Small molecule somatostatin receptor subtype-2 antagonists

被引：11

作者：

Hay, BA ^{[1
]}

Cole, BM ^{[1
]}

DiCapua, F ^{[1
]}

Kirk, GW ^{[1
]}

Murray, MC ^{[1
]}

Nardone, RA ^{[1
]}

Pelletier, DJ ^{[1
]}

Ricketts, AP ^{[1
]}

Robertson, AS ^{[1
]}

Siegel, TW ^{[1
]}

机构：

[1] Pfizer Inc, Groton Labs, Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(01)00568-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The first potent small molecule sst2 antagonists are reported. Altering known sst2 agonist molecules yielded compounds with high sst2 binding affinity and full antagonist activity. Compound 7a, for example, displaced somatostatin binding to the sst2 receptor with an IC50 = 2.9 nM and antagonized somatostatin action with an IC50 = 29 nM. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：2731 / 2734

页数：4

共 22 条

[1]

Bass RT, 1996, MOL PHARMACOL, V50, P709

[2] A linear hexapeptide somatostatin antagonist blocks somatostatin activity in vitro and influences growth hormone release in rats [J].

Baumbach, WR ;

Carrick, TA ;

Pausch, MH ;

Bingham, B ;

Carmignac, D ;

Robinson, ICAF ;

Houghten, R ;

Eppler, CM ;

Price, LA ;

Zysk, JR .

MOLECULAR PHARMACOLOGY, 1998, 54 (05) :864-873

[3] HYPOTHALAMIC POLYPEPTIDE THAT INHIBITS SECRETION OF IMMUNOREACTIVE PITUITARY GROWTH-HORMONE [J].

BRAZEAU, P ;

VALE, W ;

BURGUS, R ;

LING, N ;

BUTCHER, M ;

RIVIER, J ;

GUILLEMIN, R .

SCIENCE, 1973, 179 (4068) :77-79

[4] MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF A BRAIN-SPECIFIC SOMATOSTATIN RECEPTOR [J].

BRUNO, JF ;

XU, Y ;

SONG, JF ;

BERELOWITZ, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (23) :11151-11155

[5] SOMATOSTATIN INHIBITS VASOACTIVE INTESTINAL PEPTIDE-STIMULATED CYCLIC ADENOSINE-MONOPHOSPHATE ACCUMULATION IN GH PITUITARY-CELLS [J].

DORFLINGER, LJ ;

SCHONBRUNN, A .

ENDOCRINOLOGY, 1983, 113 (05) :1541-1550

[6] INHIBITION BY SOMATOSTATIN OF GLUCAGON AND INSULIN RELEASE FROM PERFUSED RAT PANCREAS IN RESPONSE TO ARGININE, ISOPROTERENOL AND THEOPHYLLINE - EVIDENCE FOR A PREFERENTIAL EFFECT ON GLUCAGON-SECRETION [J].

GERICH, JE ;

LOVINGER, R ;

GRODSKY, GM .

ENDOCRINOLOGY, 1975, 96 (03) :749-754

[7] Potent antagonists of somatostatin: Synthesis and biology [J].

Hocart, SJ ;

Jain, R ;

Murphy, WA ;

Taylor, JE ;

Morgan, B ;

Coy, DH .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (07) :1146-1154

[8] Highly potent cyclic disulfide antagonists of somatostatin [J].

Hocart, SJ ;

Jain, R ;

Murphy, WA ;

Taylor, JE ;

Coy, DH .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (11) :1863-1871

[9] EFFECTS OF SOMATOSTATIN ON GASTROINTESTINAL PROPAGATION AND ABSORPTION OF ORAL GLUCOSE IN MAN [J].

JOHANSSON, C ;

WISEN, O ;

EFENDIC, S ;

UVNASWALLENSTEN, K .

DIGESTION, 1981, 22 (03) :126-137

[10] Somatostatin receptors in Neuro2A neuroblastoma cells: Operational characteristics [J].

Koenig, JA ;

Edwardson, JM ;

Humphrey, PPA .

BRITISH JOURNAL OF PHARMACOLOGY, 1997, 120 (01) :45-51

← 1 2 3 →