High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships

Modica, Maria; Santagati, Maria; Russo, Filippo; Selvaggini, C.; Cagnotto, Alfredo; Mennini, Tiziana

doi:10.1016/s0223-5234(00)00175-6

Cited by 31 publications

(9 citation statements)

References 13 publications

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“…The studied compounds are 153 5-HT 1A selective ligands, which were taken from the literature [1,11–16] and their generic structures are shown in Figure 1. The inhibition constant ( K i ) is obtained from the IC 50 value by the Cheng-Prusoff equation [39].…”

Section: Experimental and The Theory Of The Modeling Methodsmentioning

confidence: 99%

“…Hence, strategies discriminating the above sources of serotonergic tone will also contribute to the in vivo assessment of inverse agonist [12], agonist or antagonist effects, with 5-HT 1A receptors being a good candidate considering their tone as well as pre- and postsynaptic localization. Several potent 5-HT 1A ligands belong to different chemical classes such as arylpiperazine compounds [13], 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles [14], piperazine-pyridazinone derivatives [15], [[(arylpiperazinyl) alkyl]thio]thieno[2,3-d]pyrimidinone derivatives [16], 3-[(4-aryl) piperazin-1-yl]-1-arylpropane derivatives [17], 4-[2-(3-methoxyphenyl) ethyl]-1-(2-methoxyphenyl) piperazine [18], and arylpiperazinylalkylthiobenzimidazole, benzothiazole, or benzoxazole derivatives [1]. …”

Section: Introductionmentioning

confidence: 99%

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Classification of 5-HT1A Receptor Ligands on the Basis of Their Binding Affinities by Using PSO-Adaboost-SVM

Cheng

Zhang

Zhou

et al. 2009

IJMS

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In the present work, the support vector machine (SVM) and Adaboost-SVM have been used to develop a classification model as a potential screening mechanism for a novel series of 5-HT1A selective ligands. Each compound is represented by calculated structural descriptors that encode topological features. The particle swarm optimization (PSO) and the stepwise multiple linear regression (Stepwise-MLR) methods have been used to search descriptor space and select the descriptors which are responsible for the inhibitory activity of these compounds. The model containing seven descriptors found by Adaboost-SVM, has showed better predictive capability than the other models. The total accuracy in prediction for the training and test set is 100.0% and 95.0% for PSO-Adaboost-SVM, 99.1% and 92.5% for PSO-SVM, 99.1% and 82.5% for Stepwise-MLR-Adaboost-SVM, 99.1% and 77.5% for Stepwise-MLR-SVM, respectively. The results indicate that Adaboost-SVM can be used as a useful modeling tool for QSAR studies.

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Section: Experimental and The Theory Of The Modeling Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Classification of 5-HT1A Receptor Ligands on the Basis of Their Binding Affinities by Using PSO-Adaboost-SVM

Cheng

Zhang

Zhou

et al. 2009

IJMS

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“…for C 9 H 13 N 7 O 2 S: C, 38.16; H, 4.59;N,34.63;S,11.31. Found: C,38.03;H,4.75;N,34.24;S,pyrimidin-4(3H)-one (14).…”

Section: 3-dihydro-3-(2-aminoethyl)-2-thioxo-56-dimethyl-1h-thienomentioning

confidence: 99%

“…In this work, we report the synthesis of new N3-substituted-2-thioxothieno [2,3-d]pyrimidinone derivatives (8)(9)(10)(11)(12) and of new 2,3-diamino unsubstituted and substituted thieno [2,3-d]pyrimidinone derivatives (13)(14)(15)(16)(17); intermediates 13-17 were used for the preparation of remarkably interesting new compounds both from a chemical and pharmacological viewpoint such as the thieno [2,3-d]- [1,2,4]triazolo [1,5-a]pyrimidinone (18)(19)(20)(21), the thieno- [2,3-d] [1,2,4]triazolo [4,3-a]pyrimidinone (25, 29 and 30) and the thieno [2',3':4,5]pyrimido [1,2-b] [1,2,4,5]tetrazin-9-one (26-28) derivatives. The synthetic procedures used in this paper are reported in Schemes 1 and 2.…”

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Synthesis of new thienotriazolopyrimidine and thienopyrimidotetrazine derivatives from bifunctional intermediates

Modica

Santagati

2001

Journal of Heterocyclic Chem

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New compounds containing the thienotriazolopyrimidine and thienopyrimidotetrazine skeleton are prepared from the bifunctional intermediates 2,3-diamino-5,6-dimethylthieno [2,3-d]pyrimidin-4(3H)-one derivatives 13-17. The 2,pyrimidin-4(1H)-one derivatives 8-12 are also prepared.J. Heterocyclic Chem., 38, 973 (2001).For a long time, our research group has been interested in the synthesis of heterocyclic condensed derivatives, with the aim of evaluating their pharmacological activity, such as analgesic, anti-inflammatory [1-6] and anti-convulsive [7].In recent works, we described the preparation of 3-amino-2-thioxothieno[2,3-d]pyrimidinone [1,8] and of 3-amino-2-phenylaminothieno[2,3-d]pyrimidinone derivatives [7] which are versatile intermediates of bridgehead nitrogen polyheterocycles for the presence of two adjacent reactive functional groups. Through these intermediates, we obtained thiazolothienopyrimidines, thienopyrimidothiadiazoles, thienopyrimidothiadiazines, thienopyrimidotetrazines and thienotriazolopyrimidines [1][2][3][4][5][6][7][8][9].In this work, we report the synthesis of new N3-substituted-2-thioxothieno The reaction of the isothiocyanate 1 [10] in dichloromethane at room temperature with an ammonium hydroxide solution, with propylamine or methoxycarbonylhydrazine gave the derivatives 2, 5, and 7, respectively.The 2-thioxo derivatives 8-11 were obtained from compounds 2, 4 [11], 5, and 7, respectively, by refluxing in an ethanolic potassium hydroxide solution, followed by acidification of the aqueous suspension of the separated solids. Compounds 8 and 11 are identical with those obtained by other synthetic routes [12,13]. Compound 12 was obtained from the isothiocyanate 1 with ethylenediamine under the same experimental conditions adopted for the synthesis of derivatives 2, 5, and 7. By reaction of compounds 2 and 3 [13] with hydrazine hydrate were prepared the 2,3-diamino derivative 13 and the 2-methylamino derivative 15, respectively. The 2-amino-3-methylamino derivative 14 was 973

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Synthesis and Receptor Binding of New Thieno[2,3‐d]‐pyrimidines as Selective Ligands of 5‐HT₃Receptors

Modica¹,

Romeo

Salerno

et al. 2008

Archiv der Pharmazie

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With the aim to develop new potent and selective ligands of 5-HT(3)-type serotonin receptors and to acquire more information on their structure-affinity relationships, new thieno[2,3-d]pyrimidine derivatives 32-39 were synthesized and their binding to 5-HT(3) versus 5-HT(4 )receptors was studied. Some of these new compounds exhibit good affinity for cortical 5-HT(3) receptors, but not for 5-HT(4) receptors. Among these derivatives, 6-ethyl-4-(4-methyl-1-piperazinyl)-2-(methylthio)thieno[2,3-d]pyrimidine 32 is the most potent ligand (K(i) = 67 nM); it behaves as a competitive antagonist of the 5-HT(3) receptor function in the guinea pig colon. Its binding interactions with 5-HT(3A )receptors were analysed by using receptor modelling and comparative docking.

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High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships

Cited by 31 publications

References 13 publications

Classification of 5-HT1A Receptor Ligands on the Basis of Their Binding Affinities by Using PSO-Adaboost-SVM

Classification of 5-HT1A Receptor Ligands on the Basis of Their Binding Affinities by Using PSO-Adaboost-SVM

Synthesis of new thienotriazolopyrimidine and thienopyrimidotetrazine derivatives from bifunctional intermediates

Synthesis and Receptor Binding of New Thieno[2,3‐d]‐pyrimidines as Selective Ligands of 5‐HT₃Receptors

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High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships

Cited by 31 publications

References 13 publications

Classification of 5-HT1A Receptor Ligands on the Basis of Their Binding Affinities by Using PSO-Adaboost-SVM

Classification of 5-HT1A Receptor Ligands on the Basis of Their Binding Affinities by Using PSO-Adaboost-SVM

Synthesis of new thienotriazolopyrimidine and thienopyrimidotetrazine derivatives from bifunctional intermediates

Synthesis and Receptor Binding of New Thieno[2,3‐d]‐pyrimidines as Selective Ligands of 5‐HT3 Receptors

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Synthesis and Receptor Binding of New Thieno[2,3‐d]‐pyrimidines as Selective Ligands of 5‐HT₃Receptors