Synthesis and pharmacological profile of new 1,3-disubstituted cyclohexanes as leukotriene B4 receptor antagonists

Poudrel, Jean-Marc; Hullot, Pierre; Vidal, Jean‐Pierre; Girard, Jean‐Pierre; Rossi, Jean‐Claude; Müller, Agnès; Bonne, C.

doi:10.1016/0960-894x(96)00424-6

Cited by 8 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many disubstituted cyclohexane derivatives have proven to elicit a broad‐spectrum of biological activities Among these are anticonvulsants such as Gabapentin andGabapentin enacarbil, and analgesics such as Tramadol, Ciramadol, Nerixidine and Phencyclidine (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Modeling, Anticonvulsant and Antinociceptive Properties of New 1,1‐Disubstituted Cyclohexane and 1,3‐Diazaspiro[4.5]decane Derivatives

et al. 2019

View full text Add to dashboard Cite

The current work describes the synthesis of new series of N-(1-(cyclohexylcarbamoyl) cyclohexyl)-N-phenylarylamides (10 a-h) and 3-cyclohexyl-1,2-diphenyl and 2-(substituted phenyl)-1,3diazaspiro[4.5]decanes (12 a-h).The new compounds were screened for their anticonvulsant and antinociceptive activities using sodium valproate and tramadol hydrochloride, respectively as reference standards. 4-Chloro-N-(1-(cyclohexylcarbamoyl)cyclohexyl)-N-phenylbenzamide (10 b), 3-Cyclohexyl-1,2diphenyl-1,3-diazaspiro[4.5]decane (12 a) and 3-Cyclohexyl-1phenyl-2-(3,4,5-trimethoxyphenyl)-1,3-diazaspiro[4.5]decane (12 d) showed higher anticonvulsant activity than sodium valproate at dose 0.08 mmol/kg. On the other hand, 4-Amino-N- (1-(cyclohexylcarbamoyl) cyclohexyl)-N-phenylbenzamide (10 h) and 3-Cyclohexyl-1-phenyl-2-(3,4,5-trimethoxyphenyl)-1,3-diazaspiro[4.5]decane (12 d) exhibited higher antinociceptive potential in both intensity and duration than tramadol hydrochloride. The pharmacokinetics of the new compounds were calculated in-silico. Additionally, 3D pharmacophoric model was generated.[a] Prof.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Modeling, Anticonvulsant and Antinociceptive Properties of New 1,1‐Disubstituted Cyclohexane and 1,3‐Diazaspiro[4.5]decane Derivatives

et al. 2019

View full text Add to dashboard Cite

show abstract

“…1,1‐Disubstituted cycloalkanes were reported to display a broad spectrum of biological activities among which the anticonvulsant one and the antiepileptic one such as gabapentin as depicted in Figure .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, molecular modeling studies, and anticonvulsant evaluation of novel 1‐((2‐hydroxyethyl)(aryl)amino)‐N‐substituted cycloalkanecarboxamides and their acetate esters

Aboul‐Enein

El‐Azzouny

Amin

et al. 2018

Archiv der Pharmazie

View full text Add to dashboard Cite

A series of 1-((2-hydroxyethyl)(aryl)amino)-N-substituted cycloalkanecarboxamides IXa-l and their acetate esters Xa-l were designed and synthesized as new anticovulsant agents. The evaluation of the anticonvulsant effect was performed in vivo by subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) tests in mice. Further, neurotoxicity, hepatotoxicity, and acute toxicity were determined. All the new candidates displayed 100% anticonvulsant activity in the scPTZ screen in the dose range of 0.0057-0.283 mmol/kg. The most potent compounds in the scPTZ screen were Xh (ED 50 = 0.0012 mmol/kg), Xd (ED 50 = 0.002 mmol/kg), Xf (ED 50 = 0.004 mmol/kg), IXj (ED 50 = 0.0047 mmol/kg), Xl (ED 50 = 0.0076 mmol/kg), and Xi (ED 50 = 0.008 mmol/kg). They exhibited higher fold activity in the anticonvulsant potential than the gold standards, phenobarbital and ethosuximide. Compound Xf was active in both scPTZ and MES screens. It showed ED 50 of 0.016 mmol/kg in MES screen. In the neurotoxicity screens, none of the test compounds displayed any minimal motor impairment at the maximum administered dose. The 3D pharmacophore model using Biova 1 Discovery Studio 2016 programs exhibited high fit value. The anticonvulsant evaluation results were compatible with the molecular modeling study. K E Y W O R D S 1-[(2-hydroxyethyl)(aryl)amino]-N-

show abstract

ChemInform Abstract: Synthesis and Pharmacological Profile of New 1,3‐Disubstituted Cyclohexanes as Leukotriene B4 Receptor Antagonists.

Poudrel¹,

Hullot²,

Vidal³

et al. 1997

ChemInform

View full text Add to dashboard Cite

Synthesis and Pharmacological Profile of New 1,3-Disubstituted Cyclohexanes as Leukotriene B4 Receptor Antagonists.-Novel non-aromatic members of stable leukotriene B4 antagonists such as (VIII) and (IX) are described, in which the conjugated double bond of the natural eicosanoid (X) is replaced by a 1,3-disubstituted cyclohexane ring.-(POUDREL, J. M.; HULLOT, P.; VIDAL, J. P.; GIRARD, J. P.; ROSSI, J. C.; MULLER, A.; BONNE, C.; Bioorg. Med.

show abstract

Synthesis and pharmacological profile of new 1,3-disubstituted cyclohexanes as leukotriene B4 receptor antagonists

Cited by 8 publications

References 24 publications

Synthesis, Molecular Modeling, Anticonvulsant and Antinociceptive Properties of New 1,1‐Disubstituted Cyclohexane and 1,3‐Diazaspiro[4.5]decane Derivatives

Synthesis, Molecular Modeling, Anticonvulsant and Antinociceptive Properties of New 1,1‐Disubstituted Cyclohexane and 1,3‐Diazaspiro[4.5]decane Derivatives

Synthesis, molecular modeling studies, and anticonvulsant evaluation of novel 1‐((2‐hydroxyethyl)(aryl)amino)‐N‐substituted cycloalkanecarboxamides and their acetate esters

ChemInform Abstract: Synthesis and Pharmacological Profile of New 1,3‐Disubstituted Cyclohexanes as Leukotriene B4 Receptor Antagonists.

Contact Info

Product

Resources

About