Receptor barbiturates

Barbiturate receptors, derived from crown ethers, 24 47 Barbiturates, 10 529... 

Few examples of covalent and non-covalent DCLs have been reported over the past few years, with only a small number of them making use of hydrogen-bonding templates. One of such examples is the barbiturate receptor 73 reported by... 

Scheme 38 The formation of barbiturate receptor 73 is amplified in the presence of a barbiturate template... 

Barbiturate Amobarbital Amytal Barbiturate receptor (GABAA)... 

G. A. R. Johnson, M. Willow (1982). GABA and barbiturate receptors. In J. W. Lamble (Ed.). More About Receptors. Amsterdam Elsevier Biochemical Press. 

Often designated briefly as Hamilton receptor , this barbiturate receptor niche (Fig. 6.12) consists of an isophthaloyl spacer flanked by two acylated 2,6-diaminopyridine moieties. Macrocyclisation with a rigid diphenylmethane unit generates a non-collapsing host cavity suitable for selective complexation of barbiturate guest molecules via formation of six hydrogen bonds. 

This proven host system was transferred to dendrimers by functionalising the periphery of POPAM dendrimers with the acyclic Hamilton variant (Fig. 6.13). After monofunctionalisation with an amino group on the isophthaloyl system, it could be multiply covalently bonded to the dendrimer. In this way, up to fourth-generation POPAM dendrimers could be peripherally embellished with barbiturate receptors. The mode of action of the individual dendrimers as multivalent... 

The pioneering work in this area was reported by Lehn [80-83], both referring to ligand (imines) and to receptor libraries (barbiturate receptors and... 

Berl V, Hue I, Lehn JM, DeCian A, Fischer J, Induced fit selection of a barbiturate receptor from a dynamic structural and conformational/ configurational library, Eur. J. Org. Chem., 3089-3094, 1999. 

GABA. Dihydrovaltrate, hydroxyvalerenic acid, a hydroalcoholic extract containing 0.8% valerenic acid a lipid extract an aqueous extract of the hydroalcoholic extract, and another aqueous extract of V. officinalis (L.) were assessed for in vitro binding to rat GABA, benzodiazepine, and barbiturate receptors (18). The results indicated that an interaction of some component of the hydroalcoholic extract, the aqueous extract derived from the hydroalcoholic extract, and the other aqueous extract had affinity for the GABAa receptor. Because hydroxyvalerenic acid (a volatile oil sesquiterpene) and dihydrovaltrate (a valepotriate) did not show any notable activity, the investigators could not identify the specific constituents responsible for this activity. The lipophilic extract derived from the hydroalcoholic extract, as well as dihydrovaltrate, showed affinity for barbiturate receptors, and some affinity for peripheral benzodiazepine receptors. 

Mennini P, Bemasconi P, Bombardelli E, Morazzoni P. In vitro study on the interaction of extracts and pure compounds from Valeriana officinalis roots with GABA, benzo-diazepine and barbiturate receptors in rat brain. Fitoterapia 1993 64 291-300. 

Barbiturates bind to barbiturate receptors on the chloride channel (see Figure, question 5). Activation of the receptor potentiates the effects of GABA, and increases chloride flux across the neuronal membrane, causing partial hyperpolarization of the neuronal membrane, and decreased conduction. Because the barbiturate receptor is adjacent to both the benzodiazepine receptor and GABA receptor on the channel, the action of barbiturates enhances not only the binding of GABA to its receptor, but the receptor binding of benzodiazepines as well. 

Figure 3.6. Schematic model of the GABA/Benzodiaz-epine/Barbiturate receptor complex. The receptor complex surrounds a chloride ion channel. Camma-amin o butyric acid (GABA) is an inhibitory neurotransmitter. GABA binds to the receptor causing chloride influx. The movement of chloride into the neuron hyperpolarizes the neuronal membrane, making it more difficult for excitatory neurotransmitters to depolarize the cell. Benzodiazepines and barbiturates enhance the actions of GABA, but fail to open the chloride channel in the absence of GABA.

A. All barbiturates cause generalized depression of neuronal activity in the brain. Interaction with a barbiturate receptor leads to enhanced gamma-aminobutyric acid (GABA)-mediated chloride currents and results in synaptic inhibition. Hypotension that occurs with large doses is caused by depression of central sympathetic tone as well as by direct depression of cardiac contractility. 

Figure 1 Hamilton s barbiturate receptor 1 in equilibrium with its target guest diethyl barbital 2.

One of the simplest ways to make rotaxanes has been recently introduced by Vogtle. It involves the alkylation of a phen-oxide or alkoxide anion with an alkyl halide. By examining the barbiturate receptor of Figure 4.8 A, write down a reaction sec ucnce that could create a rotaxane. 

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