1.
Bioorg Med Chem Lett
; 17(2): 400-5, 2007 Jan 15.
Article
in English
| MEDLINE
| ID: mdl-17084080
ABSTRACT
A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D2/D3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability.
Subject(s)
Antipsychotic Agents/chemical synthesis , Antipsychotic Agents/pharmacology , Alkylation , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/metabolism , Dopamine Antagonists/chemical synthesis , Dopamine Antagonists/pharmacology , Dopamine D2 Receptor Antagonists , Drug Design , Humans , Receptor, Serotonin, 5-HT2A/drug effects , Receptor, Serotonin, 5-HT2C/drug effects , Receptors, Dopamine D3/antagonists & inhibitors , Receptors, Serotonin/drug effects , Recombinant Proteins/drug effects , Serotonin Antagonists/chemical synthesis , Serotonin Antagonists/pharmacology , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology
2.
Bioorg Med Chem Lett
; 13(6): 1055-8, 2003 Mar 24.
Article
in English
| MEDLINE
| ID: mdl-12643910
ABSTRACT
Novel 5-HT(7) receptor antagonists containing the benzocycloheptanone core were identified from high throughput screening. Molecular modelling and SAR studies have converted these intractable hits into a more potent, selective and tractable series, exemplified by compound (25), SB-691673.
