102589-30-0Relevant articles and documents
Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents
Donkor, Isaac O.,Abdel-Ghany, Yasar S.,Kador, Peter F.,Mizoguchi, Tadashi,Bartoszko-Malik, Anita,Miller, Duane D.
, p. 235 - 243 (1999)
Derivatives of alrestatin (1-5) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase.
Alkylating Prazosin Analogue: Irreversible Label for α1-Adrenoceptors
Pitha, Josef,Szabo, Lajos,Szurmai, Zoltan,Buchowiecki, Wieslaw,Kusiak, John W.
, p. 96 - 100 (2007/10/02)
A series of prazosin analogues comprised of N-acyl derivatives of N'-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazine was prepared and the nature of their binding to α1-adrenoceptors was investigated.Derivatives with α,β-unsaturated acyclic acyls had some affinity but no irreversible action at the receptor.Other potent compounds, also without irreversible activity, contained cinnamoyl or (phenylamino)thiocarbonyl residues.High affinity and irreversible binding were obtained with a bicycloocta-2,5-dien-2-ylcarbonyl derivative.The conjugated double bond in this compound was in about the same position and distance from the pharmacophore as in some of the above compounds of high affinity but with no irreversible action.Two consecutive recognition steps were thought to be involved in irreversible blockade: reversible binding of the pharmacophore part of the molecule to the binding site of the receptor, followed by reaction of the chemoreactive part with an adjacent nucleophile of the receptor.The present results suggest that for the second step to occur efficiently, some affinity for the receptor must be present even in the chemoreactive part of the molecule; simple spanning of the binding and nucleophile sites of the receptor was insufficient.
