17β-Nitro-5α-androstan-3α-ol and its 3β-methyl derivative: Neurosteroid analogs with potent anticonvulsant and anxiolytic activities

Runyon, Scott P.; Orr, Matthew D.; Navarro, Hernán A.; Kepler, John A.; Rogawski, Michael A.; Kamiński, Rafał M.; Cook, Clarence

doi:10.1016/j.ejphar.2009.06.052

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…When the results were compared with pregnanolone 5α-Pregnan-3β-ol-20-one (allopregnanolone), compounds 75 and 76 displayed similar potency as that of allopregnanolone in the PTZ model whereas, in the 6 Hz the compounds appeared to be more potent. The compounds 75 and 76 possessed ED 50 = 12.9 (9.8-16.9), 10 (8.9-11.2) and 5.3 (4.6-6.1), 8.8 (7.1-10.8) mg/kg in PTZ and 6 Hz model, respectively [ 87 ]. The finding of the study shows that in the compounds, the nitro group at the 17 th position works as bioisosteres to the acetyl group present in the allopregnanolone.…”

Section: Synthetic Pathway Of Non-nitrogen Heterocyclic Compounds As ...mentioning

confidence: 99%

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents

Pal¹,

Singh²,

Paul³

et al. 2022

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: Epilepsy is a chronic neurological disorder, characterized by predisposition of unprovoked seizures affecting the neurobiological, psychological, cognitive, economic, and social well-being of patient. As per the 2019 report by World Health Organization, it affects nearly 80% of the population which comes from the middle to low-income countries. It has been suggested that 70% of such cases can be treated effectively if properly diagnosed. It is one of the most common neurological diseases affecting 50 million people globally. Most of the antiepileptic drugs used in clinical practice are only 60-80% effective in controlling the disease. These drugs suffer from serious drawbacks of non-selectivity and toxicity that limit their clinical usefulness. Hence, there is a need to search for the safe, potent, and effective anti-epileptic drugs. One of the emerging strategies to discover and develop selective and non-toxic anticonvulsant molecule focuses on design of non-nitrogen heterocyclic compounds (NNHC). Drugs such as valproic acid, gabapentin, viagabatrin, fluorofelbamate, tiagabine, progabide, pregabalin, gamma amino butyric acid (GABA) etc., do not contain a nitrogen heterocyclic ring but are as effective anticonvulsants as conventional heterocyclic nitrogen compounds. This review covers the various classes of NNHC which have been developed in the recent past as anticonvulsants along with their chemistry, percentage yield, structure activity relationship and biological activity. The most potent compound in each series has been identified for the comparative studies, for further structural modification and to improve the pharmacokinetic profile. Various optimized synthetic pathways and diverse functionalities other than nitrogen-containing rings discussed in the article may help medicinal chemists to design safe and effective anticonvulsant drugs in near future.

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Section: Synthetic Pathway Of Non-nitrogen Heterocyclic Compounds As ...mentioning

confidence: 99%

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents

Pal¹,

Singh²,

Paul³

et al. 2022

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“…Acute ethanol and/or stress increases central neurosteroid levels and enhances GABA-A receptor activity [314, 370, 374]. A number of patents for treating alcoholism that involve the androstane category of neurosteroids have been granted [375, 376] including dehydroepiandrosterone [DHEA: 377]. Substantial research indicates that the brain synthesizes estrogen [373].…”

Section: Other Neurobiological Systems Mediating the Development And mentioning

confidence: 99%

Introduction to the Special Issue “Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence” and a Summary of Patents Targeting other Neurotransmitter Systems

Bell

Franklin²,

Hauser³

et al. 2012

RPCN

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This paper introduces the Special Section: Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence and provides a summary of patents targeting neurotransmitter systems not covered in the other four chapters. The World Health Organization notes that alcoholic-type drinking results in 2.5 million deaths per year, and these deaths occur to a disproportionately greater extent among adolescents and young adults. Developing a pharmacological treatment targeting alcohol abuse and dependence is complicated by (a) the heterogeneous nature of the disease(s), (b) alcohol affecting multiple neurotransmitter and neuromodulator systems, and (c) alcohol affecting multiple organ systems which in turn influence the function of the central nervous system. Presently, the USA Federal Drug Administration has approved three pharmacotherapies for alcoholism: disulfiram, naltrexone, and acamprosate. This chapter provides a summary of the following systems, which are not covered in the accompanying chapters; alcohol and acetaldehyde metabolism, opioid, glycinergic, GABA-A, neurosteroid, dopaminergic, serotonergic, and endocannabinoid, as well as patents targeting these systems for the treatment of alcoholism. Finally, an overview is presented on the use of pharmacogenetics and pharmacogenomics in tailoring treatments for certain subpopulations of alcoholics, which is expected to continue in the future.

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Organocatalytic Asymmetric Cascade Reactions Based on Gamma‐Nitro Carbonyl Compound

Guo

Peng

et al. 2018

The Chemical Record

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The significant advancements in asymmetric organocascade reactions have been accomplished during the past decades, paving the way to the efficient and stereoselective construction of structurally complex scaffolds from simple and readily available starting materials. Nitro-containing cyclic compounds have become a privileged molecular library given their broad and promising activities in various therapeutic areas. In various approaches to build these valuable scaffolds, the utility of γ-nitrocarbonyl intermediates is one of the most efficient approaches due to its high efficiency, reliability and versatility. The strategies and catalyst systems described here highlight recent advances in the enantioselective synthesis of nitro-containing cyclic molecules via organocascade strategies based on γ-nitrocarbonyl intermediates. Various organocatalysts with distinct activation modes have found application in providing these sophisticated compounds. This review is organized according to the types of organocatalyst. These methods are of importance for the construction of complex chiral cyclic frameworks and the design of new pharmaceutical compounds. We believe that compounds based on nitro-containing cyclic skeletons have the potential to provide novel therapeutic agents and useful biological tools.

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17β-Nitro-5α-androstan-3α-ol and its 3β-methyl derivative: Neurosteroid analogs with potent anticonvulsant and anxiolytic activities

Cited by 6 publications

References 21 publications

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents

Introduction to the Special Issue “Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence” and a Summary of Patents Targeting other Neurotransmitter Systems

Organocatalytic Asymmetric Cascade Reactions Based on Gamma‐Nitro Carbonyl Compound

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