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Titolo:
NONPEPTIDE SOMATOSTATIN AGONISTS WITH SST(4) SELECTIVITY - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF THIOUREAS
Autore:
LIU SQ; TANG C; HO B; ANKERSEN M; STIDSEN CE; CRIDER AM;
Indirizzi:
NE LOUISIANA UNIV,SCH PHARM,DIV BASIC PHARMACEUT SCI MONROE LA 71209 NE LOUISIANA UNIV,SCH PHARM,DIV BASIC PHARMACEUT SCI MONROE LA 71209 NOVO NORDISK AS,MEDCHEM RES & MOL PHARMACOL DK-2760 MALOV DENMARK
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 24, volume: 41, anno: 1998,
pagine: 4693 - 4705
SICI:
0022-2623(1998)41:24<4693:NSAWSS>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-D-GLUCOSE; PHARMACOLOGICAL CHARACTERIZATION; GROWTH-HORMONE; RECEPTORS; DESIGN; POTENT; PEPTIDOMIMETICS; LOCALIZATION; ANTAGONISTS; ANALOGS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
S.Q. Liu et al., "NONPEPTIDE SOMATOSTATIN AGONISTS WITH SST(4) SELECTIVITY - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF THIOUREAS", Journal of medicinal chemistry, 41(24), 1998, pp. 4693-4705

Abstract

Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst(2) and sst(4) receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp(8) residue, (2) a nonheteroaromatic nucleus to mimic Phe(7), and (3) a primary amine or other basic group to mimic the Lys(9) residue of somatostatin. Displacement studies were carried out using membranes from cell lines expressing ssts [BHK cells (sst(4)) and HEK 293 cells (sst(2))] utilizing [I-125]Tyr(11)-SRIF as the radioligand. Several thioureas (11, 38, 39, 41, and 42) and the urea 66 exhibited K-i values of less than 100 nM. The thioureas 11 (K-i = 6 nM) and 41 (K-i = 16 nM) and the urea 66 (K-i = 14 nM) are believed to be the most potent nonpeptide sst(4) agonists known. Since the thiourea 11 and the urea 66 exhibit high ssts selectivity, these novel nonpeptide derivatives may be usefultools for studying the sst(4) receptor. Studies are currently in progress to evaluate the therapeutic potential of NNC 26-9100 (11) in the treatment of glaucoma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 22:40:22