Crystal structure of [1-(3-chlorophenyl)- 5-hydroxy-3-methyl-1H-pyrazol-4-yl](p-tolyl) methanone

RK acknowledges the Department of Science & Technology for the single-crystal X-ray diffractometer sanctioned as a National Facility under Project No. SR/S2/CMP-47/2003.Peer reviewe

Evaluation of pyrrolidine and pyrazolone derivatives as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1)

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Tetrahedron Letters 56 (2015): 2832-2835, doi:10.1016/j.tetlet.2015.04.061.Human African trypanosomiasis (HAT) is a parasitic disease, caused by the protozoan pathogen Trypanosoma brucei, which affects thousands every year and which is in need of new therapeutics. Herein we report the synthesis and assessment of a series of pyrrolidine and pyrazolone derivatives of human phosphodiesterase 4 (hPDE4) inhibitors for the assessment of their activity against the trypanosomal phosphodiesterase TbrPDEB1. The synthesized compounds showed weak potency against TbrPDEB1.We acknowledge funding from the National Institutes of Health (R01AI082577)

Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis: Part 2. Synthesis of rigid pyrazolones

Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 μg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity

Chromatography of beer

The objectives of the review are the collection, concise description and evaluation of the various chromatographic techniques used for the separation and quantitative determination of macro- and microcomponents present in beers

Synthesis, biological evaluation and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis

As a continuation of our previous work that turned toward the identification of antimycobacterial compounds with innovative structures, two series of pyrazole derivatives were synthesized by parallel solution-phase synthesis and were assayed as inhibitors of Mycobacterium tuberculosis (MTB), which is the causative agent of tuberculosis. One of these compounds showed high activity against MTB (MIC = 4 μg/mL). The newly synthesized pyrazoles were also computationally investigated to analyze their fit properties to the pharmacophoric model for antitubercular compounds previously built by us and to refine structure–activity relationship analysis

Versatile Synthesis of 4-Methylidenepyrazolidin-3-ones Using a Horner–Wadsworth–Emmons Approach

A new, versatile method for the synthesis of, so far unknown, variously substituted 4-methylidenepyrazolidin-3-ones as potential cytotoxic agents is described. Target compounds were synthesized from the corresponding 4-diethoxyphosphorylpyrazolidin-3-ones which were used as Horner–Wadsworth–Emmons ­reagents for the olefination of formaldehyde. 4-Phosphorylpyrazolidin-3-ones were, in turn, obtained starting from the sodium salt of ethyl 2-diethoxyphosphoryl-3-hydroxy-2-propenoate, ethyl 2-acyl-2-diethoxyphosphorylacetates, or 3-methoxy-2-diethoxyphosphorylacrylate and monosubstituted or 1,2-disubstituted hydrazines

Inhibition of human neutrophil oxidative burst by pyrazolone derivatives

The risk of agranulocytosis associated with the use of pyrazolone drugs at therapeutical doses and for short periods of time has been considered to be very low. However, little or no attention at all has been devoted to the possible hindrance of neutrophil burst and scavenging of neutrophilgenerated reactive oxygen species (ROS) by these compounds. Such an effect could be beneficial in the case of overactivation of neutrophils but could also be highly detrimental if the number of circulating neutrophils is already decreased. Thus, the aim of the present study was to evaluate the putative inhibitory effect of the pyrazolones dipyrone, aminopyrine, isopropylantipyrine, and antipyrine against human neutrophil burst and their scavenging activity against O2 S!, H2O2, HOS, ROOS, and HOCl. The obtained results showed that dipyrone and aminopyrine prevent phorbol-12-myristate-13-acetate-induced neutrophil burst with high efficiency, while isopropylantipyrine had little effect and antipyrine had no effect at all. Dipyrone and aminopyrine were highly potent scavengers of HOS and HOCl, while, in accordance with the neutrophil burst results, isopropylantipyrine had little effect and antipyrine had no effect at all against these two ROS. None of the studied pyrazolones was capable of scavenging O2 S! or H2O2, while dipyrone was shown to be the most reactive against ROOS

Molecular structure elucidation and hydrogen bonding analysis of a pyrazolone derivative

The title compound crystallizes in the monoclinic crystal system with space group P21/c having unit cell parameters: a=7.6329(4), b=7.8137(4), c=28.0651(14) Å, ? =95.995o. The structure converges to a final R-value of 0.0563. The two C-N bonds in Ring B are puckered as the torsion around these bonds is 29.67(2)o and -18.49(2)o , respectively. The two methyl carbons as well as the oxygen atom of the central N-containing five-membered ring (B) are significantly deviated from their mean positions. The magnitude of dihedral angle between the phenyl ring A and B is 133.09(1)o while it is 170.43(1)o between ring B and the phenyl ring C. This indicates that the molecule adopts a non-planar configuration. The crystal structure is stabilized by few C-H…O and C-H…N inter and intramolecular hydrogen interactions

The Significance of the Adrenal Medullary Epinephrin in the Analgesic Effects of Morphine and a Few Other Drugs in Mice

The analgesic effects of morphine and some related compounds, such as meperidine, observed by the conventional method, are supplemented by the release of epinephrine from the adrenal medulla. It is assumed that this action of epinephrine is not due to an additive synergy in the analgesic effect but to the face that the action of epinephrine on a definite higher center or centers effects synergistically in the reflex depressant action of these analgesic agants. This assumption is based on the following evidences. Prolongation of reaction time in mice by morphine and meperidine (but not by ohton), determined by the hot-plate method, was significantly reduced by adrenalectomy and this reduction was normalized by the concurrent use of epinephrine, in a small dose which in itself cannot prolong the reaction time. No such action was found in cortisone and DOCA. The effects of morphine and meperidine in prolonging the reaction time were reduced by priscol and dibenamine, as well as by tetraethylammonium salt. A large dose of pyrazolone derivatives causes, not the prolongation of reaction time but a jumping reflex response in the early stages, indicating central excitation, in part of the mice. The ratio of mice exhibiting such an early reflex increases with adrenalectomy or the administration of dibenamine, and is markedly decreased by epinephrine, insufficient to show any analgesic response by itself, and by cortisone. This action of cortisone indicates some difference in the natures of central excitation by pyrazolones and by morphine. Judging from the work of SCHAYER18, the distribution in the brain of epinephrine injected in the dose to normalize the reduced effect of morphine in the adrenalectomized mice, may also be anticipated by the epinephrine which might be released from the adrenal medulla by morphine in an amount much smaller than the &#34;near·lethal doses9 &#34;.</p