scholarly journals Properties and synthesis of milrinone

2013 ◽  
Vol 67 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Jelena Mirkovic ◽  
Dusan Mijin ◽  
Slobodan Petrovic
Keyword(s):  
Severe Congestive Heart Failure ◽  
Intravenous Therapy ◽  
Alternative Synthesis ◽  
Phosphodiesterase 3 ◽  
Starting Compound ◽  
Cardiotonic Agent ◽  
Oral Form ◽  
Trade Names ◽  
Short Time ◽  
Industry Conditions

Milrinone, 1,6-dihydro-2-methyl-6-oxo-[3,4?-bipyridine]-5-carbonitrile, is a positive inotropic cardiotonic agent with vasodilator properties that acts as selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active than amrinone and possesses reduced propensity to side effects. The use of milrinone has created controversy in the medical as the result of increased mortality rate among patients that received high amounts of milrinone in oral form. Reaserch show that it can be benifitial for patients with severe congestive heart failure when used as short-time intravenous therapy. Milrinone properties, stability, as well as mechanism of action and synthesis under laboratory and industry conditions have been described in this paper. For industrial purposes milrinone is synthesized by condensation of cyanoacetamide with 4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one and 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the reaction of 1-(4-pyridinyl)- 2-propanone with ethoxymethylenmalononitrile or 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of external base. The starting compound for these syntheses is 4-picoline. Alternative synthesis of milrinone starts from 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4-pentadiene-5-carboxamide and 2-methyl-6-oxo-1,6-dihydro-3,4?-bipyridine-5-carboxamide. Lastly, methods for milrinone synthesis in laboratory, injection preparation and purification have been summarized.

scholarly journals Cross metathesis-mediated synthesis of hydroxamic acid derivatives

2018 ◽  
Vol 14 ◽  
pp. 3070-3075 ◽  
Author(s):  
Shital Kumar Chattopadhyay ◽  
Subhankar Ghosh ◽  
Suman Sil
Keyword(s):  
Hydroxamic Acid ◽  
Cyclic Peptide ◽  
Alternative Synthesis ◽  
Acid Component ◽  
Cross Metathesis ◽  
Reaction Proceeds ◽  
Amino Acid Component ◽  
Short Time ◽  
Unusual Amino Acid ◽  
Hydroxamic Acid Derivatives

An alternative synthesis of α,ß-unsaturated hydroxamates via cross metathesis between a class-I olefin and N-benzyloxyacrylamide is reported. The reaction proceeds better in the presence of Grubbs’ second generation catalyst within short time and in good yields (57–85%) with a range of substrates. Subsequent hydrogenation of each of the CM products delivers the title compounds in moderate to very good yield (70–89%). An important demonstration of the protocol is the preparation of the unusual amino acid component of the bioactive cyclic peptide Chap-31.

scholarly journals Efficient Multi-Objective Molecular Optimization in a Continuous Latent Space

2019 ◽  
Author(s):  
Robin Winter ◽  
Floriane Montanari ◽  
Andreas Steffen ◽  
Hans Briem ◽  
Frank Noé ◽  
...  
Keyword(s):  
Objective Function ◽  
In Silico ◽  
Prediction Models ◽  
Chemical Space ◽  
In Silico Prediction ◽  
Swarm Optimization ◽  
Starting Compound ◽  
Latent Space ◽  
Novel Method ◽  
Short Time

In this work, we propose a novel method that combines in silico prediction of molecular properties such as biological activity or pharmacokinetics with an in silico optimization algorithm, namely Particle Swarm Optimization. Our method takes a starting compound as input and proposes new molecules with more desirable (predicted) properties. It navigates a machine-learned continuous representation of a drug-like chemical space guided by a de fined objective function. The objective function combines multiple in silico prediction models, de fined desirability ranges and substructure constraints. We demonstrate that our proposed method is able to consistently fi nd more desirable molecules for the studied tasks in relatively short time.<br>

scholarly journals Efficient Multi-Objective Molecular Optimization in a Continuous Latent Space

2019 ◽  
Author(s):  
Robin Winter ◽  
Floriane Montanari ◽  
Andreas Steffen ◽  
Hans Briem ◽  
Frank Noé ◽  
...  
Keyword(s):  
Objective Function ◽  
In Silico ◽  
Prediction Models ◽  
Chemical Space ◽  
In Silico Prediction ◽  
Swarm Optimization ◽  
Starting Compound ◽  
Latent Space ◽  
Novel Method ◽  
Short Time

In this work, we propose a novel method that combines in silico prediction of molecular properties such as biological activity or pharmacokinetics with an in silico optimization algorithm, namely Particle Swarm Optimization. Our method takes a starting compound as input and proposes new molecules with more desirable (predicted) properties. It navigates a machine-learned continuous representation of a drug-like chemical space guided by a de fined objective function. The objective function combines multiple in silico prediction models, de fined desirability ranges and substructure constraints. We demonstrate that our proposed method is able to consistently fi nd more desirable molecules for the studied tasks in relatively short time.<br>

What the replication reformation wrought

2018 ◽  
Vol 41 ◽  
Author(s):  
Barbara A. Spellman ◽  
Daniel Kahneman
Keyword(s):  
Reform Movement ◽  
Short Time

AbstractReplication failures were among the triggers of a reform movement which, in a very short time, has been enormously useful in raising standards and improving methods. As a result, the massive multilab multi-experiment replication projects have served their purpose and will die out. We describe other types of replications – both friendly and adversarial – that should continue to be beneficial.

Periodic Variations in the Coronal Green Line Intensity and their Connection with the White-light Coronal Structures

2000 ◽  
Vol 179 ◽  
pp. 197-200
Author(s):  
Milan Minarovjech ◽  
Milan Rybanský ◽  
Vojtech Rušin
Keyword(s):  
Time Resolution ◽  
White Light ◽  
Short Time Scale ◽  
High Time Resolution ◽  
Green Line ◽  
Periodic Intensity ◽  
Coronal Green Line ◽  
Significant Intensity ◽  
Short Time ◽  
Coronal Structures

AbstractWe present an analysis of short time-scale intensity variations in the coronal green line as obtained with high time resolution observations. The observed data can be divided into two groups. The first one shows periodic intensity variations with a period of 5 min. the second one does not show any significant intensity variations. We studied the relation between regions of coronal intensity oscillations and the shape of white-light coronal structures. We found that the coronal green-line oscillations occur mainly in regions where open white-light coronal structures are located.

Destruction of Actin Filaments by Osmium Tetroxide

1977 ◽  
Vol 35 ◽  
pp. 466-467
Author(s):  
P. Maupin-Szamier ◽  
T. D. Pollard
Keyword(s):  
Actin Filaments ◽  
Time Course ◽  
Osmium Tetroxide ◽  
Rabbit Muscle ◽  
Muscle Actin ◽  
Sodium Phosphate Buffer ◽  
Transmission Electron ◽  
The Difference ◽  
Rates Of Decay ◽  
Short Time

We have studied the destruction of rabbit muscle actin filaments by osmium tetroxide (OSO4) to develop methods which will preserve the structure of actin filaments during preparation for transmission electron microscopy.Negatively stained F-actin, which appears as smooth, gently curved filaments in control samples (Fig. 1a), acquire an angular, distorted profile and break into progressively shorter pieces after exposure to OSO4 (Fig. 1b,c). We followed the time course of the reaction with viscometry since it is a simple, quantitative method to assess filament integrity. The difference in rates of decay in viscosity of polymerized actin solutions after the addition of four concentrations of OSO4 is illustrated in Fig. 2. Viscometry indicated that the rate of actin filament destruction is also dependent upon temperature, buffer type, buffer concentration, and pH, and requires the continued presence of OSO4. The conditions most favorable to filament preservation are fixation in a low concentration of OSO4 for a short time at 0°C in 100mM sodium phosphate buffer, pH 6.0.

Effect of a Complex Heat Treatment on the Structure of 300M Steel

1981 ◽  
Vol 39 ◽  
pp. 312-313
Author(s):  
R. Padmanabhan ◽  
W. E. Wood
Keyword(s):  
Heat Treatment ◽  
Metal Carbides ◽  
Austenite Grain Size ◽  
300M Steel ◽  
Heat Treated ◽  
Strain Fracture ◽  
Prior Austenite Grain Size ◽  
Short Time ◽  
Final Tempering ◽  
Similar Yield

Intermediate high temperature tempering prior to subsequent reaustenitization has been shown to double the plane strain fracture toughness as compared to conventionally heat treated UHSLA steels, at similar yield strength levels. The precipitation (during tempering) of metal carbides and their subsequent partial redissolution and refinement (during reaustenitization), in addition to the reduction in the prior austenite grain size during the cycling operation have all been suggested to contribute to the observed improvement in the mechanical properties. In this investigation, 300M steel was initially austenitized at 1143°K and then subjected to intermediate tempering at 923°K for 1 hr. before reaustenitizing at 1123°K for a short time and final tempering at 583°K. The changes in the microstructure responsible for the improvement in the properties have been studied and compared with conventionally heat treated steel. Fig. 1 shows interlath films of retained austenite produced during conventionally heat treatment.

Transmission Electron Microscopy of an Aluminum-Silver-Stainless Steel Solid State Bond

1985 ◽  
Vol 43 ◽  
pp. 172-173
Author(s):  
M. J. Carr ◽  
J. F. Shewbridge ◽  
T. O. Wilford
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Solid State ◽  
Specimen Preparation ◽  
Dimensional Control ◽  
Tem Analysis ◽  
Metal Parts ◽  
Dissimilar Metal ◽  
Transmission Electron ◽  
Short Time

Strong solid state bonds are routinely produced between physical vapor deposited (PVD) silver coatings deposited on sputter cleaned surfaces of two dissimilar metal parts. The low temperature (200°C) and short time (10 min) used in the bonding cycle are advantageous from the standpoint of productivity and dimensional control. These conditions unfortunately produce no microstructural changes at or near the interface that are detectable by optical, SEM, or microprobe examination. Microstructural problems arising at these interfaces could therefore easily go undetected by these techniques. TEM analysis has not been previously applied to this problem because of the difficulty in specimen preparation. The purpose of this paper is to describe our technique for preparing specimens from solid state bonds and to present our initial observations of the microstructural details of such bonds.

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