Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Advancement of <i>N</i>-((Benzo[<i>b</i>]thien-3-yl)methyl)sulfamide (JNJ-26990990) into Human Clinical Studies

Parker, Michael H.; Smith‐Swintosky, Virginia L.; McComsey, David F.; Huang, Yaoxin; Brenneman, Douglas E.; Klein, Brian D.; Malatyńska, Ewa; White, H. Steve; Milewski, Michael E.; Herb, Mark; Finley, Michael; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Iannucci, Robert; Leclercq, Laurent; Cuyckens, Filip; Reitz, Allen B.; Maryanoff, Bruce E.

doi:10.1021/jm801432r

Cited by 32 publications

(43 citation statements)

References 54 publications

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“…Although the sulphamide group was initially considered not particularly suitable for obtaining potent CAIs 22 , several compounds containing a primary sulphamide moiety have also been proved to possess a high CA inhibition activity 1,11,19,23 . As an example, compound JNJ-26990990 (2) (see Figure 1), which presents excellent anticonvulsant activity and can be potentially used in the treatment of multiple forms of epilepsy, is also a nanomolar inhibitor of several CA isoforms 24,25 . We recently reported the synthesis of a series of sulphonamide/sulphamide/sulphamate derivatives incorporating nitroimidazole moieties 26 .…”

Section: Introductionmentioning

confidence: 99%

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

Simone

Langella

Esposito

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

Simone

Langella

Esposito

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Another research group who studied on sulfamide group to design new anticonvulsant compounds by replacing sulfamate group with sulfamide isoster was Parker and coworkers [210]. They incorporated sulfamide moiety into different aryl groups such as benzothiophene, benzofurane, indole, naphthalene substituted with different halogen or methyl groups (65).…”

Section: Sulfamide Derivativesmentioning

confidence: 99%

Recent Progress in Anticonvulsant Drug Research: Strategies for Anticonvulsant Drug Development and Applications of Antiepileptic Drugs for Non-Epileptic Central Nervous System Disorders

Dalkara

Karakurt²

2012

CTMC

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Major advances in antiepileptic drug therapy have taken place since 1950s. In the first period, several antiepileptic drugs (AEDs) such as phenobarbital, diphenylhydantoin, ethosuximide, carbamazepine, benzodiazepines and valproic acid were introduced to epilepsy treatment. After 1990 many new generation drugs (lamotrigine, topiramate, gabapentine, pregabaline, felbamate, lacosamide, levetiracetam etc.) have been developed. These novel AEDs have offered some advantages such as fewer side effects, fewer drug-drug interactions, and better pharmacokinetic properties. But pharmacoresistance and therapeutic failure in 20-25% of the patients remain the main reasons to continue efforts to find safer and more efficacious drugs and ultimate a treatment for this devastating disease. Several AEDs especially novel compounds have been found to be effective also in the treatment of several other neurologic and psychiatric disorders. Chemical diversity of the newer antiepileptic drugs as well as those currently in clinical development is another point that encourages medicinal chemists to study this subject. This review summarizes recent studies on the development of potential anticonvulsant compounds in different chemical structures, their structure-activity relationships and also therapeutic usages of AEDs other than epilepsy.

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“…One analogue from these efforts, RWJ 37947, a cyclic sulfate analogue of topiramate, reportedly entered development, but no new information on this compound has appeared since 2002. A recent report on the design of additional topiramate analogues [92] indicates that the high potency of this compound against carbonic anhydrase enzymes was thought likely to lead to undesirable side effects in certain patients and prevented its further development.…”

Section: Topiramatementioning

confidence: 99%

“…Two recent patents and one publication disclose analogues, such as JNJ-26990990 (Figure 2.25), which bear some resemblance to the structural motifs in the original manuscript on topiramate [92][93][94]. A full report that details the optimization process leading to this clinical candidate has appeared.…”

Section: Topiramatementioning

confidence: 99%

Standalone Drugs

Proudfoot

2010

Analogue‐Based Drug Discovery II

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In volume I of Analogue-Based Drug Discovery we focused on analogue drugs with a double similarity, that is, those that are similar to another drug from both chemical and pharmacological viewpoints. These were referred to as structural and pharmacological analogues or, alternatively, full analogues. One special class of these analogues is considered to be direct analogues if they have identical pharmacophores -that is, they can be described by a general structure that includes most of the chemical skeleton. The book also discussed some examples of structural analogues, in which the similarity is limited to their chemical structures since they possess different pharmacological properties. We also proposed the term pharmacological analogues for drugs that have completely different chemical structures but similar pharmacological properties.Analogues are based on following a lead compound, and if this compound were a drug that opened up a new therapeutic treatment then we use the term pioneer drug. Such a drug is often referred to as first in class. One can subdivide pioneer drugs into those that have analogues and those that do not. Thus, the latter group provides a special subclass called standalone drugs,

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Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Advancement of N-((Benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into Human Clinical Studies

Cited by 32 publications

References 54 publications

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

Recent Progress in Anticonvulsant Drug Research: Strategies for Anticonvulsant Drug Development and Applications of Antiepileptic Drugs for Non-Epileptic Central Nervous System Disorders

Standalone Drugs

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