Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.

Paper

Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.

Published Jul 1, 2003 · J. Obniska, M. Pawłowski, M. Kołaczkowski

Polish journal of pharmacology

UNKNOWN SJR score

18

Citations

0

Influential Citations

Semantic Scholar

Abstract

Novel N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclo-hexanepyrrolidine-2,5-dione (5-7) and 3-spiro-beta-tetralonepyrrolidine-2,5-dione (8-10) were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. All tested compounds exhibited moderate to low 5-HT1A receptor affinity, whereas compounds 5-7 demonstrated high 5-HT2A receptor affinity (Ki = 27, 46 and 15 nM, respectively) and features of 5-HT2A receptor antagonists. Introduction of a beta-tetralone fragment in the 3-position of pyrrolidine-2,5-dione ring (8-10) did not affect 5-HT1A but decreased 5-HT2A receptor affinity.

In Vitro Study

Study Snapshot

New N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione show high 5-HT2A receptor affinity and potential as 5-HT2A receptor antagonists.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.

Sign up to use Study Snapshot

References

Serotonin receptor and transporter ligands - current status.

Recent development of serotonin receptor- and transporter-specific ligands has led to improved therapeutic and diagnostic properties in various human diseases.

Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines.

Substituted 1,2,3,4-tetrahydro-beta-carbolines show similar 5-HT1A and 5-HT2 receptor affinity, with pharmacophores adopting common positions in the 5-HT1A receptor model.

Selectivity of serotonergic drugs for multiple brain serotonin receptors. Role of [3H]-4-bromo-2,5-dimethoxyphenylisopropylamine ([3H]DOB), a 5-HT2 agonist radioligand.

Using antagonist radioligands to label 5-HT2 receptors and agonist radioligands to label 5-HT1 receptors may overestimate the selectivity of serotonergic drugs, potentially impacting drug development.

Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.

The inhibition constant (K1) of a substance is equal to the concentration of inhibitor required to produce 50% inhibition of an enzyme reaction under either noncompetitive or uncompetitive inhibition kinetics.

Citations

VIRTUAL TOXICITY AND DRUG LIKENESS OF NEWLY SYNTHESIZED METHYLXANTHINES WITH N1 ARYLPIPERAZINE MOIETY

Newly synthesized methylxanthines with an arylpiperazine moiety at N1 show moderate toxicity and high drug likeness, making them suitable for future optimizations.

1-Benzyl-3′-[(1H-indol-3-yl)carbonyl]-1′-methyl-2-oxo-4′-(pyridin-3-yl)spiro[indoline-3,2′-pyrrolidine]-3′-carbonitrile

This compound exhibits an envelope conformation with the N atom as the flap, and exhibits a dihedral angle of 75.09 (11)° between the benzene and pyridine rings.

Synthesis, computational studies and preliminary pharmacological evaluation of 2-[4-(aryl substituted) piperazin-1-yl]-N-benzylacetamides as potential antipsychotics

Compound 3b shows potential as an atypical antipsychotic-like profile, showing good similarity to standard drugs clozapine, ketanserin, and risperidone.

Crystal structure of ethyl 2′′,3-dioxo-7′,7a’-dihydro-1′H,3H,3′H-dispiro[benzo[b]thiophene-2,6′-pyrrolo[1,2-c]thiazole-5′,3′′-indoline]-7′-carboxylate

The title compound exhibits a unique crystal structure with a central pyrrolidine ring and various hydrogen bonds, forming a three-dimensional structure.

Ethyl 27-oxo-15-oxa-2,20-diazahexacyclo[18.6.1.01,8.02,6.09,14.021,26]heptacosa-9,11,13,21,23,25-hexaene-7-carboxylate

This compound exhibits a twisted conformation and a graph-set motif, with a dihedral angle of 81.7 (8)° and a disordered terminal ethyl group.

Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro-beta-tetralonepyrrolidine-2,5-dione.

Sign up to use Study Snapshot

References

Serotonin receptor and transporter ligands - current status.

Recent development of serotonin receptor- and transporter-specific ligands has led to improved therapeutic and diagnostic properties in various human diseases.

Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines.

Substituted 1,2,3,4-tetrahydro-beta-carbolines show similar 5-HT1A and 5-HT2 receptor affinity, with pharmacophores adopting common positions in the 5-HT1A receptor model.

Selectivity of serotonergic drugs for multiple brain serotonin receptors. Role of [3H]-4-bromo-2,5-dimethoxyphenylisopropylamine ([3H]DOB), a 5-HT2 agonist radioligand.

Using antagonist radioligands to label 5-HT2 receptors and agonist radioligands to label 5-HT1 receptors may overestimate the selectivity of serotonergic drugs, potentially impacting drug development.

Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.

The inhibition constant (K1) of a substance is equal to the concentration of inhibitor required to produce 50% inhibition of an enzyme reaction under either noncompetitive or uncompetitive inhibition kinetics.

Citations

VIRTUAL TOXICITY AND DRUG LIKENESS OF NEWLY SYNTHESIZED METHYLXANTHINES WITH N1 ARYLPIPERAZINE MOIETY

Newly synthesized methylxanthines with an arylpiperazine moiety at N1 show moderate toxicity and high drug likeness, making them suitable for future optimizations.

1-Benzyl-3′-[(1H-indol-3-yl)carbon­yl]-1′-methyl-2-oxo-4′-(pyridin-3-yl)spiro­[indoline-3,2′-pyrrolidine]-3′-carbo­nitrile

This compound exhibits an envelope conformation with the N atom as the flap, and exhibits a dihedral angle of 75.09 (11)° between the benzene and pyridine rings.

Synthesis, computational studies and preliminary pharmacological evaluation of 2-[4-(aryl substituted) piperazin-1-yl]-N-benzylacetamides as potential antipsychotics

Compound 3b shows potential as an atypical antipsychotic-like profile, showing good similarity to standard drugs clozapine, ketanserin, and risperidone.

Crystal structure of ethyl 2′′,3-dioxo-7′,7a’-dihydro-1′H,3H,3′H-dispiro[benzo[b]thiophene-2,6′-pyrrolo[1,2-c]thiazole-5′,3′′-indoline]-7′-carboxylate

The title compound exhibits a unique crystal structure with a central pyrrolidine ring and various hydrogen bonds, forming a three-dimensional structure.

Ethyl 27-oxo-15-oxa-2,20-diazahexacyclo[18.6.1.01,8.02,6.09,14.021,26]heptacosa-9,11,13,21,23,25-hexaene-7-carboxylate

This compound exhibits a twisted conformation and a graph-set motif, with a dihedral angle of 81.7 (8)° and a disordered terminal ethyl group.

1-Benzyl-3′-[(1H-indol-3-yl)carbonyl]-1′-methyl-2-oxo-4′-(pyridin-3-yl)spiro[indoline-3,2′-pyrrolidine]-3′-carbonitrile