The elusive crystal structure of the neuraminidase inhibitor Tamiflu (oseltamivir phosphate): molecular details of action

2013 ◽  
Vol 49 (19) ◽  
pp. 1948 ◽  
Author(s):  
Panče Naumov ◽  
Nobuhiro Yasuda ◽  
Wael M. Rabeh ◽  
Joel Bernstein
Keyword(s):  
Crystal Structure ◽  
Neuraminidase Inhibitor ◽  
Oseltamivir Phosphate

The Synthetic Development of the Antiinfluenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu): A Challenge for Synthesis & Process Research

ChemInform ◽  
2005 ◽  
Vol 36 (30) ◽  
Author(s):  
Stefan Abrecht ◽  
Peter Harrington ◽  
Hans Iding ◽  
Martin Karpf ◽  
Rene Trussardi ◽  
...  
Keyword(s):  
Neuraminidase Inhibitor ◽  
Process Research ◽  
Synthesis Process ◽  
Oseltamivir Phosphate

scholarly journals Crystal Structure of the Trihydrate of the Neuraminidase Inhibitor C15H28N4O4 (Peramivir), a Potential Influenza A/B and Avian-influenza (H5N1) Drug

2007 ◽  
Vol 62 (8) ◽  
pp. 983-987 ◽  
Author(s):  
Egbert Keller ◽  
Volker Krämer
Keyword(s):  
Crystal Structure ◽  
Avian Influenza ◽  
Influenza A ◽  
Organic Molecules ◽  
Neuraminidase Inhibitor ◽  
X Rays ◽  
Water Layers ◽  
Long Time ◽  
Influenza H5n1 ◽  
Water Contents

The crystal structure of the trihydrate of peramivir (C15H28N4O4), a potential influenza A/B and avian-influenza drug, has been determined. The structure, belonging to the tetragonal space group P42212 with Z = 32, a = 27.216(4), c = 23.084(5) Å, V = 17098(5) Å3, contains four organic molecules plus 12 partially disordered water molecules per asymmetric unit. 16 Organic molecules per unit cell form a kind of 1D infinite micelle separated from vicinal micelles by approximately planar water layers. During exposure to X-rays or under long-time storage on air peramivir trihydrate undergoes a phase transition to a structurally closely related phase with reduced water contents.

scholarly journals Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate Induces Canine Mammary Cancer Cell Aggressiveness

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0121590 ◽  
Author(s):  
Joana T. de Oliveira ◽  
Ana L. Santos ◽  
Catarina Gomes ◽  
Rita Barros ◽  
Cláudia Ribeiro ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Mammary Cancer ◽  
Neuraminidase Inhibitor ◽  
Mammary Cancer Cell ◽  
Canine Mammary Cancer ◽  
Oseltamivir Phosphate

scholarly journals Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; a phase 2, multicenter, double-blind, randomized trial

2022 ◽  
Vol 16 (1) ◽  
pp. e0010051
Author(s):  
Rahajeng N. Tunjungputri ◽  
Silvita Fitri Riswari ◽  
Setyo G. Pramudo ◽  
Lydia Kuntjoro ◽  
Bachti Alisjahbana ◽  
...  
Keyword(s):  
Platelet Count ◽  
Randomized Trial ◽  
Neuraminidase Inhibitor ◽  
Phase 2 ◽  
Double Blind ◽  
Platelet Recovery ◽  
Duration Of Illness ◽  
Plasma Leakage ◽  
Discharge From Hospital ◽  
Oseltamivir Phosphate

Background Thrombocytopenia, bleeding and plasma leakage are major complications of dengue. Activation of endogenous sialidases with desialylation of platelets and endothelial cells may underlie these complications. We aimed to assess the effects of the neuraminidase inhibitor oseltamivir on platelet recovery and plasma leakage in dengue. Methods We performed a phase 2, double-blind, multicenter, randomized trial in adult dengue patients with thrombocytopenia (<70,000/μl) and a duration of illness ≤ 6 days. Oseltamivir phosphate 75mg BID or placebo were given for a maximum of five days. Primary outcomes were the time to platelet recovery (≥ 100,000/μl) or discharge from hospital and the course of measures of plasma leakage. Results A total of 70 patients were enrolled; the primary outcome could be assessed in 64 patients (31 oseltamivir; 33 placebo). Time to platelet count ≥100,000/μl (n = 55) or discharge (n = 9) were similar in the oseltamivir and placebo group (3.0 days [95% confidence interval, 2.7 to 3.3] vs. 2.9 days [2.5 to 3.3], P = 0.055). The kinetics of platelet count and parameters of plasma leakage (gall bladder thickness, hematocrit, plasma albumin, syndecan-1) were also similar between the groups. Discussion In this trial, adjunctive therapy with oseltamivir phosphate had no effect on platelet recovery or plasma leakage parameters. Trial registration ISRCTN35227717.

scholarly journals Laninamivir Prodrug CS-8958, a Long-Acting Neuraminidase Inhibitor, Shows Superior Anti-Influenza Virus Activity after a Single Administration

2010 ◽  
Vol 54 (3) ◽  
pp. 1256-1264 ◽  
Author(s):  
Shuku Kubo ◽  
Takanori Tomozawa ◽  
Masayo Kakuta ◽  
Akane Tokumitsu ◽  
Makoto Yamashita
Keyword(s):  
Influenza Virus ◽  
Influenza Virus Infection ◽  
Neuraminidase Inhibitor ◽  
Infection Model ◽  
Single Administration ◽  
Mouse Infection Model ◽  
Significant Efficacy ◽  
Long Acting ◽  
Oseltamivir Phosphate

ABSTRACT Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate (Tamiflu), have been licensed for use for the treatment and prophylaxis of influenza. We have reported on laninamivir (code name, R-125489), a novel neuraminidase inhibitor, and have discovered that the laninamivir prodrug CS-8958 worked as a long-acting neuraminidase inhibitor in a mouse influenza virus infection model when it is intranasally administered. In this study, CS-8958 was administered just once 7 days before infection and showed significant efficacy in vivo. The efficacy of a single administration of CS-8958 after viral infection was then compared with that of repeated administrations of oseltamivir phosphate or zanamivir in mice and ferrets. CS-8958 showed efficacy superior or similar to the efficacies of the two licensed NA inhibitors. CS-8958 also significantly reduced the titers of an oseltamivir-resistant H1N1 virus with a neuraminidase H274Y substitution in a mouse infection model. These results suggest that since CS-8958 is characteristically long lasting in the lungs, it may be ideal for the prophylaxis and treatment of influenza.

Powder X-ray diffraction of oseltamivir phosphate (Tamiflu®), C16H31N2O8P

2020 ◽  
Vol 35 (3) ◽  
pp. 216-218
Author(s):  
Ryan L. Hodge ◽  
James A. Kaduk ◽  
Amy M. Gindhart ◽  
Thomas N. Blanton
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Powder Diffraction ◽  
Density Functional ◽  
Van Der Waals Interactions ◽  
X Ray Diffraction ◽  
Powder Diffraction File ◽  
X Ray ◽  
Oseltamivir Phosphate ◽  
Phosphate Groups

The crystal structure of oseltamivir phosphate has been refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Oseltamivir phosphate crystallizes in space group P21212 (#18) with a = 24.0079(3), b = 24.6716(2), c = 7.45254(5) Å, V = 4414.24(5) Å3 at 295 K, and Z = 8. Prominent in the crystal structure are hydrogen bonds between the phosphate groups and the ammonium groups of the oseltamivir cations. The strong hydrogen bonds link the cations and the anions into columns parallel to the c-axis, with van der Waals interactions between the columns. Thermal expansion between 120 and 295 K is anisotropic. The powder pattern is included in the Powder Diffraction File™ as entry 00-068-1107.

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