Skip to main content
. 2012 Feb 7;7(3):483–494. doi: 10.1002/cmdc.201100546

Table 1.

Pharmacophore model search results from the new and old D1 agonist pharmacophore models using two different conformational ensembles of the set of active and inactive ligands.

New pharmacophore model Old pharmacophore model
Ligand MOE stochastic search Born solvation MMFF94(S)[a] MacroModel serial torsion search GB/SA solvation OPLS2005[b] MOE stochastic search Born solvation MMFF94(S)[a] MacroModel serial torsion search GB/SA solvation OPLS2005[b]
ΔE[c] RMSD[d] #c/#h[e] ΔE[c] RMSD[d] #c/#h[e] ΔE[c] RMSD[d] #c/#h[e] ΔE[c] RMSD[d] #c/#h[e]
Doxanthrine Full 0.5 0.60 2/1 0.0 0.11 14/14 0.0 0.12 2/2 0.0 0.11 14/6
SKF89626 Full 0.1 0.61 4/2 0.0 0.63 20/6 0.1 0.61 4/2 0.0 0.63 20/6
(−)-A86929 Full 0.0 0.54 10/6 0.0 0.52 73/58 0.0 0.54 10/10 0.5 0.12 73/36
A77636 Full 1.4 0.30 3/1 0.0 0.26 11/7 0.0 0.28 3/2 0.0 0.26 11/7
A70360 Full 1.5 0.65 7/1 13/0 0.0 0.67 7/5 2.1 0.67 13/5
Zelandopam Full 4/0 0.0 0.63 40/13 4/0 2.9 0.63 40/2
SKF82958[f] Full 3.8 0.47 22/1 2.2 0.40 50/6 1.8 0.41 22/1 0.0 0.43 50/8
1 Full 1.6 0.59 2/1 1.6 0.61 6/2 0.0 0.22 2/2 0.0 0.13 6/4
2 Full 0.0 0.23 2/2 0.2 0.62 12/6 0.0 0.23 2/2 0.0 0.12 12/6
Dinapsoline Full 0.0 0.39 1/1 0.0 0.45 4/4 0.0 0.39 1/1 0.0 0.45 6/4
Dopamine Full 0.0 0.66 6/1 0.0 0.64 20/8 0.0 0.66 6/1 0.0 0.64 20/8
DHX Full 0.8 0.63 2/1 0.0 0.13 14/14 0.0 0.23 2/1 0.0 0.13 14/8
4[g] Full 0.0 0.55 2/2 0.0 0.56 16/8
4-OH-Dinapsoline[g] Full 0.0 0.36 1/1 0.0 0.46 8/5
6-Et-Dinapsoline[g] Full 0.0 0.37 6/3 0.0 0.46 16/16
A77641 Partial 3/0 11/0 3/0 2.8 0.67 11/2
A70108 Partial 6/0 0.0 0.56 11/7 0.0 0.71 6/3 0.0 0.72 11/7
3 Partial 0.0 0.62 2/2 0.9 0.61 8/4 2/0 8/0
CY-208-243 Partial 3/0 1/0 3/0 1/0
SKF38393 Partial 0.4 0.68 5/2 0.0 0.47 20/16 0.0 0.43 5/3 0.0 0.62 20/10
Apomorphine Partial 0.0 0.61 2/1 0.0 0.62 4/2 0.0 0.61 2/1 0.0 0.62 4/2
(+)-A86929 inactive 10/0 41/0 10/0 49/0
Ro 21-7767[f] Inactive 4/0 8/0 4/0 8/0
cis-DHX Inactive 5/0 12/0 2.7 0.62 5/1 3.4 0.62 12/4
(−)-DHX inactive 0.8 0.74 2/1 8/0 0.8 0.74 2/1 8/0
Rotigotine[f] inactive 1.3 0.73 186/5 1.9 0.72 486/13 3.6 0.69 186/2 486/0
(R)-NPA[f] Inactive 2.5 0.60 6/1 27/0 6/0 27/0
Sumanirole Inactive 5/0 4/0 5/0 4/0
nPr-DHX[f] inactive 1.3 0.42 17/2 3.4 0.43 56/2 17/0 56/0
Quinpirole Inactive 4/0 9/0 4/0 9/0
5 inactive 2/0 8/0
[a]

The energy cutoff for conformations generated in MOE is 4 kcal mol−1.

[b]

The energy cutoff for conformations generated in MacroModel is 16.7 kJ mol−1 (∼4 kcal mol−1).

[c]

The lowest relative energy [kcal mol−1], with respect to the most stable conformer in the ensemble, for the conformers that fit the pharmacophore model.

[d]

Root of the mean square distance between the center of the pharmacophore features and their matching ligand annotation points.

[e]

#c: number of conformations generated for the respective method; #h: number of conformations that hit the pharmacophore model.

[f]

The amine is tertiary and therefore considered chiral, and two different configurations have been used in the modeling.

[g]

The compounds are new in this study and therefore were not screened against the previously published pharmacophore model.