Solid-Supported Synthesis and 5-HT7/5-HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5-dihydro-1,2,4-triazine-6-(1H)-one

被引：4

作者：

Grychowska, Katarzyna ^{[1
]}

Masurier, Nicolas ^{[2
]}

Verdie, Pascal ^{[2
]}

Satala, Grzegorz ^{[3
]}

Bojarski, Andrzej J. ^{[3
]}

Martinez, Jean ^{[2
]}

Pawlowski, Maciej ^{[1
]}

Subra, Gilles ^{[2
]}

Zajdel, Pawel ^{[1
]}

机构：

[1] Jagiellonian Univ, Dept Med Chem, Coll Med, PL-30688 Krakow, Poland

[2] Inst Biomol Max Mousseron, UMR CNRS 5247, Dept Aminoacids Peptides & Prot, F-34093 Montpellier, France

[3] Polish Acad Sci, Inst Pharmacol, Dept Med Chem, PL-31343 Krakow, Poland

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2015年 / 86卷 / 04期

关键词：

5-HT(1A)Rs ligands; 5-HT(7)Rs ligands; long-chain arylpiperazines; solid-phase synthesis; triazinones; CENTRAL-NERVOUS-SYSTEM; 5-HT7; RECEPTOR; PHASE SYNTHESIS;

D O I：

10.1111/cbdd.12539

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of arylpiperazinylbutyl derivatives of 4,5-dihydro-1,2,4-triazine-6(1H)-ones was designed and synthesized according to the new solid-supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc-protected glycine. The library representatives showed different levels of affinity for 5-HT7 and 5-HT1A receptors; compounds 13, 14 and 18-20 were classified as dual 5-HT7/5-HT1A receptors ligands. The structure-affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety.

引用

页码：697 / 703

页数：7

共 23 条

[1] Solid-phase synthesis of functionalized 1,2,4-triazin-6-ones [J].

Blass, BE ;

Coburn, KR ;

Faulkner, AL ;

Liu, S ;

Ogden, A ;

Portlock, DE ;

Srivastava, A .

TETRAHEDRON LETTERS, 2002, 43 (45) :8165-8167

[2] Efficient solid-phase synthesis of 4,5-dihydro-1,2,4-triazin-6(1H)-ones [J].

Boeglin, D ;

Cantel, S ;

Martinez, J ;

Fehrentz, JA .

TETRAHEDRON LETTERS, 2003, 44 (03) :459-462

[3]

BOJARSKI AJ, 1993, PHARMAZIE, V48, P289

[4]

Chan P., 1998, USA Patent, Patent No. [US 4743586, 4743586]

[5]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[6]

Freidinger RM., 1993, U.S. Patent, Patent No. [5,177,071, 5177071]

[7]

Handzlik J., 2004, EUR J MED CHEM, V6, P324

[8] The 5-HT7 receptor and disorders of the nervous system: an overview [J].

Hedlund, Peter B. .

PSYCHOPHARMACOLOGY, 2009, 206 (03) :345-354

[9] Tetrahydrobenzindoles:: Selective antagonists of the 5-HT7 receptor [J].

Kikuchi, C ;

Nagaso, H ;

Hiranuma, T ;

Koyama, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (04) :533-535

[10] The rise, fall and reinvention of combinatorial chemistry [J].

Kodadek, Thomas .

CHEMICAL COMMUNICATIONS, 2011, 47 (35) :9757-9763

← 1 2 3 →