| Popis: |
A QSAR and CoMFA study including 78 cocaine analogs has been completed. These analogs have varied functional groups on the 2β and 3β positions of the tropane ring and include various stereoisomers. The CoMFA program was used to calculate the steric and electrostatic interaction energies as a probe atom or probe charge interacts with the molecules. Shaded contour maps show regions of the cocaine analogs where an increase in bulky substituents is desirable for increased pharmacological activity. The maps also show that small electronegative substituents on the phenyl ring are favored for enhanced activity. The X-ray crystal structures of (–)-cocaine hydrochloride (1) and N-methyl-3β-(p-fluorophenyl)tropane-2β-carboxylic acid methyl ester (2) are reported. These molecules are mostly rigid except for some rotational flexibility in the orientation of the phenyl and benzoyl functional groups. Crystallographic data: (1) C17H21NO4·HCl, orthorhombic space group P212121, a = 7.622(1)A, b = 10.285(1)A, c = 21.428(3)A, Z = 4, final R = 0.035 for 960 observed reflections (I>3σ(I)). (2) C16H20FNO2, monoclinic space group C2, a = 22.572(7)A, b = 5.810(1)A, c = 15.752(4)A, β = 133.65(2)°, Z = 4, final R = 0.059 for 1511 observed reflections (I>3σ(I)). |
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