Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo.
Cyclopentane derivatives, designated as BCX-1812, BCX-1827, BCX-1898, and BCX-1923, were tested in parallel with oseltamivir carboxylate and zanamivir for the in vivo activity in mice infected with A/Turkey/Mas/76 X A/Beijing/32/92 (H6N2) influenza virus. The compounds were tested orally and intranasally at different dose levels. BCX-1812, BCX-1827, and BCX-1923 showed more than 50% protection at 1mg/kg/day dose level on oral treatment. The intranasal treatment was 100% effective even at 0.01 mg/kg/day for all four compounds. On comparison with oseltamivir carboxylate and zanamivir, these four cyclopentane derivatives have shown equal or better efficacies. The synthesis of two new compounds, BCX-1898 and BCX-1923, is also described.
Chand
Pooran
P
BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA. pchand@biocryst.com
Bantia
Shanta
S
Kotian
Pravin L
PL
El-Kattan
Yahya
Y
Lin
Tsu-Hsing
TH
Babu
Yarlagadda S
YS
D000081:Acetamides / Q000494:pharmacology; D000146:Acids, Carbocyclic; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D003517:Cyclopentanes / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines; D051379:Mice; D009975:Orthomyxoviridae / Q000187:drug effects*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D053139:Oseltamivir; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015996:Survival Rate; D016896:Treatment Outcome; D053243:Zanamivir
D000081:Acetamides; D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D053243:Zanamivir; C414210:peramivir