Design and synthesis of a cocaine-diamide hapten for vaccine development
A cocaine-diamide hapten was designed in an effort to obtain a potent, long-lasting anti-cocaine immune response for the treatment of cocaine abuse. The analogue 3 incorporated two amido linker functionalities was synthesized in 6 chemical steps starting from (+)-2-carbomethoxy-3-tropinone.
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Cited by (22)
Calix[n]arene-based immunogens: A new non-proteic strategy for anti-cocaine vaccine
2022, Journal of Advanced ResearchCitation Excerpt :Amine 11 was prepared in 98% yield by the protection of the commercially available 6-aminohexanoic acid (10) with benzyl alcohol [74], while the benzoylecgonine (13) was furnished in its salt form (Scheme 2 - panel B) in 84% yield from the chemoselectivity hydrolysis of the methyl ester of cocaine (12) [75] (Scheme 2 - panel A). Subsequently, the carboxylic acid group of 13 was coupled with amine 11, in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), furnishing amide 14 in 71% yield [44] (Scheme 2 - panel A). The benzyl ester group of 14 was then reductively cleaved by treatment with H2 and Pd/C to provide the hapten GNE in 52% overall yield (3 steps) from cocaine (12) [51] (Scheme 2 - panel A).
Vaccination against cocaine using a modifiable dendrimer nanoparticle platform
2020, VaccineCitation Excerpt :This substitution increases the capacity to hydrogen bond to antibodies [31], and increases humoral stability by removing a structurally labile esterase site thereby reducing degradation into cocaine metabolites. GNE was chosen as the PDD conjugate rather than cocaine or the analogs GNC or GND per se because this analog has an increased serum half-life and generates antibodies in greater concentration, leading to a greater immunogenicity and therefore cocaine sequestering ability [31–33]. PDD also increases the immunogenicity of GNE due to the presence of 2–3 PADRE molecules per dendrimer that target PDD to cells expressing MHC class II molecules on their surface, including APC cells necessary to process antigen for presentation and mount an effective antibody response (Fig. 1B).
Synthesis of C-3 alkyl analogs of cocaine
2001, Tetrahedron LettersSynthesis of enantiopure aza-analogues of cocaine
1997, Tetrahedron LettersAnti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?
2023, Journal of Medicinal Chemistry