Synthesis and biological affinity of new imidazo- and indol-arylpiperazine derivatives: further validation of a pharmacophore model for alpha(1)-adrenoceptor antagonists.
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Strappaghetti G, Mastrini L, Lucacchini A, Giannaccini G, Betti L, Fabbrini L
Synthesis and biological affinity of new imidazo- and indol-arylpiperazine derivatives: further validation of a pharmacophore model for alpha(1)-adrenoceptor antagonists.
Bioorg Med Chem Lett. 2008 Sep 15;18(18):5140-5. doi: 10.1016/j.bmcl.2008.07.084. Epub 2008 Jul 24.
- PubMed ID
- 18760923 [ View in PubMed]
- Abstract
In the continuing search for selective alpha(1)-adrenoceptor (AR) antagonists, new alkoxyarylpiperazinylalkylpyridazinone derivatives were designed and synthesized. The new compounds were tested for their affinity toward alpha(1)-AR, alpha(2)-AR and 5-HT(1A) receptors. The ability of these compounds to inhibit the serotonin transporters (SERT) was also determined. The pharmacological data confirm that increasing the size of the ortho alkoxy substituent on the phenyl ring of the arylpiperazine moiety afforded compounds with enhanced affinity toward the alpha(1)-AR. The isopropoxy group, the largest group evaluated, led the best alpha(1)-AR affinity profile. In contrast, the compounds which have an amide group within of the o-alkoxy-phenylpiperazine fragment showed low affinity toward the receptors studied. Similar results were obtained when the amide group was present in the linker of the junction between the two major constituents of the molecule.
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Paroxetine Sodium-dependent serotonin transporter Ki (nM) 0.08 N/A N/A Details