title: (S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a small molecule inhibitor probe for the study of respiratory syncytial virus infection.
abstract: A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC₅₀ = 2.3 ± 0.8 μM) with marginal cytotoxicity (CC₅₀ = 30.9 ± 1.1 μM) and reduced viral titer by 100-fold. Compared to ribavirin, sulfonylpyrrolidine 5o demonstrated an improved in vitro potency and selectivity index.
authors.affiliation: Southern Research Specialized Biocontainment Screening Center, Southern Research Institute, Birmingham, Alabama 35205, USA.
authors.forename: Blake P
authors.initials: BP
authors.lastname: Moore
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Chung
authors.forename: Daljit S
authors.initials: DS
authors.lastname: Matharu
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Golden
authors.forename: Clinton
authors.initials: C
authors.lastname: Maddox
authors.forename: Lynn
authors.initials: L
authors.lastname: Rasmussen
authors.forename: James W
authors.initials: JW
authors.lastname: Noah
authors.forename: Melinda I
authors.initials: MI
authors.lastname: Sosa
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ananthan
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Tower
authors.forename: E Lucile
authors.initials: EL
authors.lastname: White
authors.forename: Fuli
authors.initials: F
authors.lastname: Jia
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Prisinzano
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
authors.forename: Colleen B
authors.initials: CB
authors.lastname: Jonsson
authors.forename: William E
authors.initials: WE
authors.lastname: Severson
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D057166:High-Throughput Screening Assays; D006801:Humans; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology; D012254:Ribavirin / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019562:Viral Load / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C577925:N-(2,5-dimethylphenyl)-1-(quinolin-8-ylsulfonyl)pyrrolidine-2-carboxamide; D011759:Pyrrolidines; D011804:Quinolines; D013449:Sulfonamides; D013450:Sulfones; D012254:Ribavirin