Synthesis and Preliminary Pharmacological Evaluation of 4´-Arylmethyl Analogues of Clozapine. I. The Effect of Aromatic Substituents

2002 ◽  
Vol 55 (9) ◽  
pp. 565 ◽  
Author(s):  
B. Capuano ◽  
I. T. Crosby ◽  
E. J. Lloyd ◽  
D. A. Taylor
Keyword(s):  
Chemical Synthesis ◽  
Atypical Antipsychotic ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Research Program ◽  
Structural Modification ◽  
Antagonist Activity ◽  
Pharmacological Evaluation ◽  
Binding Data ◽  
Positional Effects

As part of a research program to develop compounds with mixed dopamine D4 and serotonin 5-HT2A antagonist activity with potential for the treatment of schizophrenia, we report a family of compounds based on structural modification of the atypical antipsychotic, clozapine (2). The chemical synthesis, structural characterization and pharmacological evaluation of a series 4�-arylmethyl analogues of clozapine are described. Preliminary receptor binding data are presented, examining primarily the electronic and positional effects of substituents on the introduced arylmethyl group, and secondarily the nature of the aryl ring.

Synthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogues of Clozapine. III. Replacement of the Tricyclic Nucleus with a Bicyclic Template

2007 ◽  
Vol 60 (12) ◽  
pp. 928 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
David A. Taylor
Keyword(s):  
Nitrogen Atom ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Research Program ◽  
Substituent Effects ◽  
Bicyclic Compounds ◽  
Degree Of Unsaturation ◽  
Selection Of

As a continuing part of our research program in search of novel compounds for the treatment of schizophrenia, we report the synthesis and preliminary receptor binding affinity for a series of bicyclic analogues of clozapine derived from a selection of promising tricyclic candidates published previously. These bicyclic compounds investigate some substituent effects and the length and nature of the linker between an ionizable nitrogen atom at physiological pH and the introduced aryl moiety. The chemistry, structural characterization, and in vitro evaluation are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and selected substituents coupled to the bicyclic nucleus are discussed in relation to affinity for dopamine D4 and serotonin 5-HT2A receptors.

Aminimides as Potential CNS Acting Agents. II Design, Synthesis, and Receptor Binding of 4′-Arylalkyl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

2008 ◽  
Vol 61 (1) ◽  
pp. 5 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
Juliette E. Neve ◽  
David A. Taylor
Keyword(s):  
Atypical Antipsychotic ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Marked Reduction ◽  
Second Generation ◽  
Functional Group ◽  
Design Synthesis ◽  
Biochemical Effects ◽  
Antipsychotic Activity

We report the synthesis of a series of second generation aminimide-based analogues of clozapine, investigating the length of the linker between the aminimide functional group and the introduced aryl moiety. The chemistry and structural characterization of this series of 4′-arylalkyl aminimide analogues of clozapine are described. Preliminary findings on the biochemical effects of linker length and type of aryl moiety on affinity for dopamine D4 and serotonin 5-HT2A receptors are discussed. All of the compounds showed a marked reduction in binding at the two receptors when compared with clozapine, thus showing a reduced potential for atypical antipsychotic activity.

Synthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogues of Clozapine. IV. The Effects of Aromaticity and Isosteric Replacement

2008 ◽  
Vol 61 (12) ◽  
pp. 930 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
Anna Podloucka ◽  
David A. Taylor
Keyword(s):  
Receptor Binding ◽  
Pharmacological Activity ◽  
Structural Characterization ◽  
Structural Model ◽  
Antipsychotic Agents ◽  
Pharmacological Effects ◽  
Aryl Group ◽  
Preliminary Results ◽  
Pharmacological Evaluation

We report the synthesis and preliminary pharmacological activity of a new series of tricyclic analogues of clozapine as potential antipsychotic agents for the treatment of schizophrenia. These compounds were designed based on a revised structural model, and investigate the length and nature of a designated linker (alkyl and alkyloxy) and the nature of the introduced aryl group (aromatic and heteroaromatic). The chemistry and structural characterization of this series of 4′-arylalkyl(oxy) analogues of clozapine are described. Preliminary results on the pharmacological effects of the selected linkers and introduced aryl groups on affinity for dopamine D4 and serotonin 5-HT2A receptors are discussed. Psychosis-related animal behavioural data for promising compounds identified from the receptor binding screen are also presented.

Chemical Synthesis and Preliminary Structural Characterization of a Nitrous Acid Interstrand Cross-Linked Duplex DNA

1999 ◽  
Vol 121 (21) ◽  
pp. 5081-5082 ◽  
Author(s):  
Eric A. Harwood ◽  
Snorri Th. Sigurdsson ◽  
N. B. Fredrik Edfeldt ◽  
Brian R. Reid ◽  
Paul B. Hopkins
Keyword(s):  
Chemical Synthesis ◽  
Structural Characterization ◽  
Nitrous Acid ◽  
Duplex Dna

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

1997 ◽  
Vol 24 (3) ◽  
pp. 316-319 ◽  
Author(s):  
Bernd Johannsen ◽  
Ralf Berger ◽  
Peter Brust ◽  
Hans-Juergen Pietzsch ◽  
Matthias Scheunemann ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structural Modification ◽  
Brain Uptake ◽  
Technetium 99M

Ketanserin Analogs: The Effect of Structural Modification on 5-HT2 Serotonin Receptor Binding

1995 ◽  
Vol 38 (7) ◽  
pp. 1196-1202 ◽  
Author(s):  
Abd M. Ismaiel ◽  
Kim Arruda ◽  
Milt Teitler ◽  
Richard A. Glennon
Keyword(s):  
Receptor Binding ◽  
Structural Modification ◽  
Serotonin Receptor ◽  
Serotonin Receptor Binding

The synthesis and receptor binding affinities of DDD-016, a novel, potential, atypical antipsychotic

MedChemComm ◽  
2012 ◽  
Vol 3 (5) ◽  
pp. 580 ◽  
Author(s):  
Achintya Bandyopadhyaya ◽  
Desikan R. Rajagopalan ◽  
Nigam P. Rath ◽  
Amy Herrold ◽  
Raghavan Rajagopalan ◽  
...  
Keyword(s):  
Atypical Antipsychotic ◽  
Receptor Binding ◽  
Binding Affinities
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