Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants

Malik, Shabnam; Ahuja, Priya; Sahu, Kapendra; Khan, Shahrukh Rafi

doi:10.1016/j.ejmech.2014.07.016

Cited by 35 publications

(8 citation statements)

References 35 publications

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“…However, only about 70% of patients suffering from epilepsy are adequately controlled by the currently available anti-epileptic drugs (AEDs) [5]. Therefore, the search for more effective and safer new AEDs should have a considerable attention.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of (2E)-2-[1-(4-bromophenyl)-3-(1H-imidazol-1-yl) propylidene]-N-(2,4-dichlorophenyl)hydrazinecarboxamide, C19H16BrCl2N5O

Al-Wabli

Attia

Ghabbour

et al. 2015

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of material(2.79 g, 10 mmol) and few drops of glacial acetic acid in ethanol (15 mL) was stirred at ambient temperature for 18 h. The reaction mixture was evaporated under reduced pressure and the residue was crystallized from ethanol to give 2.84 g (59%) of the title compound as colourless crystals which were suitable for single crystal x-ray analysis. m.p. 494-496 K. DiscussionEpilepsy is one of the most common disorders of the brain, affecting more than 50 million individuals worldwide [4]. However, only about 70% of patients suffering from epilepsy are adequately controlled by the currently available anti-epileptic drugs (AEDs) [5]. Therefore, the search for more effective and safer new AEDs should have a considerable attention. The title compound showed 16 and 50% seizure inhibition in animal model mice using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) convulsive screens, respectively, at a dose level of 520 mmol/kg [6]. X-ray crystallography is a decisive analytical tool which can confirm the configuration of the title compound. Fortunately, we have succeeded to get single crystals of the title compound which were suitable for x-ray crystallography. The crystal structure of the target compound contains one molecule in the asymmetric unit. The two six-membered rings (C1-C6 and C14-C19) are nearly planner. The dihedral angle between the two six-membered rings is 8.7(10)°. The dihedral angles between the six-membered rings (C1-C6 and C14-C19) and the imidazole ring (N1/N2/C10-C12) are 44.62(13)°and 48.82(13)°, respectively. The packing in the crystal structure is stabilized by two inter-molecular hydrogen bonds, of which N1 works as hydrogen bond acceptor and N4 and C4 work as hydrogen bond donors. The distance of the interactions between N46-H1N4×××N1 is 2.12(6) Å and C8-H8A×××N1 is 2.53(1) Å and the angles are 165.00(6)°and 141.00(1)°, respectively.

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Section: Discussionmentioning

confidence: 99%

Crystal structure of (2E)-2-[1-(4-bromophenyl)-3-(1H-imidazol-1-yl) propylidene]-N-(2,4-dichlorophenyl)hydrazinecarboxamide, C19H16BrCl2N5O

Al-Wabli

Attia

Ghabbour

et al. 2015

Zeitschrift Für Kristallographie - New Crystal Structures

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“…Figure 3). These compounds were more active and had lower neurotoxicity than the control drugs ethosuximide and phenytoin [61]. Figure 3).…”

Section: The Oxadiazole or Benzoxazinone Functional Groupsmentioning

confidence: 99%

Current Research on Antiepileptic Compounds

2015

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Epilepsy affects about 1% of the world's population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development of more effective and safer AEDs. Based on our research work on antiepileptic compounds and other references in recent years, this review covers the reported work on antiepileptic compounds which are classified according to their structures. This review summarized 244 significant anticonvulsant compounds which are classified by functional groups according to the animal model data, although there are some limitations in the data. This review highlights the properties of new compounds endowed with promising antiepileptic properties, which may be proven to be more effective and selective, and possibly free of unwanted side effects. The reviewed compounds represent an interesting possibility to overcome refractory seizures and to reduce the percentage of patients with a poor response to drug therapy.

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“…[109] The latter, of similar magnitude, has also been found in C3 phthalimide-substitutedb enzisoxazoles 37 ( Figure 12). [110] It is known that the functions of the CNS are controlled by l-glutamic acid (Glu) and g-aminobutyric acid (GABA), through their multiple receptors ubtypes. [110] It is known that the functions of the CNS are controlled by l-glutamic acid (Glu) and g-aminobutyric acid (GABA), through their multiple receptors ubtypes.…”

Section: Psychoactive Drugs (Psychotropics)mentioning

confidence: 99%

“…These drug leads have also been found to be more potent and less neurotoxic than their reference anti-epileptics phenytoin and ethosuximide. [110] It is known that the functions of the CNS are controlled by l-glutamic acid (Glu) and g-aminobutyric acid (GABA), through their multiple receptors ubtypes. Ligands with selectivea ffinity for theser eceptors have therapeutic potential for www.chemmedchem.org treating various neurological and mental disorders.I onotropic and metabotropic glutamate GABA and AMPAr eceptors (ligand-gated ion channels) are important for neurotransmission.…”

Section: Psychoactive Drugs (Psychotropics)mentioning

confidence: 99%

The Isoxazole Ring and Its N‐Oxide: A Privileged Core Structure in Neuropsychiatric Therapeutics

et al. 2017

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Mental disorders are neuropsychiatric conditions that are marked by unusual or irregular thinking, feelings, or behavior, and lead to distress and/or impaired functions. Major psychiatric conditions are depression, anxiety, and psychoses of various types. Their etiopathogeneses, of a primary or secondary origin, are associated with genetic and environmental factors. They are commonly treated with psychoactive drugs (also known as psychotropics), which target serotonin, dopamine, norepinephrine, glutamate, and nuclear receptors (NRs), including retinoic acid receptor-related orphan receptors (RORs) and other receptors in the central nervous system (CNS). Herein we present a diverse array of isoxazole derivatives, among which are some prominent marketed drugs. Some of the derivatives and forms, including N-oxides, are under either (pre)clinical evaluation or patent protection as new generation of psychotropics, and a few have effective blood-brain barrier (BBB) permeability. Various drug-like isoxazol(in)es and their structural features and efficiency, modified through scaffold hopping, are described and discussed in the context of treating neuropsychiatric conditions.

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Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants

Cited by 35 publications

References 35 publications

Crystal structure of (2E)-2-[1-(4-bromophenyl)-3-(1H-imidazol-1-yl) propylidene]-N-(2,4-dichlorophenyl)hydrazinecarboxamide, C19H16BrCl2N5O

Crystal structure of (2E)-2-[1-(4-bromophenyl)-3-(1H-imidazol-1-yl) propylidene]-N-(2,4-dichlorophenyl)hydrazinecarboxamide, C19H16BrCl2N5O

Current Research on Antiepileptic Compounds

The Isoxazole Ring and Its N‐Oxide: A Privileged Core Structure in Neuropsychiatric Therapeutics

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