Synthesis and biological activity of fluoro-substituted pyrrolo[2,3-d]pyrimidines:: The development of potential positron emission tomography imaging agents for the corticotropin-releasing hormone type 1 receptor

被引：21

作者：

Hsin, LW

Webster, EL

Chrousos, GP

Gold, PW

Eckelman, WC

Contoreggi, C

Rice, KC ^{[1
]}

机构：

[1] NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA

[2] NIMH, Clin Neuroendocrinol Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA

[3] NICHD, Pediat Endocrinol Sect, PREB, Clin Ctr,NIH, Bethesda, MD 20892 USA

[4] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA

[5] NIDA, Brain Imaging Unit, Baltimore, MD 21224 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(00)00071-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of fluoro-substituted 4-(dialkylamino)pyrrolo[2,3-n]pyrimidines was synthesized and their binding affinity for corticotropin-releasing hormone type 1 receptor (CRHR1) was investigated. Compounds 11a and 11b possessed very high CRHR1 affinity (K-i = 3.5, 0.91 nM, respectively). They are promising candidates for the development of F-18-containing nonpeptide PLT radioligands for CRHR1. Published by Elsevier Science Ltd.

引用

页码：707 / 710

页数：4

共 19 条

[1] Non-peptide corticotropin-releasing hormone antagonists: Syntheses and structure-activity relationships of 2-anilinopyrimidines and -triazines [J].

Arvanitis, AG ;

Gilligan, PJ ;

Chorvat, RJ ;

Cheeseman, RS ;

Christos, TE ;

Bakthavatchalam, R ;

Beck, JP ;

Cocuzza, AJ ;

Hobbs, FW ;

Wilde, RG ;

Arnold, C ;

Chidester, D ;

Curry, M ;

He, LQ ;

Hollis, A ;

Klaczkiewicz, J ;

Krenitsky, PJ ;

Rescinito, JP ;

Scholfield, E ;

Culp, S ;

De Souza, EB ;

Fitzgerald, L ;

Grigoriadis, D ;

Tam, SW ;

Wong, YN ;

Huang, SM ;

Shen, HL .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (05) :805-818

[2] The CRF1 receptor mediates the excitatory actions of corticotropin releasing factor (CRF) in the developing rat brain: in vivo evidence using a novel, selective, non-peptide CRF receptor antagonist [J].

Baram, TZ ;

Chalmers, DT ;

Chen, C ;

Koutsoukos, Y ;

DeSouza, EB .

BRAIN RESEARCH, 1997, 770 (1-2) :89-95

[3]

Bremner JD, 1997, AM J PSYCHIAT, V154, P624

[4]

Chen C, 1996, J MED CHEM, V39, P4358

[5] Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: A centrally active corticotropin-releasing factor(1) receptor antagonist [J].

Chen, YL ;

Mansbach, RS ;

Winter, SM ;

Brooks, E ;

Collins, J ;

Corman, ML ;

Dunaiskis, AR ;

Faraci, WS ;

Gallaschun, RJ ;

Schmidt, A ;

Schulz, DW .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (11) :1749-1754

[6]

CHEN YL, Patent No. 9413676

[7] Synthesis, corticotropin-releasing factor receptor binding affinity, and pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and -pyridines [J].

Chorvat, RJ ;

Bakthavatchalam, R ;

Beck, JP ;

Gilligan, PJ ;

Wilde, RG ;

Cocuzza, AJ ;

Hobbs, FW ;

Cheeseman, RS ;

Curry, M ;

Rescinito, JP ;

Krenitsky, P ;

Chidester, D ;

Yarem, JA ;

Klaczkiewicz, JD ;

Hodge, CN ;

Aldrich, PE ;

Wasserman, ZR ;

Fernandez, CH ;

Zaczek, R ;

Fitzgerald, LW ;

Huang, SM ;

Shen, HL ;

Wong, YN ;

Chien, BM ;

Quon, CY ;

Arvanitis, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (05) :833-848

[8] SEMINARS IN MEDICINE OF THE BETH-ISRAEL-HOSPITAL, BOSTON - THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE-MEDIATED INFLAMMATION [J].

CHROUSOS, GP .

NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (20) :1351-1362

[9] The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress [J].

Deak, T ;

Nguyen, KT ;

Ehrlich, AL ;

Watkins, LR ;

Spencer, RL ;

Maier, SF ;

Licinio, J ;

Wong, ML ;

Chrousos, GP ;

Webster, E ;

Gold, PW .

ENDOCRINOLOGY, 1999, 140 (01) :79-86

[10]

Griebel G, 1998, PSYCHOPHARMACOLOGY, V138, P55

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