Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
SYNTHESIS AND ANTI-HIV-1 ACTIVITY OF A SERIES OF IMIDAZO[1,5-B]PYRIDAZINES
Autore:
LIVERMORE DGH; BETHELL RC; CAMMACK N; HANCOCK AP; HANN MM; GREEN DVS; LAMONT RB; NOBLE SA; ORR DC; PAYNE JJ; RAMSAY MVJ; SHINGLER AH; SMITH C; STORER R; WILLIAMSON C; WILLSON T;
Indirizzi:
GLAXO GRP RES LTD,DEPT MED CHEM 2,GREENFORD RD GREENFORD MIDDX ENGLAND GLAXO GRP RES LTD,DEPT VIROL GREENFORD MIDDX ENGLAND GLAXO GRP RES LTD,COMPUTAT CHEM GRP GREENFORD MIDDX ENGLAND
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 24, volume: 36, anno: 1993,
pagine: 3784 - 3794
SICI:
0022-2623(1993)36:24<3784:SAAAOA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; NONNUCLEOSIDE INHIBITORS; CRYSTAL-STRUCTURE; DERIVATIVES; REPLICATION; INVITRO; POTENT; AIDS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
D.G.H. Livermore et al., "SYNTHESIS AND ANTI-HIV-1 ACTIVITY OF A SERIES OF IMIDAZO[1,5-B]PYRIDAZINES", Journal of medicinal chemistry, 36(24), 1993, pp. 3784-3794

Abstract

A series of substituted imidazo[1,5-b]pyridazines have been prepared and tested for inhibitory activity against the reverse transcriptase of HIV-1 (RT) and their ability to inhibit the growth of infected MT-4 cells. Crystal data are reported on two compounds, 15c and 33. From the structure-activity relationships developed within this and other series, it is proposed that key features of the interaction with RT include hydrogen-bond acceptor and aromatic pi-orbital bonding with the imidazopyridazine nucleus and a benzoyl function separated from the heterocycle by a suitable spacer group. Exceptional activity against the reverse transcriptase of HIV-1 (IC50 = 0.65 nM) was obtained with a 2-imidazolyl-substituted derivative, midazo-[1,5-b]pyridazin-7-yl]-1-phenyl-1-heptanone (33) which is attributed to additional binding of the imidazole sp(2) nitrogen atom. A number of the compounds in this series also inhibit the replication of HIV-1 in vitro in MT-4 and C8166 cellsat levels observed with the nucleoside AZT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 07:01:29