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Titolo:
Indole amide derivatives: synthesis, structure-activity relationships and molecular modelling studies of a new series of histamine H-1-receptor antagonists
Autore:
Battaglia, S; Boldrini, E; Da Settimo, F; Dondio, G; La Motta, C; Marini, AM; Primofiore, G;
Indirizzi:
Univ Pisa, Dipartimento Sci Farmaceut, I-56126 Pisa, Italy Univ Pisa Pisa Italy I-56126 rtimento Sci Farmaceut, I-56126 Pisa, Italy Farmigea SpA, I-56127 Pisa, Italy Farmigea SpA Pisa Italy I-56127Farmigea SpA, I-56127 Pisa, Italy SmithKline Beecham SpA, I-20021 Milan, Italy SmithKline Beecham SpA Milan Italy I-20021 ham SpA, I-20021 Milan, Italy
Titolo Testata:
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
fascicolo: 2, volume: 34, anno: 1999,
pagine: 93 - 105
SICI:
0223-5234(199902)34:2<93:IADSSR>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
N-HETEROCYCLIC 4-PIPERIDINAMINES; ANTIHISTAMINIC ACTIVITY; QUANTITATIVE STRUCTURE; BIOLOGICAL EVALUATION; RECEPTOR ANTAGONISTS; H-1-ANTAGONISTS; ANALOGS; AGENTS;
Keywords:
indole derivatives; non-classic H-1-antagonists; astemizole; structure-activity relationships;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Da Settimo, F Univ Pisa, Dipartimento Sci Farmaceut, Via Bonanno 6, I-56126 Pisa, Italy Univ Pisa Via Bonanno 6 Pisa Italy I-56126 6126 Pisa, Italy
Citazione:
S. Battaglia et al., "Indole amide derivatives: synthesis, structure-activity relationships and molecular modelling studies of a new series of histamine H-1-receptor antagonists", EUR J MED C, 34(2), 1999, pp. 93-105

Abstract

A number of indole amide derivatives bearing a basic side chain, in which the indole ring replaces the isoster benzimidazole nucleus typical of some well-known antihistamines, were prepared and tested for their H-1-antihistaminic activity. The 1-benzyl-3-indolecarboxamides 32-42 showed antihistaminic (H-1) activity (pA(2) 6-8); the 3-indolylglyoxylylamides 7-16 and the 2-indolecarboxamides 48-56 showed little or no activity. Insertion of the basic side chain of the active 3-indolecarboxamide derivatives into a piperazine ring (compounds 57-59) led to a dramatic loss of activity. All the active compounds proved to be competitive antagonists, since the values of the regression slope were not statistically different from 1. The most active compounds, 32, 33, 38-41, were also tested both in vitro for their anticholinergic activity and in vivo for their ability to antagonize histamine-induced cutaneous vascular permeability in rats. The biological results and the structure-activity relationships of the novel compounds are discussed in thelight of molecular modelling studies, taking the molecule of astemizole asa model, and referring to proposed H-1-receptor pharmacophore models. (C) Elsevier, Paris.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/06/18 alle ore 17:28:41