Molecular features of the prazosin molecule required for activation of Transport-P.

Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important.

[1]  J P Monk,et al.  Terazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in essential hypertension. , 1987, Drugs.

[2]  H. Hess,et al.  Synthesis and identification of the major metabolites of prazosin formed in dog and rat. , 1977, Journal of medicinal chemistry.

[3]  K. Catt,et al.  High‐affinity uptake of noradrenaline in postsynaptic neurones , 1993, British journal of pharmacology.

[4]  J. Knutson,et al.  Visual detection of transport‐P in peptidergic neurones , 1997, British journal of pharmacology.

[5]  J. H. Williams,et al.  Anticonvulsants. Benzyl 4-carbamyl-1-piperazinecarboxylate and related compounds , 1953 .

[6]  Binding and competitive inhibition of amine uptake at postsynaptic neurones (transport‐P) by tricyclic antidepressants , 1996, British journal of pharmacology.

[7]  W. Shen,et al.  Release of amines from acidified stores following accumulation by Transport‐P , 2001, British journal of pharmacology.

[8]  A. Scriabine,et al.  Antihypertensive 2-amino-4(3H)-quinazolinones. , 1968, Journal of medicinal chemistry.

[9]  I. W. Waters,et al.  2-(beta-Arylethylamino)- and 4-(beta-arylethylamino)quinazolines as phosphodiesterase inhibitors. , 1985, Journal of medicinal chemistry.

[10]  I. Kopin,et al.  Structural properties of phenylethylamine derivatives which inhibit transport‐P in peptidergic neurones , 1998, British journal of pharmacology.

[11]  B. Lewis,et al.  2,4-diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1-yl] derivatives as alpha 1-adrenoceptor antagonists and antihypertensive agents. , 1987, Journal of medicinal chemistry.

[12]  Daqian Xu,et al.  Ethyl trifluoroacetate: a powerful reagent for differentiating amino groups , 1995 .

[13]  M. Cava,et al.  An Improved Synthesis of dl-Anonaine , 1966 .

[14]  I. Kopin,et al.  Functional properties of the uptake of amines in immortalised peptidergic neurones (transport‐P) , 1996, British journal of pharmacology.

[15]  C. Ganellin,et al.  Search for the pharmacophore in prazosin for Transport-P. , 2005, Bioorganic & medicinal chemistry.

[16]  W. Shen,et al.  α1B adrenergic receptors in gonadotrophin‐releasing hormone neurones: relation to Transport‐P , 2001, British journal of pharmacology.