Acta Crystallographica Section B

Structural Science

Volume 60, Part 4 (August 2004)

Acta Cryst. (2004). B60, 481-489 [doi:10.1107/S0108768104013564]

Structural features controlling the binding of -carbolines to the benzodiazepine receptor

V. Ferretti, P. Gilli and P. A. Borea

Abstract: [beta] -Carbolines are a class of drug which can interact with a high affinity with the benzodiazepine (BDZ) binding site of the GABA_A receptor. The present paper, aimed at obtaining a deeper insight into the structure-properties relationships of this class of molecules, reports the crystal structures of four [beta] -carbolines: ZK93423 (3-carboethoxy-4-methoxymethyl-6-benzyloxy- [beta] -carboline), ZK91296 (3-carboethoxy-4-methoxymethyl-5-benzyloxy- [beta] -carboline), FG7142 (N-methyl-3-carbamoyl- [beta] -carboline) and the low-affinity ligand harmine hydrochloride (1-methyl-7-methoxy- [beta] -carboline). This set of structural data is completed by the X-ray structures of other carbolines of known biological activity retrieved from the Cambridge Crystallographic Database and by the structures of [beta] -CCE (3-carboethoxy- [beta] -carboline), 6-PBC (3-carboethoxy-4-methoxymethyl-6-isopropoxy- [beta] -carboline), PRCC (3-isopropoxy- [beta] -carboline) and ZK93426 (3-carboethoxy-4-methyl-5-isopropoxy- [beta] -carboline), which have been obtained by molecular-mechanics simulations. The structural features of all these molecules have been compared according to the stereochemical model we proposed in 1987. The structural comparison is integrated by the Free-Wilson analysis on 32 [beta] -carbolines of known binding affinity data.

Online 19 July 2004


	Structure factor file (CIF format) (161.9 kbytes) Contains datablock shelxl

	Structure factor file (CIF format) (157.0 kbytes) Contains datablock shelxl

	Structure factor file (CIF format) (127.5 kbytes) Contains datablock shelxl

	Structure factor file (CIF format) (201.6 kbytes) Contains datablock shelxl

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