title: Alkylidene Oxapenem β-Lactamase Inhibitors Revisited: Potent Broad Spectrum Activity but New Stability Challenges.
abstract: We present a comprehensive study of C6-alkylidene containing oxapenems. We show that this class of β-lactamase inhibitors possesses an unprecedented spectrum with activity against class A, C, and D enzymes. Surprisingly, this class of compounds displayed significant photolytic instability in addition to the known hydrolytic instability. Quantum mechanical calculations were used to develop models to predict the stability of new analogues.
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Miller
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca India Pvt. Ltd , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kale
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca India Pvt. Ltd , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Kishore
authors.initials: K
authors.lastname: Reddy
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Tentarelli
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Zambrowski
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Minli
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Palmer
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: John
authors.initials: J
authors.lastname: Breen
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Department of Medicinal Chemistry, AstraZeneca India Pvt. Ltd , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Pravin S
authors.initials: PS
authors.lastname: Shirude
authors.affiliation: Infection iMed, AstraZeneca , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Jeroen C
authors.initials: JC
authors.lastname: Verheijen
keywords: Gram-negative infections; Oxapenems; quantum mechanical calculations; stability; β-lactamase inhibitors