Potential antipsychotic agents. 7. Synthesis and antidopaminergic properties of the atypical highly potent (S)-5-bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide and related compounds. A comparative study.

  title={Potential antipsychotic agents. 7. Synthesis and antidopaminergic properties of the atypical highly potent (S)-5-bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide and related compounds. A comparative study.},
  author={Thomas H{\"o}gberg and Tomas de Paulis and Lars George Johansson and Yatendra Kumar and H. Hall and Sven Ove Ogren},
  journal={Journal of medicinal chemistry},
  volume={33 8},
(S)-5-Bromo-2,3-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (6) and some related compounds, i.e. the R isomer 7, the 3-hydroxy analogue 8, the desbromo derivative 9, the monomethoxy compound 10, and the 2,4-dimethoxy analogue 11, have been synthesized from the corresponding benzoic acids. The benzamides, lacking o-hydroxy groups, were evaluated for their affinity for the [3H]spiperone binding site and for their inhibition of apomorphine-induced behavioral responses in relation to the… Expand
27 Citations
Synthesis and binding properties of the fluorinated substituted benzamide [3H]NCQ 115, a new selective dopamine D2 receptor ligand.
It can be concluded that [3H]NCQ 115 binds to dopamine D2 receptors in the rat striatum with high affinity and high selectivity and may be a suitable ligand for positron emission tomography studies of the human brain in vivo. Expand
Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors
Crystal structures of three inhibitors (compounds (−)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors. Expand
Facile Preparation of (S)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxy-5-(tributyltin)benzamide from Isoremoxipride: The Precursor of [125I]- and [123I]Epidepride
Abstract [125I]Epidepride, (S)-(−)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[125I]iodo-2,3-dimethoxybenzamide ([125I]NCQ 219), is a new, extremly potent radioligand, useful in the study of theExpand
Ligands for the dopamine D 2-like receptors
The hypothesis that compounds which selectively antagonize the dopamine (DA) D4 receptor will provide new atypical antipsychotics has mainly been fueled by two observations: The preferential blockadeExpand
Preparation of [123I]‐ and [125I]epidepride: A dopamine D‐2 receptor antagonist radioligand
(S)-(−)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[123I]iodo-2,3-dimethoxybenzamide (TDP 517) (proposed generic name, [123I]epidepride) is the iodine-123 substituted analogue of isoremoxipride (FLB 457),Expand
Aromatic and amine substituent effects on the apparent lipophilicities of N-[(2-pyrrolidinyl)methyl]-substituted benzamides.
Lipophilic properties of 92 dopamine D-2 receptor antagonists belonging to the substituted benzamide class of compounds were determined by octadecylsilane reversed-phase HPLC and multiple regression analysis showed that log kwo can be expressed as the sum of pi contributions and a cross correlation term (sigma rho sigma) for interactions between the aromatic substituents. Expand
[11C]cyclopropyl-FLB 457: a PET radioligand for low densities of dopamine D2 receptors.
(S)-5-bromo-N-[(1-cyclopropylmethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxybenzamide (4), synthesized by using [(11)C]methyltriflate in a methylation reaction with its phenolic precursor with good incorporation yield and high specific radioactivity, is a promising radioligand for imaging D(2) receptors in low density regions in brain. Expand
High affinity dopamine D2 receptor radioligands. 2. [125I]epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors.
Epidepride, (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide+ ++, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist.Expand
NCQ 298, a new selective iodinated salicylamide ligand for the labelling of dopamine D2 receptors
The specific properties of [123I]NCQ 298 suggest that this compound is a useful ligand for quantitative SPECT studies of dopamine D2 receptors in man. Expand
A comparative PET-study of five carbon-11 or fluorine-18 labelled salicylamides. Preparation and in vitro dopamine D-2 receptor binding.
  • C. Halldin, L. Farde, +4 authors O. Solin
  • Chemistry, Medicine
  • International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
  • 1991
Five 11C- or 18F-labelled salicylamides prepared and examined in vitro and found that with both analogs I and II there was a high uptake in the striatum, a region with a high density of dopamine D-2 receptors, whereas the affinity of NCQ 135 was similar to that of eticlopride. Expand