Orally Active Non-Peptide Fibrinogen Receptor (GpIIb/IIIa) Antagonists: Identification of 4-[4-[4-(Aminoimino methyl)phenyl]-1-piperazinyl]-1- piperidineacetic Acid as a Long-Acting, Broad-Spectrum Antithrombotic Agent

1994 ◽  
Vol 37 (23) ◽  
pp. 3882-3885 ◽  
Author(s):  
Colin D. Eldred ◽  
Brian Evans ◽  
Sean Hindley ◽  
Brian D. Judkins ◽  
Henry A. Kelly ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antithrombotic Agent ◽  
Fibrinogen Receptor ◽  
Long Acting ◽  
Orally Active ◽  
Methyl Phenyl

Non-Peptide Glycoprotein IIb/IIIa Inhibitors. 17. Design and Synthesis of Orally Active, Long-Acting Non-Peptide Fibrinogen Receptor Antagonists

1997 ◽  
Vol 40 (12) ◽  
pp. 1779-1788 ◽  
Author(s):  
Benny C. Askew ◽  
Rodney A. Bednar ◽  
Bohumil Bednar ◽  
David A. Claremon ◽  
Jacquelynn J. Cook ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Design And Synthesis ◽  
Fibrinogen Receptor ◽  
Long Acting ◽  
Orally Active

Highly stereoselective access to novel 2,2,4-substituted tetrahydrofurans by halocyclization: Practical chemoenzymatic synthesis of Sch 51048, a broad-spectrum orally active antifungal agent

1995 ◽  
Vol 36 (11) ◽  
pp. 1787-1790 ◽  
Author(s):  
Anil K Saksena ◽  
Viyyoor M Girijavallabhan ◽  
Raymond G Lovey ◽  
Russell E Pike ◽  
Haiyan Wang ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antifungal Agent ◽  
Chemoenzymatic Synthesis ◽  
Orally Active

Comparative Studies of an Orally-active Factor Xa Inhibitor, YM-60828, with other Antithrombotic Agents in a Rat Model of Arterial Thrombosis

1998 ◽  
Vol 79 (02) ◽  
pp. 410-416 ◽  
Author(s):  
Kazuo Sato ◽  
Yumiko Sakai ◽  
Fukushi Hirayama ◽  
Hiroyuki Koshio ◽  
Yuta Taniuchi ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Test Drug ◽  
Antithrombotic Agent ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Treatment And Prevention ◽  
Orally Active

SummaryWe examined the antithrombotic activity of a novel synthetic inhibitor of factor Xa, YM-60828, in an electrically-induced carotid artery thrombosis model in rats. In the first experiment, the antithrombotic activity of YM-60828 after i.v. infusion was compared with those of heparin, darteparin and argatroban. Test drug was administered by i.v. infusion from 30 min before electrical stimulation to the end of the experiment. YM-60828 at 1 mg/kg/h significantly improved patency status, prolonged the time to occlusive thrombus formation and duration of patency. Heparin at 300 U/kg/h also improved these parameters, but were accompanied by a marked increase in systemic coagulation time. In the second experiment, the antithrombotic activity of YM-60828 after oral administration was compared with those of ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate and warfarin. Test drug was orally administered to fasted rats 60 min before electrical stimulation. YM-60828 at 30 mg/kg p.o., but not ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate or warfarin, significantly reduced the incidence of occlusion and improved carotid arterial patency. These results suggest that YM-60828 may be a promising antithrombotic agent for the treatment and prevention of arterial thrombosis which can be given by oral as well as intravenous administration.

scholarly journals Chemical Polysialylation and In Vivo Tetramerization Improve Pharmacokinetic Characteristics of Recombinant Human Butyrylcholinesterase-Based Bioscavengers

Acta Naturae ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 136-141 ◽  
Author(s):  
S. S. Terekhov ◽  
I. V. Smirnov ◽  
O. G. Shamborant ◽  
T. V. Bobik ◽  
D. G. Ilyushin ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Large Scale ◽  
Promising Candidate ◽  
Protective Index ◽  
Polysialic Acids ◽  
Long Acting ◽  
Nerve System ◽  
Molecular Compounds ◽  
Human Butyrylcholinesterase

Organophosphate toxins (OPs) are the most toxic low-molecular compounds. The extremely potent toxicity of OPs is determined by their specificity toward the nerve system. Human butyrylcholinesterase (hBChE) is a natural bioscavenger against a broad spectrum of OPs, which makes it a promising candidate for the development of DNA-encoded bioscavengers. The high values of the protective index observed for recombinant hBChE (rhBChE) make it appropriate for therapy against OP poisoning, especially in the case of highly toxic warfare nerve agents. Nevertheless, large-scale application of biopharmaceuticals based on hBChE is restricted due to its high cost and extremely rapid elimination from the bloodstream. In the present study, we examine two approaches for long-acting rhBChE production: I) chemical polysialylation and II) in-vivo tetramerization. We demonstrate that both approaches significantly improve the pharmacokinetic characteristics of rhBChE (more than 5 and 10 times, respectively), which makes it possible to use rhBChE conjugated with polysialic acids (rhBChE-CAO) and tetrameric rhBChE (4rhBChE) in the treatment of OP poisonings.

Discovery of an Orally Active and Long‐Acting DPP‐IV Inhibitor through Property‐Based Optimization with an in Silico Biotransformation Prediction Tool

ChemMedChem ◽  
2020 ◽  
Vol 15 (16) ◽  
pp. 1608-1617
Author(s):  
Shaogao Zeng ◽  
Wenyuan Dou ◽  
Manna Li ◽  
Yang Zhou ◽  
Jiehuang Guo ◽  
...  
Keyword(s):  
In Silico ◽  
Prediction Tool ◽  
Dpp Iv ◽  
Long Acting ◽  
Orally Active

Design of a New Class of Orally Active Fibrinogen Receptor Antagonists

1998 ◽  
Vol 41 (14) ◽  
pp. 2492-2502 ◽  
Author(s):  
Scott I. Klein ◽  
Bruce F. Molino ◽  
Mark Czekaj ◽  
Charles J. Gardner ◽  
Valeria Chu ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
New Class ◽  
Fibrinogen Receptor ◽  
Orally Active
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