title: 1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists.
abstract: A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Fabrizio
authors: F
authors: Micheli
authors: Dipartimento di Chimica, Università di Parma , Viale delle Scienze, 17/A, Biopharmanet-tec, Viale delle Scienze, 27/A, Campus, I-43124 Parma, Italy.
authors: Alessia
authors: A
authors: Bacchi
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Simone
authors: S
authors: Braggio
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Laura
authors: L
authors: Castelletti
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Palmina
authors: P
authors: Cavallini
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Paolo
authors: P
authors: Cavanni
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Susanna
authors: S
authors: Cremonesi
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Michele
authors: M
authors: Dal Cin
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Aldo
authors: A
authors: Feriani
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Sylvie
authors: S
authors: Gehanne
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Mahmud
authors: M
authors: Kajbaf
authors: Dipartimento di Chimica, Università di Parma , Viale delle Scienze, 17/A, Biopharmanet-tec, Viale delle Scienze, 27/A, Campus, I-43124 Parma, Italy.
authors: Luciano
authors: L
authors: Marchió
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Selena
authors: S
authors: Nola
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Beatrice
authors: B
authors: Oliosi
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Annalisa
authors: A
authors: Pellacani
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Elisabetta
authors: E
authors: Perdonà
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Anna
authors: A
authors: Sava
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Teresa
authors: T
authors: Semeraro
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Luca
authors: L
authors: Tarsi
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Silvia
authors: S
authors: Tomelleri
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Andrea
authors: A
authors: Wong
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Filippo
authors: F
authors: Visentini
authors: Aptuit s.r.l. , Via Fleming 4, 37135 Verona, Italy.
authors: Laura
authors: L
authors: Zonzini
authors: Indivior Inc. , The Fairfax Building, 10710 Midlothian Turnpike, Suite 430, Richmond Virginia 23235, United States.
authors: Christian
authors: C
authors: Heidbreder
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D018360:Crystallography, X-Ray; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D006536:Heptanes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D006536:Heptanes; D050637:Receptors, Dopamine D3; D013141:Spiro Compounds; D014230:Triazoles