154060-79-4Relevant academic research and scientific papers
N-(ω)-(4-(2-methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands
Hackling, Anneke,Ghosh, Robin,Perachon, Sylvie,Mann, André,H?ltje, Hans-Dieter,Wermuth, Camille G.,Schwartz, Jean-Charles,Sippl, Wolfgang,Sokoloff, Pierre,Stark, Holger
, p. 3883 - 3899 (2007/10/03)
The dopamine D3 receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D3 versus D2 receptor-preferring ligands, the parti
N-aryl-N'-benzylpiperazines as potential antipsychotic agents
Reitz,Baxter,Bennett,Codd,Jordan,Malloy,Maryanoff,McDonnell,Ortegon,Renzi,Scott,Shank,Sherrill,Vaught,Wustrow
, p. 4211 - 4222 (2007/10/03)
N1-(2-Alkoxyphenyl)piperazines additionally containing an N4-benzyl group bearing alcohol, amide, imide, or hydantoin functionalities were prepared and evaluated in the conditioned avoidance response (CAR) test predictive of clinical antipsychotic activity and in in vitro receptor- binding assays. Certain of the compounds display high affinity for the D2, 5-HT(1A), and α1-adrenergic receptors. Structures bearing acyclic amide, lactam, and imide fuctionalities display good biological activity, with a preference for the 1,3-disubstituted phenyl ring relative to the 1,4- and 1,2-congeners (7 vs 10 and 12). Every possible position of hydantoin attachment was investigated (e.g., substitution at N1, N3, and C5). The hydantoin involving attachment to N1 (24) was found to have good biological activity, whereas those hydantoins with attachment to N3 or C5 (22, 23, and 25) were inactive. Several of the smaller acetylated derivatives (30 and 33) have fair in vivo activity, which was lost in the case of the larger benzoyl analog 31. Uracil congener 34 had modest affinity for the D2 receptor (65 nM) as well as excellent in vivo activity. Benzylamino compounds display (viz. 27 and 35-38) moderate CAR activity but have surprising receptor affinity, often greater than those of comparable structures bearing a carbonyl (36 vs 7). Benzyl and benzhydryl alcohol compounds 40-48 are more active than amino structures 27 and 35-38 and also exhibit excellent in vivo activity in the CAR test with modest D2 and 5-HT(1A) receptor binding.
