Wet granulation is one of the fundamental
unit operations for manufacturing pharmaceutical solid dosage forms including
tablets. This study investigated in detail the states of water incorporated in
wet granules composed of different fillers. The key instrument to evaluate the
state of water was a low-field benchtop 1H-NMR time-domain NMR
(TD-NMR). This study successfully concluded that the state of water
significantly affected the wet granulation process and the characteristics of
the resultant granules. The findings can offer valuable knowledge on wet
granulation process from the viewpoint of molecular mobility of water.
A number of clinical trials demonstrated that
tigecycline was effective and well tolerated in the treatment of patients with
various bacterial infections, but few literatures had shown the coagulopathy
induced by tigecycline. The retrospective analysis in this paper to assess the impact of tigecycline on
coagulation parameters in 50 patients showed that the plasma fibrinogen (FIB)
level decreased during treatment, which was statistically significant (P < 0.001). The mean values of
activated partial thromboplastin time (aPTT) and prothrombin time (PT) were
significantly increased, respectively. It is
necessary for practitioners routinely monitor coagulation level in at-rick
patient populations treated with tigecycline.
When a neutral solution of a nucleoside
mixture was irradiated with UV light having wavelength longer than 300 nm,
addition of salicylic acid to the solution greatly accelerated the reaction of
thymidine. The UV light irradiation of thymidine solution in the presence of
salicylic acid generated isomers of cyclobutane thymidine dimers almost
exclusively. UV irradiation with the longer wavelength of 350 nm induced almost
no reaction. The results indicate that salicylic acid is a photosensitizer for
thymidine dimerization excited by UV light of wavelength 300 to 350 nm.
“Chocolet” is an orally disintegrating tablet formulated with cocoa powder to
mask the bitterness of drugs. The name “Chocolet” indicates that the
formulation combines the good taste of chocolate
with the ease of taking of an orally disintegrating tablet. Rebamipide chocolet has been prepared with excellent
palatability properties, which could not be achieved using a sweetener alone,
by using the combination of a sweetener and cocoa powder as an agent for
masking bitterness. “Chocolet” can be used to provide patient-friendly tablets, thus helping to improve medication adherence.
Isoschizogamine is a member of the schizozygane family of indole
alkaloids. Its highly fused hexacyclic structure containing an aminal adjacent
to a quaternary stereocenter makes it a challenging synthetic target. While the authors reported the total synthesis of
(–)-isoschizogamine in 2012, this paper describes an alternative preparation of
their pivotal synthetic intermediate. The synthesis features a stereoselective
construction of a quaternary carbon by the Claisen-Johnson rearrangement and a
stereoselective rhodium-mediated 1,4-addition of arylboronic acid. The
reliability of this synthetic route enables a
sufficient supply of the intermediate for the total synthesis of isoschizogamine.
of repeatability in supercritical fluid chromatography with electrochemical
detection (SFC-ECD) system is necessary to construct an SFC-ECD as a
quantitative method with satisfactory precision. This article is the first report that a
method for the assessment of repeatability in SFC-ECD has been proposed by
means of the ISO 11843 part 7 which can theoretically provide detection limits
and standard deviation (SD) through the stochastic properties of baseline noise
without repetitive measurements of real samples. The present method is practically useful,
and both experimental time and chemicals can be saved to estimate the
repeatability in SFC-ECD.
A series of 8-methoxy or
8-methylquinolones bearing novel 3-aminooctahydrocyclopenta[c]pyrrole
derivatives at the C-7 position was synthesized, and the pharmacological,
physicochemical, and toxicological properties of the individual compounds were
evaluated. Novel 7-[(1R,5S)-1-amino-5-fluoro-3-azabicyclo[3.3.0]octan-3-yl]-6-fluoro-8-methylquinolone
7 exhibited potent and better activity than
LVFX and MFLX against streptococci, staphylococci, enterococci, E. coli, A. baumannii, and anaerobes. Compound 7 also demonstrated favorable
pharmacokinetic and pharmacodynamic properties and an acceptably safe
toxicological profile. Consequently, compound 7 was selected as a clinical candidate for further evaluation as a new-generation,
broad-spectrum quinolone antibiotic. Compound 7 is expected to become an option for antibacterial therapy against multidrug-resistant A.
Polygenetic and complex diseases are great burden
and challenge of human, such as ischemic cerebrovascular disease (ICD) and
cardiovascular diseases (CVD). Drug repositioning, is one important approach to
reexamine the new indications of marketed drugs, especially drugs with
multi-targets. Based on the interplay among diseases, genes (targets) and
drugs, new method can be applied to dissect the association information. A
multi-database, in silico target identification, gene function enrichment, and
network pharmacology analysis integrated methods were proposed to investigate
the approved CVD drugs repurposing for ICD. It provides promising alternative
to inferring novel disease indications for existing safe and effective drugs.
Oxiranyl anions are very unstable and uncommon
nucleophiles while epoxies are widely used as electrophiles in organic chemistry.
A sulfonyl-stabilized oxiranyl anion reacts efficiently with a triflate to afford
an alkylated product in high yield. The high synthetic potential of the
oxiranyl anion chemistry was demonstrated by the total synthesis of gymnocin-A,
a cytotoxic polycyclic ether marine natural product produced by the red tide
organism Karenia mikimotoi.
This paper describes a short total
synthesis of (+)-spinoxazine B, which inhibits NO production in BV-2 microgrial
cells. The synthesis features a double cyclization to rapidly construct the
bicyclic skeleton of spinoxazine B. Spinoxazine B is the first example of a
natural alkaloid containing an oxazinone-pyrrolidone nucleus. Because new ring
system is considered to be a new resource for drug discovery, spinoxazine B is
expected to serve as a novel drug lead compound as well as a drug discovery
A TLC-based simple and convenient
method using UV-sensitive constituents as markers to identify the crude drug Polygala
Root (the root of Polygala tenuifolia
Willdenow; Japanese name “Onji”) was investigated. Twenty-three aromatic
compounds including two new compounds, polygalaonjisides A and B, were
characterized. Based on the phytochemical results obtained, a TLC method
focusing on three marker spots with Rf
values of approximately 0.4-0.5 due to tenuifolisides A and B
and 3,6′-di-O-sinapoylsucrose was proposed as a
simple and convenient test to identify Polygala Root and its single-extract
products on the market. The data presented in this paper could be useful in
stipulating a confirmation test to identify Polygala Root.
Continuous flow synthesis has drawn increasing attention
in current organic synthesis. In this paper, the authors demonstrate a new
entry for the beneficial application of a microflow reactor to the synthesis of
aromatic fluorinated compounds via domino benzyne generation/nucleophilic
fluorination. In particular, the high mixing ability of the flow reactor significantly
reduced the reaction times to ~10 s and improved the product yields in comparison
to their previously reported method under ordinary batch conditions. In some
cases, aryl fluorides were obtained only under microflow conditions. Thus, the
flow chemistry is the method not only for continuous chemical production but
also for achieving transformations that are otherwise inaccessible by the
conventional batch method.
novel series of pentacoordinated organotin(IV) complexes derived from L-DOPA
were designed; the synthesis was performed by a one-pot strategy. The
biological evaluation revealed that organotin complexes were substantially more cytotoxic than cisplatin and significantly more
effective than Topotecan in inhibiting the growth of leukemia, breast and lung
cancer cell lines. The
cytotoxicity depended on the nature of the substituent bonded to the aromatic
ring. The brine shrimp lethality assay was also used to determine the toxicity.
Molecular docking revealed that organotin (IV) complexes bind to the active
site of topoisomerase I. Antifungal activity was tested against species of
The i-motif is a high-order DNA structure,
forming in cytosine-rich sequences of gene promoters and telomeric regions. Due
to the limited stability of this structure under the physiological conditions,
the i-motif DNA was unknown for several years. Recently, the biological
functions of this DNA and its application have been discovered by applying
i-motif interacting agents which is showing the importance of these ligands in
uncovering the distinctive features of i-motif.
Quercetin-pivaloxymethyl conjugate (Q-POM) potentiated the activity of ampicillin, cefepime, and vancomycin against S. aureus and Enterococcus (including highly resistant strains such as hVISA, VISA, and VRE), by decreasing the MICs of these antibiotics by 4-128 folds. Q-POM was found to be partially synergistic with ampicillin and cefepime against S. aureus and Enterococcus, while it was strongly synergistic with vancomycin. Q-POM at 5 mg/L inhibited the formation of biofilms of S. aureus by 24-83% and VRE by 70%. Additionally, Q-POM inhibited the hemolytic activity of S. aureus in a dose-dependent manner.
Metal carbenoid species are known to insert into a C−H bond, C=X double bonds (X = C, N, O), and Y−H bonds (Y = N, O, Si, P, S, etc), however, a carbenoid insertion into a urea C−N bond has not yet been reported. In the article, the first urea insertion reaction of carbenoid species is described. The urea insertion reaction proceeded smoothly using Rh2(NHPiv)4, a rhodium catalyst previously designed by the authors’ group, to produce highly functionalized bridged molecules with three adjacent stereocenters.
Primary drying conditions for the commercial manufacturing were designed based on the vial heat transfer coefficient of the production lyophilizer and the drying resistance (Rp) calculated from manufacture with the pilot lyophilizer under dust-free condition. The production scale-verification study confirmed that the Rp obtained using pilot lyophilizer under dust-free condition could be available for the production lyophilizer. This scale-up theory, which bridges the gap between the laboratory scale and the production scale, is useful for the development of an efficient and robust process at production scale.
For organic synthesis in the field of pharmaceutical sciences, methodologies that can easily and quickly supply compounds with high drug-likeness is highly desirable. Based on the original catalyst design concept "Radical-Conjugated Redox Catalysis (RCRC)" established during author's research, various C(sp3)-H functionalizations and protein modifications have been developed, taking advantage of high reactivity and chemoselectivity of single-electron transfer process. This review will focus on the research concept and efforts over eight years of the author and his collaborators.
Allylic fluoride is a useful synthetic intermediate for the preparation of various organofluorine compounds. The authors demonstrated a highly enantioselective fluorination of cyclic tetrasubstituted alkenes with a pendant amide group using their dianionic phase-transfer catalyst. The deprotonative fluorination mainly proceeded in preference to the intramolecular nucleophilic attack of the amide group, and the corresponding allylic fluorides with a chiral tetrasubstituted carbon center were obtained with up to 97% ee.
The amlodipine dissolution from orally disintegrating tablets (ODTs) in vivo in the human oral cavity was examined. Various amlodipine ODTs with different levels of physical masking effectiveness were manufactured. The present results are the first to show that drug dissolution from ODT is dependent on time in the oral cavity and coating amount. The mimicking of the inside of the human oral cavity is accurate with a testing time of 30 s, while the Tricorptester method was the most preferable of all in vitro short dissolution test methods investigated in this study.