An in-depth review of thalidomide's basic moieties

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Introduction
Excellent therapeutic advancements against a wide range of ailments, including infectious, metabolic, and cancerous conditions, have been made possible by pharmaceutical innovation.(Ellis Benjamin, 2017) The two heterocyclic ring structures that make up the thalidomide molecule are the alpha or 3′-position of the glutarimide ring and the N-position of the phthalimide ring.It has two enantiomers, the R and S Forms, which have chemically similar structures.(Xiaoping Wang, 2021) S is in charge of the severe birth defects, whilst R exhibits sedative and anti-nausea effects.One 50 mg tablet of thalidomide was sufficient to induce developmental abnormalities.Although the precise cause of thalidomide's teratogenicity is unknown, it is thought to be connected to the drug's disruption of angiogenesis and embryonic development.(Van Derpoorten K, 1997).The tragic history of thalidomide serves as a sobering reminder of how crucial thorough testing and safety assessment are in pharmaceutical chemistry.Thalidomide is classified as a Multi target medication that impacts multiple cellular processes, including as androgen receptor antagonism, peptidase inhibition, cox inhibition, and glucosidase inhibition.There are two ways to make phthalimide.The first approach involves heating phthalic anhydride in the presence of aqueous ammonia to produce phthalimide.The second technique makes use of phthalic anhydride and ammonium carbonate.Ammonium carbonate has a mildly acidic pH.It produces potassium phthalimide when it is made to interact with KOH.
Mechanism of imide formation , through a nucleophilic attack of amino group to anhydride moiety.(Tomoko Asatsuma-Okumura, 2020) Gabriel synthesis, which creates primary amines from phthalimide, is a well-known example of organic synthesis.Primary alkyl halides are converted into primary amines by the Gabriel synthesis.(Duong Binh Minh H., 2019) Gabriel synthesis uses the reagent potassium salt.Phthalimide is sufficiently acidic to react with strong potassium hydroxide solution to produce a potassium salt.For the biological effects of being hypolipidemic, analgesic, anticonvulsant, antiinflammatory, antiviral, antitubercular , and antibacterial, many phthalimide compounds have shown promise.The biological activity of thalidomide, both beneficial and detrimental, is connected to the pthalimide ring.(Benjamin E, 2017) Thalidomide was initially developed as a sedative and anti-nausea drug, but it was later discovered that when used by pregnant women, it causes serious birth abnormalities.Though the precise methods by which thalidomide exerts its effects are complicated and poorly understood, it is thought that the pthalimide ring affects immune system regulation and prevents the release of some inflammatory chemicals.The fact that thalidomide can reduce overactive immune responses makes it effective for treating diseases like leprosy and multiple myeloma.However, thalidomide's teratogenic (birth-defect-causing) effects when taken during pregnancy are also influenced by the same immunemodulating qualities that make it beneficial in some medical diseases.Thalidomide interferes with a fetus' normal growth, resulting in severe defects such limb deformities.Research is still being done to determine the precise interactions that the pthalimide ring in thalidomide has with its biological targets.

Defect Caused by pthalimide ring
The phthalimide ring is the main structural element of thalidomide that causes teratogenicity.The phthalimide ring has a flaw in that it can go through racemization under physiological circumstances, forming both the R and S enantiomers of thalidomide.The desirable sedative effects are caused by one enantiomer, whilst the teratogenic effects are caused by the other enantiomer.This means that one enantiomer, which causes birth abnormalities, is exposed to both enantiomers when a pregnant woman takes thalidomide.Babies born to moms who used thalidomide during pregnancy had significant limb and organ malformations as a result of this stereochemical flaw in the phthalimide ring.Teratogenicity of thalidomide is a coupling response.Later, when additional structural analogues are taken into consideration, the significance of the alpha bond and the chiral nature therefore offered will become clear.Here are a few applications and outcomes connected to the glutarimide ring in thalidomide:  Sedative and Hypnotic: Thalidomide's glutarimide ring contributes to its sedative and hypnotic effects, making it useful for managing sleep disturbances and anxiety. Anti-Nausea: Thalidomide was initially prescribed to pregnant women to alleviate morning sickness due to its anti-nausea properties. Immuno modulatory Effects: Thalidomide's glutarimide ring is associated with its immuno modulatory properties, which have been explored in the treatment of various immune-related disorders, such as leprosy and certain inflammatory diseases.

Conclusion
In conclusion, a detailed analysis of the fundamental molecules of thalidomide exposes the complexity of this medication.The racemic combination of enantiomers that characterizes thalidomide's chiral characteristics is essential to the drug's biological activity and pharmacokinetics.The substance has phthalimide and glutarimide moieties, which are in charge of its sedative and immuno modulatory properties, respectively.Thalidomide is a fascinating case study in the development and regulation of drugs because its history is characterized by both therapeutic success and catastrophic teratogenicity.Its continued medicinal usage and use as a lesson in drug development depend on our ability to comprehend its basic components.Understanding thalidomide's fundamental components is crucial because of the continuous research into its structure-activity correlations and pharmacological mechanisms.
-Isoindole-1,3(2H)-dione) are cyclic imides with the chemical property of having two carbonyl atoms linked to the same nitrogen.(José Guedes da Silva Júnior, 2019) It has the chemical formula C8H5NO2 and is an organic compound.which possesses White Crystalline Solid, which is frequently employed as the first step in the synthesis of organic compounds.(Hayman Sardar Abdulrahman, 2020)The specific uses of the adaptable phthalimide ring can change depending on the intended chemical synthesis or application.(Sanchez E, 2017) Phalimide ring

Figure 1
Figure 1 Mechanism of Action of Thalidomide

Table 1
Comparision of Pthalimide and Glutarimide Ring