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US 2017/0362195 A1Published application
Methods for the manufacture of cannabinoid prodrugs, pharmaceutical formulations and their use
AssigneeFull Spectrum Laboratories Limited
InventorsRichard C. Peet, Malcolm J. Kavarana
Life of this patent
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Abstract
Described are methods for producing cannabinoid prodrugs as well as methods for formulating such prodrugs in a pharmaceutically acceptable form and their use as therapeutic agents for treating diseases.
Claims20
A method for producing a cannabinoid prodrug of Formula Ia or Formula IIa:
- comprising the step of contacting a compound according to Formula I or Formula II
- with an activated —Y—Z reagent to produce a prodrug according to Formula Ia or Formula IIa;
- wherein,
- R is —H;
- R1 is —H, —COOH, or —COO(C1-C5)alkyl;
- R2 is selected from the group consisting of (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkylalkylene, (C3-C10)aryl, and (C3-C10)arylalkylene;
- R3 is —H, or (C1-C5)alkyl;
- Z is selected from the group consisting of hemisuccinate, succinate, -oxalate, C(O)—CH2—[OCH2CH2]n—OR4, —C(O)—CH2—[OCH2CH2]n—NH2, —C(O)[CH2]n—NR4R5, —C(O)O[CH2]n—NR4R5, —C(O)—NH—[CH2]n—NR4R5, —C(O)[CH2]n—N+(R4)(R5))(R6)X−, —C(O)O[CH2]n—N+(R4)(R5)(R6)X−, —C(O)—NH—[CH2]n—N+(R4)(R5))(R6)X−, and -oligosaccharide;
- Y is selected from the group consisting of L-amino acid residue, a D-amino acid residue, a β-amino acid residue, a γ-amino acid residue, —C(O)—CH2—[OCH2CH2]n—O—, and —C(O)—CH2—[OCH2CH2]n—NH—;
- or —Y—Z is an oligosaccharide;
- R4, R5, and R6 are each independently selected from the group consisting of —H, —OH, formyl, acetyl, pivaloyl, and (C1-C5)alkyl;
- “n” is 1, 2, 3, 4, 5, or 6;
- and
- “X” is a counter ion derived from a pharmaceutically acceptable acid.
11 more elements
A method for producing a cannabinoid prodrug of Formula IVa or Formula Va:
- comprising
- (a) contacting a compound of Formula VI:
- with a cannabinoid synthase to obtain a compound according to Formula IV or Formula V:
- and
- (b) contacting the compound according to Formula IV or Formula V with an activated —Z reagent to obtain the Formula IVa or Formula Va compound;
- wherein
- R7 is —H, —COOH, or —COO(C1-C5)alkyl;
- R8 is selected from the group consisting of (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkylalkylene, (C3-C10)aryl, and (C3-C10)arylalkylene;
- R9 is —H, or (C1-C5)alkyl;
- Y is selected from the group consisting of L-amino acid residue, a D-amino acid residue, a β-amino acid residue, a γ-amino acid residue, and —C(O)—CH2—[OCH2CH2]n—NH—;
- Z is selected from the group consisting of hemisuccinate, succinate, oxalate, —C(O)—CH2—[OCH2CH2]n—OR10, —C(O)—CH2—[OCH2CH2]n—NH2, —C(O)[CH2]n—NR10R11, —C(O)O[CH2]n—NR10R11, —C(O)—NH—[CH2]n—NR10R11, —C(O)[CH2]n—N+(R10)(R11))(R12)X−, —C(O)O[CH2]n—N+(R10)(R11)(R12)X−, and —C(O)—NH—[CH2]n—N+(R10)(R11))(R12)X−,
- R10, R11, and R12 are each independently selected from the group consisting of —H, —OH, formyl, acetyl, pivaloyl, and (C1-C5)alkyl;
- “n” is 1, 2, 3, 4, 5, or 6;
- and
- “X” is a counter ion derived from a pharmaceutically acceptable acid.
12 more elements
A method for producing a cannabinoid prodrug of Formula VIIa or Formula VIIIa:
- comprising
- (a) contacting a compound of Formula IX:
- with a cannabinoid synthase to obtain the Formula VIIa or Formula VIIIa compound;
- wherein
- R13 is —H, —COOH, or —COO(C1-C5)alkyl;
- R14 is selected from the group consisting of (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkylalkylene, (C3-C10)aryl, and (C3-C10)arylalkylene;
- R15 is —H, or (C1-C5)alkyl;
- —Y is selected from the group consisting of L-amino acid residue, a D-amino acid residue, a β-amino acid residue, a γ-amino acid residue, —C(O)—CH2—[OCH2CH2]n—O—, and —C(O)—CH2—[OCH2CH2]n—NH—;
- —Z is selected from the group consisting of hemisuccinate, succinate, oxalate, —C(O)—CH2—[OCH2CH2]n—OR4, —C(O)—CH2—[OCH2CH2]n—NH2, —C(O)[CH2]n—NR16R17, —C(O)O[CH2]n—NR16R17, —C(O)—NH—[CH2]n—NR16R17, —C(O)[CH2]n—N+(R16)(R17))(R18)X−, —C(O)O[CH2]n—N+(R16)(R17)(R18)X−, and —C(O)—NH—[CH2]n—N+(R16)(R17))(R18)X−, wherein
- R16, R17, and R18 are each independently selected from the group consisting of —H, —OH, formyl, acetyl, pivaloyl, and (C1-C5)alkyl;
- “n” is 1, 2, 3, 4, 5, or 6;
- and
- “X” is a counter ion derived from a pharmaceutically acceptable acid.
10 more elements
Dependencies are inferred from the claim text.