Kloubert S, Mathé-Allainmat M, Andrieux J, Sicsic S, Langlois M
CNRS-BIOCIS (URA 1843), Université de Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
Bioorg Med Chem Lett. 1998 Dec 1;8(23):3325-30. doi: 10.1016/s0960-894x(98)00601-5.
Benzocycloalkane derivatives 1-4 were synthesized as new conformationally restricted melatoninergic ligands. They were prepared by the reaction of the ketones 5 with diethylcyanophosphonate and the reduction of the corresponding cyano compounds or by the Wittig reaction and Curtius degradation to obtain the amines 8. The 1-Cyanobenzocyclobutane derivative was obtained by the benzyne cyclisation reaction. The amines 8 were acylated with acetyl, propionyl or butyryl groups. The affinity of the compounds for chicken brain melatonin receptors was evaluated using 2-[125I]-iodomelatonin as the radioligand. The indanyl (2b,c), tetralin (3a-c) and benzocycloheptane (4c) derivatives were potent compounds with nanomolar affinity and an important enantioselectivity of the receptor was observed with the (+) enantiomers 2b and 3b.
苯并环烷衍生物1-4被合成为新型构象受限的褪黑素能配体。它们通过酮5与氰基磷酸二乙酯的反应以及相应氰基化合物的还原反应制备，或者通过维蒂希反应和库尔提斯降解反应来获得胺8。1-氰基苯并环丁烷衍生物通过苯炔环化反应制得。胺8用乙酰基、丙酰基或丁酰基进行酰化。使用2-[¹²⁵I]-碘褪黑素作为放射性配体评估了这些化合物对鸡脑褪黑素受体的亲和力。茚满基（2b，c）、四氢萘基（3a-c）和苯并环庚烷（4c）衍生物是具有纳摩尔亲和力的强效化合物，并且观察到（+）对映体2b和3b对受体具有重要的对映选择性。
