title: Design, synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 receptor (CRF1R).
abstract: Several tetrahydroimidazopyrimidines were prepared using silver assisted cyclization as the key step. The binding affinities of compounds thus prepared were evaluated in vitro toward hCRF(1)R. Initial lead compound 16 (K(i)=32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test. Further optimization using parallel synthesis provided compounds with K(i)'s <50 nM.
authors.affiliation: Bristol-Myers Squibb Research & Development, Wallingford, CT 06492, USA. vivekananda.vrudhula@bms.com
authors.forename: Vivekananda M
authors.initials: VM
authors.lastname: Vrudhula
authors.forename: Bireshwar
authors.initials: B
authors.lastname: Dasgupta
authors.forename: Sokhom S
authors.initials: SS
authors.lastname: Pin
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burris
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Balanda
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Fung
authors.forename: Tracey
authors.initials: T
authors.lastname: Fiedler
authors.forename: Kaitlin E
authors.initials: KE
authors.lastname: Browman
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Taber
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: D000818:Animals; D003500:Cyclization; D015195:Drug Design; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1