84225-91-2Relevant academic research and scientific papers
Structure-activity relationships of a series of substituted benzamides: Potent D2/5-HT2 antagonists and 5-HT1a agonists as neuroleptic agents
Norman, Mark H.,Rigdon, Greg C.,Hall, William R.,Navas III, Frank
, p. 1172 - 1188 (2007/10/03)
A series of substituted (4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)benzamide derivatives was prepared and evaluated as potential atypical antipsychotic agents. The target compounds were readily prepared from their benzoyl chloride, benzoic acid, or isatoic anhydride precursors, and they were evaluated in vitro for their ability to bind to dopamine D2, serotonin 5-HT2, and serotonin 5-HT1a receptors. To assess the potential antipsychotic activity of these compounds, we investigated their ability to inhibit the apomorphine-induced climbing response in mice. Selected compounds were evaluated further to determine their side-effect potentials. Structure-activity relationships of both mono- and polysubstituted benzamides are discussed herein. While several analogues had potent in vitro and in vivo activities indicative of potential atypical antipsychotic activity, anthranilamide 77 (1192U90) demonstrated a superior pharmacological profile. As a result of this investigation, 1192U90 (2-amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)benzamide hydrochloride) was selected for further evaluation and is currently in phase I clinical trials as a potential atypical antipsychotic agent.
Synthesis of Chiral 5-Substituted 2-Pyrrolidones, Metabolites of the Antipsychotic Benzamides Remoxipride and Raclopride
Gawell, Lars,Stroem, Peter,Hoegberg, Thomas
, p. 981 - 984 (2007/10/02)
Three of the major human metabolites of remoxipride (1) and raclopride (6) have been synthesized in optically active form.Starting from L-pyroglutamic acid, the two pyrrolidones (+)-(5S)-5-(aminomethyl)-2-pyrrolidone (10) and (+)-(5S)-5-(aminomethyl)-1-et
Synthesis of 5-substituted 5-hydroxy-2-pyrrolidones, metabolites of the antipsychotic benzamide remoxipride.
Gawell,Hagberg,Hoegberg,Widman
, p. 476 - 480 (2007/10/02)
This paper describes the synthesis of 5-[(3-bromo-2,6-dimethoxybenzamido)-methyl]-5-hydroxy-2-pyrrolidon e (3) and its 1-ethyl analogue 2, two urinary metabolites of the dopamine D-2 antagonist remoxipride [1, (S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl
Chromatographic Separation of Enantiomers and Barriers to Enantiomerization of Axially Chiral Aromatic Carboxamides
Cuyegkeng, Maria Assunta,Mannschreck, Albrecht
, p. 803 - 810 (2007/10/02)
The enantiomers (M) and (P) of a series of similar aromatic carboxamides have been, for the first time, investigated analytically and enriched preparatively by liquid chromatography on triacetylcellulose.Enantiomeric purities (7-99percent), specific rotations, and barriers to rotation about the C(sp2)-C(sp2) bond (87 - 120 kJ/mol, Table 5) were determined.These energies are discussed in terms of the size of ortho substituents and of the buttressing effects by meta substituents.
Synthesis and neuroleptic activity of substituted benzamides related to metoclopramide
Kumar,De Paulis,Bengtsson,et al.
, p. 1 - 3 (2007/10/02)
Substituted N-(dialkylaminoalkyl)benzamides related to metoclopramide have been synthesized and examined for antagonism of 3H-spiperone receptor binding (in vitro) and the blockade of apomorphine syndrome (in vivo) in the rat. In the series, fo
Potential neuroleptic agents. 3. Chemistry and antidopaminergic properties of substituted 6-methoxysalicylamides
de Paulis,Kumar,Johansson,Raemsby,Florvall,Hall,Angeby-Moeller,Ogren
, p. 1263 - 1269 (2007/10/02)
A series of substituted 6-methoxysalicylamides were synthesized from their corresponding 2,6-dimethoxybenzamides by demethylation of one methoxy group with boron tribromide. Substituted 6-methoxysalicylamides having a lipophilic aromatic substituent in the 3-position para with respect to the methoxy group, e.g. a bromo or an iodo atom or an ethyl or a propyl group, and having an (S)-N-(1-alkyl-2-pyrrolidinyl)methyl moiety as the side chain were found to be potent blockers of [3H]spiperone binding in vitro and potent inhibitors of the apomorphine syndrome in the rat. Similar to remoxipride but in contrast to haloperidol, some of the substituted salicylamides show a 10-20 fold separation between the dose that inhibits hyperactivity and that which inhibits stereotypy. It was concluded that, besides the requirement of a lipophilic substitutent in the position para to the methoxy group for antidopamine activity in vivo, the formation of a coplanar six-membered pseudoring involving the amide moiety and the methoxy group is a structural requirement for activity in vitro.
Potential Neuroleptic Agents. 2,6-Dialkoxybenzamide Derivatives with Potent Dopamine Receptor Blocking Activities
Florvall, Lennart,Oegren, Sven-Ove
, p. 1280 - 1286 (2007/10/02)
A series of some novel N-(1-ethyl-2-pyrrolidinylmethyl)benzamides was synthesized and tested for dopamine receptor blockade in vivo by the ability to block the apomorphine syndrome in the rat.Several compounds were considerably more potent than sulpiride as dopamine receptor blockers and displayed low liability to induce extrapyramidal side effects (catalepsy) in the rat.The blockade of dopamine receptor activity in vivo was mainly confined to the levorotatory isomers having the S absolute configuration.The structure-activity relationships are discussed.
