Novel 5-HT7 Receptor Inverse Agonists. Synthesis and Molecular Modeling of Arylpiperazine- and 1,2,3,4-Tetrahydroisoquinoline-Based Arylsulfonamides

التفاصيل البيبلوغرافية
العنوان:	Novel 5-HT7 Receptor Inverse Agonists. Synthesis and Molecular Modeling of Arylpiperazine- and 1,2,3,4-Tetrahydroisoquinoline-Based Arylsulfonamides
المؤلفون:	Vermeulen, E. S., Smeden, M. van, Schmidt, A. W., Sprouse, J. S., Wikstrom, H. V., Grol, C. J.
المصدر:	Journal of Medicinal Chemistry; October 2004, Vol. 47 Issue: 22 p5451-5466, 16p
مستخلص:	A series of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides was synthesized and evaluated for their interactions with the constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced a decrease of adenylate cyclase activity, indicative of their inverse agonism. Additionally, computational studies with a set of 22 inverse agonists, including these novel inverse agonists and inverse agonists known from literature, resulted in a pharmacophore model and a CoMFA model (R² = 0.97, SE = 0.18). Docking of inverse agonists at the binding site of a model of the helical parts of the 5-HT7 receptor, based on the α carbon template for 7-TM GPCRs, revealed interesting molecular interactions and a possible explanation for observed structure−activity relationships.
قاعدة البيانات:	Supplemental Index

الوصف
تدمد:	00222623 15204804