title: Discovery of a potent, selective and orally bioavailable 3,9-diazaspiro[5.5]undeca-2-one CCR5 antagonist.
abstract: Replacement of the cyclic carbamate in our previously disclosed 1-oxa-3,9-diazaspiro[5.5]undecan-2-one template led to the discovery of two novel series of 3,9-diazaspiro[5.5]undecane and undeca-2-one CCR5 antagonists. The synthesis, SAR, and antiviral activities of these two series are described. One compound (32) was found to have attractive combination of antiviral potency, selectivity, and pharmacokinetic profile. The asymmetric synthesis of 32 was also accomplished and both enantiomers were equally potent.
authors.affiliation: Roche Palo Alto LLC, Palo Alto, CA 94304, USA. hanbiaoyang@gmail.com
authors.forename: Hanbiao
authors.initials: H
authors.lastname: Yang
authors.forename: Xiao-Fa
authors.initials: XF
authors.lastname: Lin
authors.forename: Fernando
authors.initials: F
authors.lastname: Padilla
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gabriel
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Heilek
authors.forename: Changhua
authors.initials: C
authors.lastname: Ji
authors.forename: Surya
authors.initials: S
authors.lastname: Sankuratri
authors.forename: André
authors.initials: A
authors.lastname: deRosier
authors.forename: Pamela
authors.initials: P
authors.lastname: Berry
authors.forename: David M
authors.initials: DM
authors.lastname: Rotstein
mesh_terms: D000284:Administration, Oral; D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D065100:CCR5 Receptor Antagonists; D055808:Drug Discovery; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D000998:Antiviral Agents; D065100:CCR5 Receptor Antagonists; D013141:Spiro Compounds; C022884:undecane