US 12,252,477 B2
Applications of known and novel cannabinoids
Barry A. Berkowitz, Framingham, MA (US); Anthony G. Barrett, Rio de Janeiro (BR); and Daniel Elliott, Basel (CH)
Assigned to Bessor Pharma, LLC, Framingham, MA (US)
Appl. No. 17/269,751
Filed by Bessor Pharma, LLC, Framingham, MA (US)
PCT Filed Aug. 20, 2019, PCT No. PCT/US2019/047284
§ 371(c)(1), (2) Date Feb. 19, 2021,
PCT Pub. No. WO2020/041326, PCT Pub. Date Feb. 27, 2020.
Claims priority of provisional application 62/719,813, filed on Aug. 20, 2018.
Prior Publication US 2021/0236460 A1, Aug. 5, 2021
Int. Cl. C07D 311/78 (2006.01); A61K 31/05 (2006.01); A61K 31/352 (2006.01); C07C 37/50 (2006.01); C07C 37/56 (2006.01); C07C 39/23 (2006.01); C07D 319/08 (2006.01); C07D 493/04 (2006.01)
CPC C07D 311/78 (2013.01) [A61K 31/05 (2013.01); A61K 31/352 (2013.01); C07C 37/50 (2013.01); C07C 37/56 (2013.01); C07C 39/23 (2013.01); C07D 319/08 (2013.01); C07D 493/04 (2013.01); C07C 2601/16 (2017.05)] 20 Claims
OG exemplary drawing
 
1. 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:

OG Complex Work Unit Chemistry
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:

OG Complex Work Unit Chemistry
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.