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Title: Novel aryl-alkyl-piperazines with N-acylated amino acids as serotoninergic receptors ligands


The introduction part briefly presented a survey of the combinatorial approaches to generation of hit and lead compounds from libraries targeted on CNS receptors. An efficient solid supported approach to the synthesis of a new class of arylpiperazine derivatives containing Nacylated amino acid residues (Asp, Olu, Asri, Pro) was developed. Two libraries consisting of 132 members were generated on BAL linker functionalized SynPhase™ Lantems. A one-pot cyclization/cleavage step of linkerbound aspartic and glutamic acid derivatives, yielded 3- aminopyrrolidin-2,5-dione and pyrrolidin-5-one-2- carboxamide containing ligands. 17 arylpiperazine derivatives of 3-N-acylaminopyrrolidine- 2,5-dione and N-acyl-prolyl amides (selected on the basis of preliminary screening data) were next synthesized according to the classic solution approach. The compounds evaluated in in vitro tests showed high affinity for the 5-HT1A receptor (K; = 3 -52 nM); however, affinities for the 5-HT2A receptor were diversified (K; = 4.2 -3125 nM). Severa! of the investigated compounds were classified as dual 5-HT1A/5- HT2A receptor ligands. Functional and preclinical in vivo tests allowed selection of derivative 27a (5-HTIA agonist) showing a distinct anxiolytic and antidepressant effect. In the last part, a design and solid-phase synthesis. of a 64-membered library of novel sulfonamide and carboxamide proline derivatives focused on the 5-HT1 receptor antagonist SB-258741 was disclosed. Preliminary 5-HT1 receptor evaluation provided data for further investigations aimed at the search for 5-HT 1 receptor agents.

Level of degree:

2 - studia doktoranckie

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Degree grantor:

Wydział Lekarski


Jean Martinez ; Maciej Pawłowski

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tylko w bibliotece

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Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

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Last modified:

Feb 28, 2022

In our library since:

Nov 21, 2012

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Edition name Date
ZB-102927 Feb 28, 2022


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