title: Novel tetrahydropyrido[3,2-c]pyrroles as 5-HT(7) antagonists.
abstract: The synthesis and SAR for a novel series of tetrahydropyrido[3,2-c]pyrroles is described. Optimization of the pendant aryl ring lead to high binding affinity at the 5-HT(7) receptor when small lipophilic groups were placed in the para position. Modification of the N-benzyl group and secondary amine were not well tolerated. A representative set of compounds was shown to be functional antagonists of the 5-HT(7) receptor.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States. drudolph@its.jnj.com
authors.forename: Dale A
authors.initials: DA
authors.lastname: Rudolph
authors.forename: Curt A
authors.initials: CA
authors.lastname: Dvorak
authors.forename: Lisa
authors.initials: L
authors.lastname: Dvorak
authors.forename: Diane
authors.initials: D
authors.lastname: Nepomuceno
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonaventure
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
mesh_terms: D000818:Animals; D011485:Protein Binding; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D011758:Pyrroles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor