Synthesis and structural investigation of some pyrimido[5,4-c]quinolin-4(3H)-one derivatives with a long-chain arylpiperazine moiety as potent 5-HT1A/2A and 5-HT7 receptor ligands

Bojarski, Andrzej J.; Szczesio, Małgorzata; Ołczak, Andrzej; Główka, Marek L.; Mordalski, Stefan; Stańczak, Andrzej

doi:10.1016/j.ejmech.2011.04.060

Cited by 16 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This linker adopts different conformation in both presented crystal structures. Conformation of linker and its influence on the biological activity was widely discussed in the literature 18,[45][46][47][48] . In most known LCAP crystal structures with tetramethylene linker, this aliphatic chain adopts extended conformation (anti-anti-anti) 18 .…”

Section: + -H15ááácl1mentioning

confidence: 99%

Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity

Chłoń-Rzepa

Bucki

Kołaczkowski

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

(2016) Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/ D receptor agents with potential antipsychotic activity, Journal of Enzyme Inhibition and Medicinal Chemistry, 31:6, 1048-1062, DOI: 10.3109/14756366.2015 , 31, 34, 39, 41, 43, 45, and 46 in the functional in vitro evaluation for all targeted receptors showed significant partial D 2 agonist, partial 5-HT 1A agonist, and 5-HT 2A antagonist properties. The advantageous in vitro affinity of compound 34 for 5-HT 1A and D 2 receptors has been explained by means of molecular modeling, taking into consideration its partial agonist activity towards the latter one. In behavioral studies, compounds 32 and 34 revealed antipsychotic-like properties, significantly decreasing D-amphetamine-induced hyperactivity in mice.

show abstract

Section: + -H15ááácl1mentioning

confidence: 99%

Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity

Chłoń-Rzepa

Bucki

Kołaczkowski

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Due to the highly flexible linker (usually 2-4 methylene units), using different experimental and modeling techniques, various attempts have been conducted to determine the bioactive conformation of LCAPs [42]. Assuming that active conformations of LCAPs are closely related to those in solutions or in solid state, two-dimensional (2D) NMR and crystallographic methods were often applied.…”

Section: Main Interactions Of Arylpiperazines With 5-ht 1a Rsmentioning

confidence: 99%

4WD to Travel Inside the 5-HT1A Receptor World

Quaglia¹,

Cifani²,

Bello³

et al. 2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

View full text Add to dashboard Cite

5-HT 1A receptor is one of the most important members of the numerous families of serotoninergic receptors. Though it was the first 5-HT receptor to be identified and cloned, the knowledge of its activation/transduction mechanisms, mediated effects, and connection with other systems is still uncompleted. For this reason, relevant is the study of the four Ws of the title: first of all "who" this receptor is, then "why" it continues to be a so attractive target after several years after its identification, then "where" is 5-HT 1A receptor expressed within the body, and, finally, "what" effects this receptor can elicit under physiological and pathological conditions. Obviously, more and more potent, safe, and selective "drugs" might be discovered once the responses to these questions are given.

show abstract

“…In these studies, this alkyl spacer is frequently composed of two to four methylene units. 15,16) On the other hand, the indole substructure is the basic element in a large number of biologically active natural and synthetic products. In fact, until this day, the indole motif is present in more than 400 drugs and 3000 patents.…”

Section: )mentioning

confidence: 99%

Synthesis, 5-Hydroxytryptamine<sub>1A</sub> Receptor Affinity and Docking Studies of 3-[3-(4-Aryl-1-piperazinyl)-propyl]-1<i>H</i>-Indole Derivatives

Pessoa‐Mahana

Núñez

Araya‐Maturana

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

A series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a-hKey words indolylalkylarylpiperazine; 5-hydroxytryptamine 1A receptor; docking; binding; synthesis Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that mediates various physiological and pathological processes in the peripheral and central nervous system (CNS) by interacting with several different receptors.1-3) The 5-HT 1A receptor sub-population has attracted considerable attention in the drug discovery field.4-7) It is assumed that anxiolytic drugs such as buspirone (1), tandospirone (2), gepirone (3) or ipsapirone (4) (Fig. 1), exert their pharmacological activity through the activation of the 5-HT 1A receptor, where they act as partial agonists.8-10) The 5-HT 1A receptor is also implicated in many other physiopathological CNS processes and conditions such as neuroprotection, schizophrenia, Parkinson's and Alzheimer's diseases, acting alone or associated with other neurotransmitter receptors, especially dopamine receptors.Long-chain arylpiperazine derivatives are one of the most important classes of 5-HT 1A ligands. In general, the arylpiperazine moiety is a good template for drugs acting on many different biological targets, especially CNS receptors.11-13) As a consequence, many compounds containing this scaffold bind with high affinity at 5-HT 1A receptors, but only a few of them also show high selectivity for 5-HT 1A over other receptors. 14)Structure-activity relationship (SAR) studies, performed with numerous generations of arylpiperazine derivatives, showed that CNS activity and both, receptor affinity and selectivity depend basically on the N-1-aryl substituent and a terminal fragment bound to the N-4 atom of the piperazine moiety by an alkyl chain. In these studies, this alkyl spacer is frequently composed of two to four methylene units. 15,16) On the other hand, the indole substructure is the basic element in a large number of biologically active natural and synthetic products. In fact, until this day, the indole motif is present in more than 400 drugs and 3000 patents.17) The range of applications for these therapeutically relevant compounds includes anti-inflammatory drugs, protein kinase C inhibitors, 5-HT agonists and antagonists, melatonin agonists and glucocorticoid receptor modulators.18) Studies on structural modifications of indolylalkylarylpiperazines carried out by Heinrich et al. 14,19) reported a high-affinity pattern for 5-HT 1A agonism and succeeded in optimizing selectivity over dopamine D 2 receptors. This structural pattern considers a C5-substituted indole ring bearing different functional groups and a parasubstituted arylpiperazine. In these studies, a four-carbon atom chain was employed as a linker of both heterocyclic moieties. On the other hand, a few studies on indolylalkylarylpiperazines containing a propyl chain as a linker have been reported regarding their 5-HT 1B/1D receptor affinity. 20,21) However, the influence of a propylic connecting chain on the affinity of this type ...

show abstract

Synthesis and structural investigation of some pyrimido[5,4-c]quinolin-4(3H)-one derivatives with a long-chain arylpiperazine moiety as potent 5-HT1A/2A and 5-HT7 receptor ligands

Cited by 16 publications

References 32 publications

Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity

Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity

4WD to Travel Inside the 5-HT1A Receptor World

Synthesis, 5-Hydroxytryptamine<sub>1A</sub> Receptor Affinity and Docking Studies of 3-[3-(4-Aryl-1-piperazinyl)-propyl]-1<i>H</i>-Indole Derivatives

Contact Info

Product

Resources

About