Fused azaindole derivatives: molecular design, synthesis and in vitro pharmacology leading to the preferential dopamine D3 receptor agonist FAUC 725.
Article Details
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Lober S, Hubner H, Gmeiner P
Fused azaindole derivatives: molecular design, synthesis and in vitro pharmacology leading to the preferential dopamine D3 receptor agonist FAUC 725.
Bioorg Med Chem Lett. 2002 Sep 2;12(17):2377-80.
- PubMed ID
- 12161137 [ View in PubMed]
- Abstract
Computational studies based on the similarity of molecular electrostatic potential maps initiated the synthesis of the tricyclic target compounds 1 (FAUC 725) and 2. Receptor binding studies at the dopamine receptor subtypes D1, D2(long), D2(short), D3 and D4 showed that the azaindole 1 revealed D3 affinity (K(i)=0.54 nM) comparable to the lead pramipexole and enhanced selectivity over D2 and D4. Mitogenesis experiments indicated substantial intrinsic activity for the D3 selective dipropylamine 1. Based on the structure of (S)-3-PPP, bioisosteric replacement and conformational restriction leading to the test compound 2 was not fruitful.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Pramipexole Dopamine D2 receptor Ki (nM) 40 N/A N/A Details Pramipexole Dopamine D2 receptor Ki (nM) 27 N/A N/A Details Pramipexole Dopamine D3 receptor EC 50 (nM) 1.5 N/A N/A Details Pramipexole Dopamine D3 receptor Ki (nM) 0.87 N/A N/A Details Pramipexole Dopamine D4 receptor Ki (nM) 8.5 N/A N/A Details Pramipexole Dopamine D4 receptor EC 50 (nM) 15 N/A N/A Details