent group, refers to an unsubstituted carboxylic aromatic ring comprising between 6 to 14 carbon atoms. Suitable examples include, but are not limited to, phenyl and naphthyl.
  • nitrogen protecting group refers to a group which may be attached to a nitrogen atom to protect said nitrogen atom from participating in a reaction and which may be readily removed following the reaction.
  • acyl refers to a group of the formula —CO—C n wherein C n represent a straight or branched alkyl chain wherein n can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
  • heteroaryl refers to any five or six membered monocyclic aromatic ring structure containing at least one heteroatom selected from the group consisting of O, N and S, and optionally containing one to three additional heteroatoms independently selected from the group consisting of O, N and S; or a nine or ten membered bicyclic aromatic ring structure containing at least one heteroatom selected from the group consisting of O, N and S, and optionally containing one to four additional heteroatoms independently selected from the group consisting of O, N and S.
  • the heteroaryl group may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure.
  • heterocycle groups include, but are not limited to, azetidine, azete, oxetane, oxete, thietane, thiete, diazetidine, diazete, dioxetane, dioxete, dithietane, dithiete, pyrrolidine, pyrrole, tetrahydrofuran, furan, thiolane, thiophene, piperidine, oxane, thiane, pyridine, pyran and thiopyran.
  • the groups described herein can be unsubstituted or substituted, as herein defined.
  • the compounds of the present disclosure may contain at least one hydroxyl group. These at least one hydroxyl group may form an ester with inorganic or organic acid. In particular, pharmaceutically acceptable acids.
  • the ester(s) may form chiral carbons.
  • the present disclosure is directed toward all stereo-chemical forms of the compounds of the present disclosure, including those formed by the formation of one or more ester groups.
  • Non-limiting examples of synthetic cannabinoid derivatives in accordance with the present disclosure [59] Non-limiting examples of synthetic cannabinoid derivatives according to Formulas I, IA, II, and IIA are illustrated below:
  • Non- limiting examples of synthetic cannabinoid derivatives according to Formula V and VI are illustrated below: 5-methyl-2-((1R,5R)-3-methyl-5-(prop-1-en-2-yl)cyclopent-2-en-1-yl)benzene-1,3-diol 2-((1R,5R)-3-methyl-5-(prop-1-en-2-yl)cyclopent-2-en-1-yl)-5-propylbenzene-1,3-diol 5-butyl-2-((1R,5R)-3-methyl-5-(prop-1-en-2-yl)cyclopent-2-en-1-yl)benzene-1,3-diol 2,4-dihydroxy-3-((1R,5R)-3-methyl-5-(prop-1-en-2-yl)cyclopent-2-en-1-yl)-6-pentylbenzoic acid
  • the compounds described herein may be prepared synthetically using known techniques with appropriate modifications to the reactants to form the structures shown herein or by other suitable pathways that will be apparent to persons skilled in the art.
  • compounds described herein may be synthesized according to one or more of the following pathways described in Razdan, Total Synthesis of Cannabinoids, SISA Incorporated, Cambridge, Massachusetts, with appropriate modifications to the reactants, as will be apparent to persons skilled in the art, to yield the structures disclosed herein.
  • the synthesis techniques described in Dialer et al. U.S. Patent 10,059,683 B2 the disclosure of which is hereby incorporated by reference in its entirety, may be suitably adapted to synthesize the cannabinoid derivatives described herein.
  • compounds disclosed herein may also exhibit properties as inhibitors of monoamine oxidase (MAO) activity, including either or both of MAO- A and MAO-B activity. These properties may enable compounds to be effective for treating indications associated with MAO activity, such as depression, pain, a sleep disorder, substance addiction, smoking cessation, and the like.3.
  • the compounds disclosed herein can be used in a method of treating diseases and conditions associated with monoamine oxidase (MAO) activity.
  • the individual suffers from depression, pain, a sleep disorder, or addiction.
  • the method of treating diseases and conditions associated with monoamine oxidase (MAO) activity comprises administering a pharmaceutical composition to an individual in need thereof, wherein the pharmaceutical composition comprises a compound having a structure of Formula (VI): wherein R1 and R2 are each independently selected from the group consisting of H, OH, protected hydroxyl, alkyl, alkenyl, alkynyl, acyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein the alkyl, alkenyl, alkynyl or acyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —OH, alkyl, —O-alkyl, NRARB, —S-alkyl, —SO-alkyl, —SO2-alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycle; wherein RA and RB are each independently selected from
  • the pharmaceutical composition for treating MOA associated diseases or conditions comprises 2,4,4-trimethyl-7-propyl-3,3a,4,9b- tetrahydrocyclopenta[c]chromen-9-ol.
  • Compounds disclosed herein also (or alternatively) may exhibit anti-inflammatory properties owing to the compound’s interaction with inflammation pathways, including by way of example, interleukins such as IL-1 and IL-6, TNF- ⁇ , cyclooxygenase (COX), and the like.
  • a compound’s ability to inhibit MAO-A and/or MAO-B activity, and/or its ability to inhibit COX and/or other pathways associated with inflammation may be evaluated using assays well known to persons of ordinary skill in the art.
  • a cannabinoid derivative as described herein is administered to an individual in need thereof for the treatment of a substance addiction, such as alcohol, tobacco, opioid, prescription drugs, cocaine, benzodiazepines, amphetamines, hallucinogens, inhalants, phencyclidine, or other drug addictions.
  • substance addiction such as alcohol, tobacco, opioid, prescription drugs, cocaine, benzodiazepines, amphetamines, hallucinogens, inhalants, phencyclidine, or other drug addictions.
  • Such treatments also are inclusive of treating withdrawal in dependency on benzodiazepines, opiates, or alcohol, as well as symptoms experienced by patients with substance use disorders, such as anxiety, mood symptoms, pain, and sleep disorders such as insomnia.
  • the cannabinoid derivatives may be effective for treating other types of anxiety disorders, such as post- traumatic stress disorder, general anxiety disorder, panic disorder, social anxiety disorder, and obsessive-compulsive disorder.
  • a cannabinoid derivative as described herein may be administered to an individual in need thereof for the treatment of multiple sclerosis, fibromyalgia, epilepsy or neuropsychiatric disorders that are linked to epilepsy, such as neurodegeneration, neuronal injury, and psychiatric diseases.
  • the cannabinoid derivatives may be effective for potentiating the anticonvulsant activity of other active agents such as phenytoin and diazepam.
  • a cannabinoid derivative as described herein may be used in as an antipsychotic for treating patients with schizophrenia.
  • the cannabinoid derivatives also may be effective to reduce intraocular pressure, such as in the treatment of glaucoma.
  • a cannabinoid derivative as described herein may be administered to an individual in need thereof for the treatment of cancer.
  • the cannabinoid derivative may be effective to block cancer cells from spreading around the body and invading an area entirely; for suppressing the growth of cancer cells and/or promoting the death of cancer cells.
  • the cannabinoid derivatives as described herein may be useful in the treatment of Type 1 diabetes, which is caused by inflammation when the immune system attacks cells in the pancreas; as well as acne, which is caused, in part, by inflammation and overworked sebaceous glands on the body.
  • the anti-inflammatory properties of the compounds may lower the production of sebum that leads to acne, including acne vulgaris, the most common form of acne.
  • the cannabinoid derivatives as described herein may be used to treat Alzheimer’s disease, and particularly to prevent the development of social recognition deficit in subjects when administered in the early stages of Alzheimer’s disease.
  • Other examples of disorders that may be treated by the cannabinoid derivative as described herein include nausea, vomiting, anorexia, and cachexia.
  • the compounds may produce an appetite-enhancing effect, for example in AIDS patients or individuals with Alzheimer’s disease who refuse food.
  • the cannabinoid derivatives as described herein may be useful in the treatment of spasticity caused by multiple sclerosis (MS) or spinal cord injury, movement disorders, such as Tourette’s syndrome, dystonia, or tardive dyskinesia. MS patients may experience benefits on ataxia and reduction of tremors.
  • Analgesic properties of the cannabinoid derivatives may prove beneficial, for example, in the treatment of neuropathic pain due to multiple sclerosis, damage of the brachial plexus and HIV infection, pain in rheumatoid arthritis, cancer pain, headache, menstrual pain, chronic bowel inflammation and neuralgias.
  • the cannabinoid derivatives as described herein may be useful in the treatment of asthma. Experiments examining the anti-asthmatic effect of THC or cannabis date mainly from the 1970s, and are all acute studies.
  • cannabis products may act not only as analgesics but also demonstrate anti-inflammatory potential.
  • some patients employing cannabis report a decrease in their need for steroidal and nonsteroidal anti-inflammatory drugs.
  • Suitable doses may vary over a wide range depending on a variety of factors including the type and/or severity of the disease or disorder, previous treatments, the general health, age, and/or weight of the individual, the frequency of treatments, the rate of release from the composition, and other diseases present. This dose may vary according to factors such as the disease state, age, and weight of the subject. For example, higher doses may be administered for treatments involving conditions that are at an advanced stage and/or life threatening. Dosage regimens also may be adjusted to provide the optimum therapeutic response. [87] Pharmaceutical compositions may be formulated together with one or more acceptable pharmaceutical or food grade carriers or excipients.
  • a composition is provided in an inhaler, which may be actuated to administer a vaporized medium that is inhaled into the lungs.
  • parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, and intracranial injection or infusion techniques. Most often, the pharmaceutical compositions are readily administered orally and ingested.
  • Pharmaceutical compositions may contain any conventional non-toxic pharmaceutically-acceptable carriers, adjuvants or vehicles.
  • the pH of the formulation may be adjusted with acceptable pharmaceutical or food grade acids, bases or buffers to enhance the stability of the formulated composition or its delivery form.
  • Liquid dosage forms for oral administration include acceptable pharmaceutical or food grade emulsions, microemulsions, solutions, suspensions, syrups and elixirs.
  • the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylsulfoxide (DMSO) dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
  • inert diluents commonly used in the art such as, for example, water
  • the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
  • adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
  • the dosage form may also comprise buffering agents.
  • the solid dosage forms of tablets, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract or, optionally, in a delayed or extended manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Tablet formulations for extended release are also described in U.S. Pat. No. 5,942,244.
  • Compositions may contain a cannabinoid derivative or compounds, alone or with other therapeutic compound(s).
  • a therapeutic compound is a compound that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals.
  • a therapeutic compound disclosed herein may be used in the form of a pharmaceutically acceptable salt, solvate, or solvate of a salt, e.g., a hydrochloride. Additionally, therapeutic compound disclosed herein may be provided as racemates, or as individual enantiomers, including the R- or S-enantiomer.
  • the therapeutic compound disclosed herein may comprise a R-enantiomer only, a S-enantiomer only, or a combination of both a R-enantiomer and a S-enantiomer of a therapeutic compound.
  • the therapeutic compound may have anti-inflammatory activity, such as a non-steroidal anti-inflammatory drug (NSAID).
  • NSAIDs are a large group of therapeutic compounds with analgesic, anti-inflammatory, and anti-pyretic properties. NSAIDs reduce inflammation by blocking cyclooxygenase.
  • NSAIDs include, without limitation, aceclofenac, acemetacin, actarit, alcofenac, alminoprofen, amfenac, aloxipirin, aminophenazone, antraphenine, aspirin, azapropazone, benorilate, benoxaprofen, benzydamine, butibufen, celecoxib, chlorthenoxacin, choline salicylate, clometacin, dexketoprofen, diclofenac, diflunisal, emorfazone, epirizole; etodolac, etoricoxib, feclobuzone, felbinac, fenbufen, fenclofenac, flurbiprofen, glafenine, hydroxylethyl salicylate, ibuprofen, indometacin, indoprofen, ketoprofen, ketorolac, lactyl phenet
  • An effective amount may be, e.g., at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day.
  • compositions described herein may be formulated as an elixir, a beverage, a chew, a tablet, a lozenge, a gum, or the like.
  • the pharmaceutical compositions may also be formulated as a pharmaceutically acceptable vehicle such as a capsule, tablet, syrup, lozenge, inhaler, e-cigarette, chewable gum, nasal spray, transdermal patch, liquid, transmucosal vehicle, hydrogel, nanosome, liposome, noisome, nanoparticle, nanosphere, microsphere, microparticle, microemulsion, nanosuspension, or micelle.
  • the compositions may also be formulated, for example, as dietary supplements or nutraceuticals.
  • the reaction mixture was slowly heated to 40 °C and stirred for another 10 min, followed by dropwise addition of a solution of 1-methyl-4-(prop-1-en-2-yl)cyclopent-2-en-1-ol (6.0 g, 138.1 mmol), 5-propylbenzene-1,3-diol (4.6 g, 30 mmol) in anhydrous CH 2 Cl 2 (100 mL).
  • the reaction mixture was stirred at 40 °C for 5 min.
  • the reaction mixture was cooled to room temperature and diluted with saturated NaHCO3 (300 mL) and extracted with CH2Cl2 (300 mL ⁇ 2).
  • the reaction was cooled to 0 °C and quenched with saturated NaHCO 3 solution (100 mL) and extracted with CH 2 Cl 2 (2 ⁇ 100 mL). The combined CH 2 Cl 2 extracts were washed with water (100 mL), brine (100 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated under vacuum to obtain the crude product.
  • the product was purified twice by silica gel chromatography (3-6% EtOAc in hexanes). The fractions containing the pure product were combined and concentrated under reduced pressure to obtain 2,4,4-trimethyl-7-propyl-3,3a,4,9b- tetrahydrocyclopenta[c]chromen-9-ol (086 g, 29 %) as a light brown liquid.
  • Example 2 Monoamine Oxidase Inhibitions
  • MAO-B or MAO-A Monoamine Oxidase
  • the reaction mixture used 100mM potassium phosphate with a pH of 7.4 as incubation buffer.
  • Spectrofluorimetric quantitation of 4-hydroxyquinoline was used to determine activity of the MAO-B or MAO-A enzyme.
  • the assay was performed essentially as described in Biochem Pharmacol.41(2): 155 – 162, and it was performed by Eurofins Panlabs, Inc..
  • IC50 values were determined by a non-linear, least squares regression analysis using MathIQTM (ID Business Solutions Ltd., UK). Where inhibition constants (Ki) are presented, the Ki values were calculated using the equation of Cheng and Prusoff (Cheng, Y., Prusoff, W.H., Biochem. Pharmacol.22:3099-3108, 1973) using the observed IC50 of the tested compound, the concentration of radioligand employed in the assay, and the historical values for the KD of the ligand (obtained experimentally at Eurofins Panlabs, Inc.). Where presented, the Hill coefficient (nH), defining the slope of the competitive binding curve, was calculated using MathIQTM.
  • FIG. 1 shows the response curves of increasing concentration of 2,4,4-trimethyl-7- propyl-3,3a,4,9b-tetrahydrocyclopenta[c]chromen-9-ol (T-101) as indicated on the x- axis and percentage inhibition of MAO-B is shown on the y-axis.
  • T-101 inhibition of MAO-B was determined to be 20.1 ⁇ M.
  • R(-)-Deprenyl inhibition of MAO-B was determined to be 9.69 nM as shown in Figure 1.
  • the tables below show further experimental results. N.C. indicated in the tables means “not calculated.” Table 1 : Experimental results for T-101 and Delta 9-THC

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Abstract

Les dérivés cannabinoïdes peuvent présenter des propriétés anti-inflammatoires, par exemple par l'inhibition des récepteurs cannabinoïdes de type 2 (CB2). Les compositions pharmaceutiques comprenant les dérivés cannabinoïdes peuvent être utilisées pour traiter diverses maladies et états pathologiques chez des mammifères, notamment la douleur, l'anxiété, un trouble du sommeil, l'addiction, l'épilepsie, la dépression ou la maladie d'Alzheimer.
EP22899347.3A 2021-11-27 2022-11-22 Composés cannabinoïdes synthétiques, compositions pharmaceutiques et méthodes de traitement Pending EP4436559A4 (fr)

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