Synthesis, Structural and Thermal Studies of 3-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-ethoxy-1H-indole (D2AAK1_3) as Dopamine D2 Receptor Ligand
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Affinity to the Dopamine D2 Receptor
2.3. X-ray Analysis
2.4. Molecular Modeling
2.5. Thermal Analysis
3. Materials and Methods
3.1. Chemistry
3.2. In Vitro D2 Receptor Binding Assay
3.3. X-ray Structure Analysis
3.4. Molecular Modeling
3.4.1. Compound Preparation
3.4.2. Molecular Docking
3.4.3. Molecular Dynamics
3.5. Thermal Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compound are available from the authors. |
Formula | C22H24N2O |
Formula weight | 332.43 |
Temperature K | 293(2) |
Crystal system | orthorhombic |
Space group | P212121 |
a (Å) | 5.9600(4) |
b (Å) | 15.0986(9) |
c (Å) | 16.1571(9) |
Volume (Å3) | 1814.5(2) |
Z | 4 |
Calculated density (g cm−3) | 1.217 |
μ (mm−1) | 0.075 |
Absorption correction | multi-scan |
F(000) | 712 |
Crystal size (mm) | 0.50 × 0.20 × 0.20 |
θ range (°) | 2.698 to 27.103 |
Index ranges | −7 ≤ h ≤ 7 −19 ≤ k ≤ 19 −25 ≤ l ≤ 18 |
Reflections collected/unique | 14,278/3993 |
Rint | 0.0442 |
Data/restraints/parameters | 3993/0/231 |
GooF on F2 | 1.000 |
Final R indices[I > 2σ(I)] | R1 = 0.0437, wR2 = 0.0887 |
R indices(all data) | R1 = 0.0745, wR2 = 0.1019 |
Largest diff. peak/hole, e Å−3 | 0.156/−0.111 |
Bond Lengths (Å) | |||
C1-N1 | 1.359(3) | C10-C11 | 1.364(5) |
C1-C2 | 1.369(3) | C11-C12 | 1.376(4) |
C2-C15 | 1.441(3) | C13-N2 | 1.462(3) |
C2-C3 | 1.465(3) | C13-C14 | 1.497(3) |
C3-C14 | 1.325(3) | C15-C22 | 1.406(3) |
C3-C4 | 1.506(3) | C15-C16 | 1.409(3) |
C4-C5 | 1.512(3) | C16-C17 | 1.373(4) |
C5-N2 | 1.459(3) | C17-O1 | 1.380(3) |
C6-N2 | 1.472(3) | C17-C20 | 1.392(4) |
C6-C7 | 1.503(3) | C18-O1 | 1.416(3) |
C7-C8 | 1.376(3) | C18-C19 | 1.493(4) |
C7-C12 | 1.383(3) | C20-C21 | 1.366(4) |
C8-C9 | 1.379(4) | C21-C22 | 1.386(4) |
C9-C10 | 1.360(4) | C22-N1 | 1.376(3) |
Bond angles (°) | |||
C14-C3-C2 | 124.6(2) | C3-C14-C13 | 124.1(2) |
C14-C3-C4 | 118.6(2) | C16-C17-O1 | 124.3(2) |
C2-C3-C4 | 116.7(2) | O1-C17-C20 | 114.6(2) |
C3-C4-C5 | 113.0 (2) | C5-N2-C13 | 108.4(2) |
N2-C5-C4 | 111.0(2) | C5-N2-C6 | 111.2(2) |
N2-C6-C7 | 114.1(2) | C13-N2-C6 | 107.7(2) |
N2-C13-C14 | 113.1(2) | C17-O1-C18 | 118.0(2) |
Torsion angles (°) | |||
C4-C5-N2-C13 | −65.0(3) | C4-C3-C14-C13 | 0.6(4) |
C3-C4-C5-N2 | 47.6(3) | N2-C13-C14-C3 | −18.2(4) |
C14-C3-C4-C5 | −15.0(3) | C14-C13-N2-C5 | 49.2(3) |
Hydrogen Bond [Å, °] | ||||
D-H···A | d(D-H) | d(H···A) | d(D···A) | DHA |
N1-H1N···N2 i | 0.88(3) | 2.41(3) | 3.217(3) | 154(2) |
C-H···Cg interactions [Å, °] | ||||
C-H···Cg | d(D-H) | d(H···Cg) | d(C···Cg) | CHCg |
C4-H4B···Cg1 ii | 0.97 | 2.94 | 3.567(3) | 124 |
C19-H19C···Cg4 iii | 0.96 | 3.00 | 3.799(3) | 142 |
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Kondej, M.; Bartyzel, A.; Pitucha, M.; Wróbel, T.M.; Silva, A.G.; Matosiuk, D.; Castro, M.; Kaczor, A.A. Synthesis, Structural and Thermal Studies of 3-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-ethoxy-1H-indole (D2AAK1_3) as Dopamine D2 Receptor Ligand. Molecules 2018, 23, 2249. https://doi.org/10.3390/molecules23092249
Kondej M, Bartyzel A, Pitucha M, Wróbel TM, Silva AG, Matosiuk D, Castro M, Kaczor AA. Synthesis, Structural and Thermal Studies of 3-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-ethoxy-1H-indole (D2AAK1_3) as Dopamine D2 Receptor Ligand. Molecules. 2018; 23(9):2249. https://doi.org/10.3390/molecules23092249
Chicago/Turabian StyleKondej, Magda, Agata Bartyzel, Monika Pitucha, Tomasz M. Wróbel, Andrea G. Silva, Dariusz Matosiuk, Marián Castro, and Agnieszka A. Kaczor. 2018. "Synthesis, Structural and Thermal Studies of 3-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-ethoxy-1H-indole (D2AAK1_3) as Dopamine D2 Receptor Ligand" Molecules 23, no. 9: 2249. https://doi.org/10.3390/molecules23092249