SEMI-SYNTHETIC CANNABINOL CARBAMATE DERIVATIVE MOLECULES FOR ALZHEIMER'S DISEASE AND THEIR SYNTHESIS METHOD

Abstract

The invention relates to a semi-synthetic cannabinol carbamate derivative molecule for the treatment of Alzheimer's disease and to the synthesis of these molecules.

Description

1 TARIFF SEMI-SYNTHETIC CANNABINOLU FOR ALZHEIMER'S DISEASE CARBAMATE DERIVATIVE MOLECULES AND THE SYNTHESIS METHODS OF THESE MOLECULES TECHNICAL AREA 5 The invention is a semi-synthetic cannabinol carbamate derivative for Alzheimer's disease. It relates to molecules and the synthesis of these molecules. PREVIOUS TECHNIQUE Any cannabinol carbamate derivative drug for Alzheimer's disease 10 The active ingredient is not mentioned. There is currently no available treatment for Alzheimer's. The options are classified into two categories: (i) AChE inhibitors and (ii) NMDA. It is in the form of a receptor antagonist. In Figure 1a-1c, AChE found in the previous technique is shown. inhibitors, and in Figure 1d, the NMDA receptor antagonist found in the previous technique. The synthesized CBN-carbamate derivative molecule, which is the subject of our discovery, was first identified in 1997. It is an alternative to the active ingredient Rivastigmin, which is approved by the FDA. In the Alzheimer's drug treatment mentioned above and given in Figures 1a-1d The low bioavailability of the drugs used, nanomolar formulation before preparation The lack of effectiveness at this level is a deficiency in this context. is being evaluated. 20 THE PURPOSE OF THE INVENTION The aim of the invention is to synthesize CBN (cannabinol), which is found in minor amounts in the hemp plant. A CBN-carbamate derivative of this compound is a biological agent that may be effective in Alzheimer's disease. It involves synthesizing molecules with activity. These active ingredients, which are Alzheimer's drug candidates, are 25 These new synthetic CBN-carbamate derivatives exhibit activity at the nanomolar level. Rivastigmin, which has a carbamate structure, is currently used in the treatment of Alzheimer's disease. It is a potential alternative drug to its active ingredient. LIST OF FIGURES 30 Figure 1a. AChE inhibitor – Donepezil (Previous technique) Figure 1b. AChE inhibitor – Galantamine (Previous technique) Figure 1c. AChE inhibitor – Rivastigmine (Previous technique) Figure 1d NMDA receptor antagonist – Memantine (Previous technique) 2 Figure 2. Synthesis of the molecule related to the invention. DETAILED DESCRIPTION OF THE INVENTION The invention is used in the preparation of drugs to treat Alzheimer's disease. Semi-synthetic cannabinol carbamate derivatives for use and the synthesis of these derivatives 5 It includes. The reaction scheme for the synthesis is given below: The aforementioned synthesis was carried out and the molecule shown in Formula I was 10. CBD (Cannabidiol) isolated from the hemp plant is used to obtain its structure. The compound was used as the starting material for synthesis. In the first step of the synthesis... CBD starting compound in toluene solvent by treatment with iodine (I2). CBN compound was synthesized by boiling. In the second part of the synthesis, secondary amine compounds NaHCO3 (Sodium Bicarbonate) and Triphosgene with CH2Cl2 (methylene chloride) 15 The relevant carbamic chloride derivatives were synthesized by reacting them in the solvent. In the final step of the synthesis, the CBN compound synthesized in the first step, 4-DMAP, is used. (4-Dimethylaminopyridine) and K2CO3 (Potassium Carbonate) with CH3CN (acetonitrile) solvent CBN Carbamate derivatives are obtained by reacting them through boiling. synthesized. 20 CBN is a rare cannabinoid found in trace amounts. Unlike other cannabinoids... CBN, which has a different, unique chemical structure, is among those in the endocannabinoid system. different affinities for receptors in the human body, including It has specificity, which leads to different biological effects in humans. CBN, Although present in very small amounts in the hemp plant, hemp secondary 25 Tetrahydrocannabinol (THC), the main component among its metabolites, interacts with elemental iodine. It can be easily obtained through oxidation. Formula I 3 Alzheimer's disease (AD) is a condition in which memory and other cognitive functions gradually deteriorate with age. Alzheimer's disease is a progressive neurodegenerative disease characterized by a decline in cognitive function. the lack of promising treatments that could cure or modify the disease Therefore, AD has become a major burden worldwide. Currently available Although treatments only provide temporary symptomatic relief, the disease persists for 5 years. Progress continues. To date, there is no effective way to stop or reverse the destruction of neurons. There is no single cure. Existing medications primarily address cognitive impairment typical of AD patients. It alleviates dysfunction. United States Food and Drug Administration The US Food and Drug Administration (USFDA) has currently approved four drugs to treat AD. Their mechanisms of action are detailed in 10 articles. According to, cholinesterase inhibitor (ChEI) and N-methyl-D aspartate (NMDA) receptor antagonist They can be categorized as such. Donepezil is safe and well-tolerated for mild to moderate AD. It has been accepted as a drug. It catalyzes AChE through aromatic π interactions. Galantamine interacts with the anionic zone and the peripheral anionic zone. Rivastigmin is a competitive and reversible inhibitor of AChE and is an alkaloid. It is a new 15-year-old compound. It is a first-generation carbamate derivative and a covalent inhibitor of AChE. Carbamate is originally derived from carbamic acid and is formed by directly absorbing nitrogen (N) and oxygen (O). It is a class of synthetic compounds containing carbonyl compounds linked by a carbamate skeleton. It has demonstrated various pharmacological activities, including anti-AD activity. Rivastigmine is a key carbamate derivative responsible for anticholinesterase activity. It is a pharmacophore. Carbamate derivatives are pseudo-irreversible inhibitors of AChE. It is suggested that AChE interacts with the catalytic anionic region. AChE catalytic The breakdown of carbamate in the region results in amino acid residues, Ser2O3, His447, and Glu334 is cleaved into phenol and carbamylated Ser2O3 residues, respectively, and These ultimately block the ChE region. The compound CBN is a minor cannabinoid 25 Therefore, it has a very limited range of biological activity applications in the literature. Furthermore... CBN carbamate derivatives are unknown in the literature. For all these reasons, the CBN molecule... by creating a carbamate active site on it, as in the Rivastigmin molecule. A similar mechanism of action has been established in Alzheimer's disease. The diversity in CBN carbamate derivatives is due to the 30 atoms attached to the nitrogen (N) atom given in Formula I. This is achieved by having different groups R1 and R2. These groups are distinct from each other. It could be, or it could be the same. Groups R1 and R2 can be derived from at least one of the following structures: 4 • Straight-chain or cyclic hydrocarbons: Alkyl and / or halogen substituents It may include. • Stereochemical variations: Straight-chain or cyclic hydrocarbons Stereochemical isomers or alkyl groups derived from chiral hydrocarbons. • Pyrrolide derivatives: Pyrrolide itself or alkylated, halogenated, esterified, etherified, ketoneized. or pyrrolidines substituted with aryl groups and their chiral derivatives. • Piperidine derivatives: Piperidine itself or in combination with alkyl groups, halogens, esters, ethers, and ketones. or piperidines substituted with aryl groups and their chiral derivatives. • Morpholine derivatives: Morpholine itself or in combination with alkyl groups, halogens, esters, ethers, or ketones. or morpholines substituted with aryl groups and their chiral derivatives. 10 • Benzyl derivatives: The benzyl group itself or an alkyl group at the 2-, 3-, or 4-position. Benzyl groups substituted with halogen, ester, ether, ketone, or aryl groups. • Phenyl derivatives: Derivatives that contain the phenyl group itself or an alkyl group in the 2-, 3-, or 4-position. Phenyl groups substituted with halogen, ester, ether, ketone, or aryl groups. 20 30

Claims

REQUESTS 1. A compound with a formula I structure: (Formula I) 5 2. The synthesis method of the compound according to claim 1, and its characteristic is; • Synthesis of CBD (Cannabidiol) compound isolated from hemp plant its use as a starting material and this compound with iodine (I2) CBN by treatment and boiling in toluene solvent. synthesis of the compound, 10 • CBN compound, secondary amine compounds NaHCO3 (Sodium Bicarbonate) and reacts with triphosgene in CH2Cl2 (methylene chloride) solvent. Synthesis of related carbamic chloride derivatives by keeping them in check, • The CBN compound synthesized in the first step is 4-DMAP (4- Dimethylaminopyridine) and K2CO3 (Potassium Carbonate) with CH3CN 15 reacted by boiling in (acetonitrile) solvent It is characterized by stages of retention.

3. The compound is compliant with claim 1 and its characteristic is that it is a drug to be used in the treatment of Alzheimer's disease. It is characterized by its use in preparation.

4. It is a compound according to claim 1, and its characteristic is that groups R1 and R2 are from the following structures: 20 It is characterized by being derived from at least one of the following: • Straight-chain or cyclic hydrocarbons, • Stereochemical variations, • Pyrrolide derivatives, • Piperidine derivatives, 25 • Morpholine derivatives, • Benzyl derivatives, • Phenyl derivatives.

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