Synthesis of tetrahydroquinazoline derivative on the route to possible dual cholinesterase inhibition and antioxidant activity

Other Title(s)

تحضير مشتق تتراهيدروكوينازولين على الطريق المزدوج إلى تثبيط كولين استريز المحتمل و النشاط المضاد للأكسدة

Dissertant

al-Suhaymat, Rawan Ahmad Husayn

Thesis advisor

Abu Diyyah, Ziyad
Abu al-Asal, Qays

University

Isra University

Faculty

Faculty of Pharmacy

University Country

Jordan

Degree

Master

Degree Date

2019

English Abstract

Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorders, expressing a heavy burden on the patient, family, caregivers and society.

While pathological hallmarks of this disorder are known, the exact cause of AD remains unclear.

Unfortunately, the available therapies are only symptomatic, which makes the design and development of new disease-modifying agents a must for the clinical need of millions of patients worldwide.

Quinazoline moiety have been validated as privileged structures with remarkable frameworks for the design and development of Acetylcholinesterase (AChEs) inhibitors.

Also, multiple studies investigated the important role of anti-oxidants and the need for suppressing the reactive oxygen species (ROS) generated in the presence of cell injury in regards to neurodegenerative cells.

Accordingly, several hybrid agents have been synthesized and characterized biochemically as new potential AD treatments, aiming to couple several molecules and capable of attacking multiple aspects of the disease.

Materials and methods: starting from 1-N-Methylisatoic anhydride, novel hydroquinazoline derivative compound 4 {1'-methyl-3', 4'-dihydro-1'H-spiro [cyclopentane-1, 2'-quinazoline]} was synthesized using three steps followed by a coupling process with p-coumaric acid (p-CA) to synthesis the final product compound 5.

Different investigation techniques were utilized for both the monitoring and the characterization of the target products such as thin layer chromatography (TLC), gas–chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) H 1 and C13 .

Results: ammonia aqueous solution (NH4OH) was reacted with the starting material to produce compound 2 giving (87.3 %) yield, through the reaction of this product with cyclopentanone with the aid of toluene-4-sulfonic acid monohydrate (PTSA) as catalyst compound 3 was synthesized (97 %) yield.

Our novel product compound 4 {1'-methyl-3', 4'-dihydro-1'H-spiro [cyclopentane-1, 2'-quinazoline]} was formed through activation of carbonyl carbon of the amide group utilizing trimethylsilyl chloride (TMSCl) followed by a reduction step with lithium aluminum hydride (LiAlH4) ending with (73.3 %) yield.

Conclusion: novel quinazoline derivative compound 4 {1'-methyl-3', 4'-dihydro1'H-spiro [cyclopentane-1, 2'-quinazoline]}, which might be used as cholinesterase inhibitor was synthesized in a good yield (73.3 %).

The structure of the novel synthesized compound was assigned on the bases of GC-MS, H 1 and C13 NMR.

The mass spectra of the synthesized comound showed molecular ions peak at their respective molecular weight, MS, m/z: 204, (tR= 9.5 min) .The NMR spectra of the synthesized compound correlate well with the proposed structure.

Main Topic

Pharmacology

No. of Pages

61

Table of Contents

Table of contents.

Abstract.

Abstract in Arabic.

Chapter One : Introduction.

Chapter Two : Experimental part.

Chapter Three : Results and discussion.

References.

American Psychological Association (APA)

al-Suhaymat, Rawan Ahmad Husayn. (2019). Synthesis of tetrahydroquinazoline derivative on the route to possible dual cholinesterase inhibition and antioxidant activity. (Master's theses Theses and Dissertations Master). Isra University, Jordan
https://search.emarefa.net/detail/BIM-913510

Modern Language Association (MLA)

al-Suhaymat, Rawan Ahmad Husayn. Synthesis of tetrahydroquinazoline derivative on the route to possible dual cholinesterase inhibition and antioxidant activity. (Master's theses Theses and Dissertations Master). Isra University. (2019).
https://search.emarefa.net/detail/BIM-913510

American Medical Association (AMA)

al-Suhaymat, Rawan Ahmad Husayn. (2019). Synthesis of tetrahydroquinazoline derivative on the route to possible dual cholinesterase inhibition and antioxidant activity. (Master's theses Theses and Dissertations Master). Isra University, Jordan
https://search.emarefa.net/detail/BIM-913510

Language

English

Data Type

Arab Theses

Record ID

BIM-913510