Parallel synthesis and biological screening of dopamine receptor ligands taking advantage of a click chemistry based BAL linker

被引:62
作者
Bettinetti, L [1 ]
Löber, S [1 ]
Hübner, H [1 ]
Gmeiner, P [1 ]
机构
[1] Univ Erlangen Nurnberg, Dept Med Chem, Emil Fischer Ctr, D-91052 Erlangen, Germany
来源
JOURNAL OF COMBINATORIAL CHEMISTRY | 2005年 / 7卷 / 02期
关键词
D O I
10.1021/cc049860s
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
The click-chemistry-derived formyl indolyl methyl triazole (FIMT) resin 1a was evaluated for the parallel solid-phase synthesis of a series of BP-897-type arylcarboxamides. By application of a five-step sequence (including loading by reductive amination, subsequent amide coupling, deprotection, palladium-catalyzed N-arylation, and acidic cleavage), a focused library of putative dopamine D3 receptor ligands was constructed. The final products revealed good to excellent purity and were screened for binding at monoaminergic G-protein-coupled receptors when selected library members proved to show excellent binding affinity, especially toward the dopamine D3 receptor subtype.
引用
收藏
页码:309 / 316
页数:8
相关论文
共 30 条
  • [1] Alsina J, 1999, CHEM-EUR J, V5, P2787, DOI 10.1002/(SICI)1521-3765(19991001)5:10<2787::AID-CHEM2787>3.0.CO
  • [2] 2-2
  • [3] A modified Backbone Amide Linker (BAL) solid-phase peptide synthesis strategy accommodating prolyl, N-alkylamino acyl, or histidyl derivatives at the C-terminus
    Alsina, J
    Yokum, TS
    Albericio, F
    Barany, G
    [J]. TETRAHEDRON LETTERS, 2000, 41 (38) : 7277 - 7280
  • [4] Backbone amide linker (BAL) strategy for Nα-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of unprotected peptide p-nitroanilides and thioesters
    Alsina, J
    Yokum, TS
    Albericio, F
    Barany, G
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (24) : 8761 - 8769
  • [5] Interactive SAR studies:: Rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists
    Bettinetti, L
    Schlotter, K
    Hübner, H
    Gmeiner, P
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (21) : 4594 - 4597
  • [6] The ortho backbone amide linker (o-BAL) is an easily prepared and highly acid-labile handle for solid-phase synthesis
    Boas, U
    Brask, J
    Christensen, JB
    Jensen, KJ
    [J]. JOURNAL OF COMBINATORIAL CHEMISTRY, 2002, 4 (03): : 223 - 228
  • [7] Attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity by the novel selective dopamine D3-receptor partial agonist FAUC 329 predominantly in the nucleus accumbens of mice
    Boeckler, F
    Leng, A
    Mura, A
    Bettinetti, L
    Feldon, J
    Gmeiner, P
    Ferger, B
    [J]. BIOCHEMICAL PHARMACOLOGY, 2003, 66 (06) : 1025 - 1032
  • [8] Indole resin: A versatile new support for the solid-phase synthesis of organic molecules
    Estep, KG
    Neipp, CE
    Stramiello, LMS
    Adam, MD
    Allen, MP
    Robinson, S
    Roskamp, EJ
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (16) : 5300 - 5301
  • [9] AMEBA: An acid sensitive aldehyde resin for solid phase synthesis
    Fivush, AM
    Willson, TM
    [J]. TETRAHEDRON LETTERS, 1997, 38 (41) : 7151 - 7154
  • [10] BAL resin for the preparation of secondary amines
    Forns, P
    Sevilla, S
    Erra, M
    Ortega, A
    Fernández, JC
    de la Figuera, N
    Fernández-Forner, D
    Albericio, F
    [J]. TETRAHEDRON LETTERS, 2003, 44 (36) : 6907 - 6910