Anticonvulsant activity of caramiphen analogs

DeHaven‐Hudkins, Diane L.; Allen, Josh; Hudkins, Robert L.; Stubbins, James F.; Tortella, Frank C.

doi:10.1016/0024-3205(95)00123-n

Cited by 7 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rossi et al reviewed the limited number of such ring closures in the context of S RN 1 reactions in general. 10 Many bioactive molecules, such as the anticonvulsant benzocaramiphen, 11 contain an Indane, tetralin, or analogous heterocyclic ring, embodying a quaternary center. The radical carbanion cyclo-coupling strategy appeared promising as a synthetic approach to such structures.…”

Section: Introductionmentioning

confidence: 99%

Effect of Chain Length on Radical to Carbanion Cyclo-Coupling of Bromoaryl Alkyl-Linked Oxazolines: 1,3-Areneotropic Migration of Oxazolines

et al. 2007

View full text Add to dashboard Cite

2-Halophenylalkyl-2-oxazolines with alkyl chain spacers of two to six C atoms (n = 0-4) were prepared and their SRN1-type reactions with several base systems examined. The best conditions to promote cyclo-coupling to the corresponding benzocycloalkane derivatives involved use of LDA in THF. The precursors with 3-C-atom and 4-C-atom spacers gave good yields of 2-(1'-phenylindan-1'-yl)-2-oxazolines and 2-(1-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)-2-oxazoline, respectively. The major products from the precursor with a 5-C-atom spacer were derivatives of benzocycloheptane in which the oxazoline group had undergone a novel areneotropic migration from the end of the spacer to the benzo ring. The product from reaction of the corresponding 2-C-atom precursor was a 9-oxazolinophenanthrene derivative. EPR spectroscopy showed the intermediates of the LDA-promoted reactions to be radical anions of the product benzocycloalkanes. This supported an SRN1-type chain mechanism involving initial production of aryl radicals connected to azaenolate ions via the spacer groups. Intramolecular radical to carbanion coupling then generated ring-closed benzocycloalkane radical anions that transferred an electron to more precursor. Diastereoselective radical to carbanion cyclo-coupling reactions were carried out with 2-bromophenylpropyl precursors containing chiral 2-oxazolines. The diastereoselectivity achievable was modest, but the product diastereoisomeric Indane derivatives were easily separable by chromatography.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of Chain Length on Radical to Carbanion Cyclo-Coupling of Bromoaryl Alkyl-Linked Oxazolines: 1,3-Areneotropic Migration of Oxazolines

et al. 2007

View full text Add to dashboard Cite

show abstract

“…[4][5][6] Anticonvulsant activity has been reported for the benzocaramiphen analogue 1. 7 Other aryl-substuted indan derivatives are also precursors for pharmaceuticals. 8 Our initial aim was to develop a new radical-carbanion coupling route to compounds of type 1 containing quaternary C-atoms.…”

mentioning

confidence: 99%

Radical-carbanion cyclo-coupling in armed aromatics: overriding steric hindrance to ring closure

Roydhouse

Walton

2005

Chem. Commun.

View full text Add to dashboard Cite

show abstract

“…In the present study lidocaine has a stronger frequency-dependent block of Na þ currents, whereas caramiphen displays a much weaker frequency-dependence of block. Caramiphen anticonvulsant activity has been hypothesized to be due to high-affinity binding to sigma recognition sites in brain (DeHaven-Hudkins et al, 1995). Hanner et al (Hanner et al, 1996) previously stated that the sigma-1 receptor is widely located within the rat central nervous system, particularly neuronal cell bodies and dendrites of brain stem, hypothalamus, and hippocampus, but not axon fibers or terminals, while the sigma-1 receptor on the other hand is known to be a facilitator of nociception.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, lidocaine is generally safer than racemic bupivacaine, because the sign of acute poisoning is noticed before cardiac arrest. Caramiphen has been shown to have an anticonvulsant effect (DeHaven-Hudkins et al, 1995), and therefore may have the effect on local anestheticsinduced neurological symptoms, such as convulsion. Our previous experiment showed that, at equipotent doses, the times required to cause seizure, respiratory arrest, and impending death were longer in the caramiphen group than in the bupivacaine group (Hung et al, 2012).…”

Section: Discussionmentioning

confidence: 99%