BR-102024018027-A2 - Development of new ibuprofen derivatives as therapeutic agents for anxiety and seizures.

Abstract

The search for new bioactive compounds capable of exhibiting biological activities for the treatment and prevention of diseases is fundamental to the production of new drugs. This invention consists of a synthesis process for new ibuprofen derivatives, chemically modified to enhance their effects on the central nervous system, aiming to reduce anxiety symptoms and effectively control seizures. The patent details the tests performed to evaluate their efficacy and safety, and the possible mechanisms of action that justify their use in neurological treatments. Furthermore, the patent discusses the advantages of these new derivatives compared to current treatments for anxiety and seizures, such as a lower risk of side effects or greater therapeutic efficacy. In summary, the innovation presented by this patent not only expands the therapeutic possibilities of ibuprofen but also demonstrates a significant advance in the development of new drugs for neurological conditions. With chemically modified derivatives offering potential additional benefits in terms of efficacy and safety, this research opens promising avenues for more effective treatments with fewer side effects for anxiety and seizures. Keywords: Ibuprofen derivatives. Anxiolytics. Anticonvulsants. Chemical synthesis. Central Nervous System.

Inventors

• BENISE FERREIRA DA SILVA
• EMMANUEL SILVA MARINHO
• FRANCISCO ROGÊNIO DA SILVA MENDES
• HELCIO SILVA DOS SANTOS
• JANE EIRE SILVA ALENCAR DE MENEZES
• JÉSSICA BEZERRA MACIEL
• MÁRCIA MACHADO MARINHO
• MARIA KUEIRISLENE AMÂNCIO FERREIRA
• ANTÔNIO WLISSES DA SILVA

Assignees

• FUNDAÇÃO UNIVERSIDADE ESTADUAL DO CEARÁ - FUNECE
• FUNDAÇÃO UNIVERSIDADE ESTADUAL VALE DO ACARAÚ

Dates

Publication Date

20260317

Application Date

20240902

Claims (4)

1. 1. A method for synthesizing ibuprofen derivatives for therapeutic use in the treatment of anxiety and seizures, characterized by the structural modification of ibuprofen through controlled chemical reactions.
2. 2. An ibuprofen-derived compound, as obtained by the method of claim 1, characterized by its specific chemical structure and therapeutic activity in the treatment of anxiety via the serotonergic (SER) pathway.
3. 3. An ibuprofen-derived compound, as obtained by the method of claim 1, characterized by its specific chemical structure and therapeutic activity in the treatment of GABAergic (GABA) seizures.
4. 4. A pharmaceutical composition comprising two ibuprofen derivatives as claimed in claim 2, together with pharmaceutically acceptable excipients, characterized for use in the treatment of anxiety and seizures.

Description

FIELD OF THE INVENTION [01] The present invention falls within the field of pharmacology and medicinal chemistry, more specifically in the development of new therapeutic agents derived from ibuprofen for the treatment of neurological disorders such as anxiety and seizures. The focus of this invention is on the structural modification of ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), to create compounds with enhanced therapeutic properties specific to neurological conditions. [02] Refers to the use of synthesized derivatives from the drug ibuprofen in liquid pharmaceutical formulations or capsules with beneficial effects in the prevention and treatment of anxiety and seizures. [03] The results obtained from this invention are promising, as they demonstrate, through an experimental model, the biological activities with anxiolytic and anticonvulsant action. BACKGROUND OF THE INVENTION [04] Anxiety and seizures are neurological conditions that affect millions of people worldwide. Anxiety is characterized by feelings of fear, worry, and nervousness, while seizures involve abnormal electrical activity in the brain, leading to uncontrollable muscle spasms and, in some cases, loss of consciousness. Both conditions can have a significant impact on patients' quality of life, and effective treatment is crucial for managing symptoms and improving overall well-being. [05] Currently, there are several medications available for the treatment of anxiety and seizures, including benzodiazepines, anticonvulsants, and selective serotonin reuptake inhibitors (SSRIs). However, these treatments often have undesirable side effects, such as excessive sedation, dependence, and tolerance, which limits their long-term effectiveness. Therefore, there is a continuing need to develop new therapeutic agents that offer efficacy in treating these conditions with an improved safety profile. [06] Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely used for the relief of pain, fever and inflammation. Its main action involves the inhibition of cyclooxygenase enzymes (COX-1 and COX-2), which play a key role in the synthesis of prostaglandins, mediators of inflammation. Although ibuprofen is effective in treating inflammatory conditions, its use in treating neurological conditions such as anxiety and seizures has not been fully explored. [07] Recent studies suggest that structural modification of known molecules can lead to the development of new compounds with specific therapeutic activities. In this context, the present invention focuses on the synthesis of ibuprofen derivatives with enhanced therapeutic properties for the treatment of anxiety and seizures. Through controlled chemical modifications, it is possible to obtain new compounds that not only maintain the anti-inflammatory properties of ibuprofen, but also exhibit efficacy in modulating neurological processes associated with anxiety and seizures. [08] Thus, the present invention aims to fill the existing gap in the treatment of these conditions, offering an innovative approach based on ibuprofen derivatives that can provide an effective and safe therapeutic alternative for patients suffering from anxiety and seizures. BRIEF DESCRIPTION OF THE FIGURES Figure 1 - Effect of HYDRAZIDE on the locomotor behavior of adult zebrafish in the Open Field Test (0-5 min). Values represent the mean ± standard error of the mean for 6 animals/group; ANOVA followed by Tukey's test. (****p<0.0001; vs. Control; ##p<0.01, ###p<0.01, ####p<0.0001 vs. DZP). Figure 2A - Anxiolytic effect of HYDRAZIDE in adult zebrafish (Danio rerio) by the Light/Dark Test (0-5 min). Control (DMSO 3%; 20 μL; i.p.); Dzp - Diazepam (1.0 mg/mL; i.p.). Values represent the mean ± standard error of the mean (SEM) for 6 animals/group; ANOVA followed by Tukey's test. (**p<0.01, ****p<0.0001 vs. Control).Figure 2B- Anxiolytic mechanism of action via GABA of HYDRAZIDE (0.1mg/ml) in the Light & Dark Test (0-5min). Vehicle - DMSO 3% (20 μL; i.p.). DZP - Diazepam (1.0 mg/mL; 20 μL; i.p.). Values represent the mean ± standard error of the mean (SEM) for 6 animals/group. ANOVA followed by Tukey (Fmz + DZP, ****p<0.0001 vs. Control).Figure 2C - Anxiolytic mechanism of action via SEROTONINERGIC of HYDRAZIDE (0.1mg/ml). (Danio rerio) adult in the Light & Dark Test (0-5min). Vehicle - DMSO 3% (20 μL; i.p.). DZP - Diazepam (1.0 mg/mL; 20 μL; i.p.). Values represent the mean ± standard error of the mean (SEM) for 6 animals/group. ANOVA followed by Tukey (****p<0.0001, Flx x Flx+ GRAN or PIZ or CIPRO). Figure 3 - Anticonvulsant test of HYDRAZIDE (A) Stage I. (B) Stage II (C) Stage III. (A) Anticonvulsant effect of HYDRAZIDE in adult zebrafish (Danio rerio) from seizure induction by PTZ. Control (DMSO 3%; 20 μL; p.o.); Dzp - Diazepam (1.0 mg/mL; i.p.). The values represent the mean ± standard error of the mean (SEM) for 6 animals/group; ANOVA followed by Tukey. (*p< 0.05, **p< 0.01, ***p< 0.001, ****p< 0.001 vs