PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Synthesis of N-Aminoalkyl-morphine Structured Haptens

Előadó neve

Simon, Balázs

Előadó munkahelye

Semmelweis University, Department of Pharmaceutical chemistry

Előadó telefonszáma

+36705532589

Előadó e-mail címe

simon.balazs1997@gmail.com

Az előadás címe

Synthesis of N-Aminoalkyl-morphine Structured Haptens

Szerző(k) neve és munkahelye

Balázs Simon
PhD Student, Department of Pharmaceutical Chemistry/Semmelweis University, Budapest

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction
Drug abuse is an ever-growing health, economic and social problem worldwide. Illicit opioid use in the past mainly included heroin but nowadays more and more users abuse prescription opioids such as oxycodone or dihydrocodeine. Therapy exists for the addicts but using the drug during the therapy ruins every achieved result. Moreover relapses are not uncommon that could be deadly. Therefore a more effective alternative therapy is needed: vaccination could be one of these. Small molecules (such as morphine and heroin) are not recognised by the immune system but after structural modifications they can be conjugated to immunogen proteins. After vaccination the immune system will be able to recognise these so-called haptens as an epitope of the protein complex and will produce antibodies against them. The antibody-drug complex cannot cross the blood-brain barrier, which in turn negates its effects in the central nervous system.
Functionalizing opioid molecules at the position of 3-OH, 6-OH and on the nitrogen atom will determine the selectivity of the resulting antibodies.
Aims
Our aim is to synthesize novel morphine-hapten derivatives, especially aminoalkyl side chain containing molecules and confirm their structures with NMR and MS measurements.
Methods
As a first step N-demethylation is needed. For this, 1-chloroethyl-chloroformate can be used. The amino-functionalization can be achieved with haloalkyl-phthalimides and haloalkyl-nitriles. In case of phthalimides the intermediate products have to be hydrolysed (hydrazine, alkaline solution) while the nitrile intermediates have to be reduced.
Result
Currently optimizing the production of intermediates is in progress. N-alkylating with phthalimide derivatives seems to be challenging, therefore alternative synthesis routes have to be considered. One of these could be the introduction of maleimide group that is commonly used in peptide chemistry for conjugation. The reduction of nitrile derivatives is also a challenging task, hence reagents such as SmI2 have to be tested.
Conclusion
Opioid haptens could and should be really useful tools against opioid addiction but effectively functionalizing them is a complex and troublesome task.
Funding
No external funding was received.

simon.balazs1997@gmail.com
Semmelweis University, Doctoral School of Pharmaceutical Sciences
Supervisor: Dr. Sándor Hosztafi

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Sándor Hosztafi

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6898

Start

11:15

End

11:20

Authors (legacy)

Balázs Simon
PhD Student, Department of Pharmaceutical Chemistry/Semmelweis University, Budapest