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US 12,252,477 B2Granted
Applications of known and novel cannabinoids
AssigneeBessor Pharma, LLC
InventorsBarry A. Berkowitz, Anthony G. Barrett, Daniel Elliott
Life of this patent
Estimating the term…
Abstract
The use of a medicament as a single agent, binary agent, or other combination comprising of substantially pure novel cannabinoids 1 and 2, optionally admixed with one or more known and novel cannabinoids and other known naturally occurring and synthetic tetracyclic 2A and tricyclic 1A cannabinoids for the prevention, treatment or cure of inflammatory mediated diseases or inflammatory mediated pathological conditions, anorexia, arthritis, cancer, pain, glaucoma, migraine, persistent muscle spasms, seizures (epileptic seizures), severe nausea, PTSD, autism spectrum disorder, drug abuse, insomnia, or any other chronic or persistent medical symptom.
Claims20
A method of preventing, treating or curing an inflammatory mediated disease or inflammatory mediated pathological condition of one or more from the group consisting of the central or peripheral nervous system, cardiovascular-renal system, skin, gastrointestinal system, pulmonary-respiratory system, endocrine system, joints, musculo-skeletal system, blood or lymph system, genitourinary system, eye, and ear or for the prevention, treatment or cure of one or more of anorexia, arthritis, cancer, pain, glaucoma, migraine, persistent muscle spasms in an individual or animal in need of treatment and seizures, in an individual or animal in need of treatment comprising administering a medicament as single agent, binary agent, or other combination to the individual or animal, the medicament comprising
- (a) one or more cannabinoids of the formulae 1 or 2;
- (b) pharmaceutically acceptable excipients,
- wherein formula 1 is:
- wherein:
- RB is selected from the group consisting of H or C1 to C2 alkyl, linear or branched C3 to C10 alkyl or double branched C4 to C10 alkyl, in each case optionally substituted by one or two hydroxyl groups or optionally substituted by one or more fluoro-groups, (CH2)o—C3 to C6 cycloalkyl, (CH2)p—ORF, and C3 to C6 cycloalkyl optionally substituted by a C1 to C8 alkyl;
- o is an integer 0-6;
- p is an integer 1-6;
- and
- R1 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- and RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- and
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl or 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- and
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is CONHRD or CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently 0, 1, 2, 3, 4, 5 or 6;
- and
- wherein formula 2 is:
- wherein:
- RB is selected from the group consisting of H, C1 to C2 alkyl, linear or branched C3 to C10 alkyl and double branched C4 to C10 alkyl, in each case optionally substituted by one or two hydroxyl groups or optionally substituted by one or more fluoro-groups, (CH2)o—C3 to C6 cycloalkyl, (CH2)p—ORF, and C3 to C6 cycloalkyl optionally substituted by a C1 to C8 alkyl;
- is an integer 0-6;
- p is an integer 1-6;
- and
- R1 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl or 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 or CH(CH3)2;
- RA is CONHRD or CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- each r is independently an integer 0-6.
106 more elements
A method of preventing, treating or curing an affliction in an individual or animal that is treatable by affecting one or more from the group consisting of cannabinoid receptors, serotonin receptors, ion channels, Toll like receptors, opioid receptors, NMDA or excitatory amino acids receptors, catecholamine receptors enzymes regulating endocannabinoids comprising administering a medicament as single agent, binary agent, or other combination to the individual or animal, the medicament comprising
- (a) one or more cannabinoids of the formulae 1 or 2;
- and
- (b) pharmaceutically acceptable excipients,
- wherein formula 1 is:
- wherein:
- RB is selected from the group consisting of H or C1 to C2 alkyl, linear or branched C3 to C10 alkyl or double branched C4 to C10 alkyl, in each case optionally substituted by one or two hydroxyl groups or optionally substituted by one or more fluoro-groups, (CH2)o—C3 to C6 cycloalkyl, (CH2)p—ORF, and C3 to C6 cycloalkyl optionally substituted by a C1 to C8 alkyl;
- o is an integer 0-6;
- p is an integer 1-6;
- and
- R1 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- and RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- and
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- and
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is CONHRD or CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently 0, 1, 2, 3, 4, 5 or 6;
- wherein formula 2 is:
- wherein:
- RB is selected from the group consisting of H, C1 to C2 alkyl, linear or branched C3 to C10 alkyl and double branched C4 to C10 alkyl, in each case optionally substituted by one or two hydroxyl groups or optionally substituted by one or more fluoro-groups, (CH2)o—C3 to C6 cycloalkyl, (CH2)p—ORF, and C3 to C6 cycloalkyl optionally substituted by a C1 to C8 alkyl;
- is an integer 0-6;
- p is an integer 1-6;
- and
- R1 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of C2 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2;
- RA is selected from the group consisting of H, CO2H and its pharmaceutically acceptable salts, CO2RC, CONHRD, and CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, C8 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6;
- or wherein:
- R1 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- R2 is selected from the group consisting of H, C1 to C6 alkyl, (CH2)n—C3 to C6 cycloalkyl, and (CH2)m—OR3;
- each n is independently an integer 0-2;
- each m is independently 1 or 2;
- R3 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3 or CH(CH3)2;
- RA is CONHRD or CONRDRE;
- RC is selected from the group consisting of C1 to C6 alkyl, (CH2)q—C3 to C6 cycloalkyl, C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- q is an integer 0-6;
- RD is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- RE is selected from the group consisting of C1 to C6 alkyl, (CH2)r—C3 to C6 cycloalkyl, allyl, benzyl, substituted benzyl and 2-phenylethyl;
- or
- NRDRE is selected from the group consisting of azetidinyl, pyrrolidinyl, morpholinyl and piperidinyl, each optionally substituted by one or two hydroxyl groups or hydroxymethyl groups, with the proviso that the hydroxyl groups cannot be on the carbon bearing the heterocyclic ring nitrogen or the heterocyclic ring oxygen with morpholine;
- RF is C1 to C6 alkyl or (CH2)r—C3 to C6 cycloalkyl;
- and
- each r is independently an integer 0-6.
107 more elements
Dependencies are inferred from the claim text.