Pyrazole Moiety Research Articles

Disulfide linked pyrazole derivatives inhibit phagocytosis of opsonized blood cells

Immune thrombocytopenia (ITP) is caused by production of an autoantibody to autologous platelets. ITP can be treated either by reducing platelet destruction or by increasing platelet production. Fcγ receptor mediated phagocytosis of the opsonized blood cells is a well-accepted mechanism for the underlying pathogenesis of ITP and inhibition of this phagocytosis process with small molecules is a potential strategy for the development of drugs against ITP. A broad screen indicated that 4-methyl-1-phenyl-pyrazole derivative (1) could inhibit the phagocytosis of opsonized blood cells with weak potency. We reveal here the discovery of the polysulfide products, synthesis of various 1-phenyl-pyrazole derivatives, and the biological evaluation of pyrazole derivatives as inhibitors of phagocytosis for potential use as therapeutics for ITP. Substitution at C4 of the pyrazole moiety in the disulfide-bridged dimers influenced the potency in the increasing order of 10≅11≅16<19<20. A novel scaffold, 20 with an IC50 of 100nM inhibiting opsonized blood cell phagocytosis was identified as a potential candidate for further studies. Confirmation of the disulfide bridge additionally provides clues for the non-thiol or non-disulfide bridge carrying ligands targeting ITP and other similar disorders.

ChemInform Abstract: Efficient and Rapid Synthesis of Highly Functionalized Novel Symmetric 1,4‐Dihydropyridines Using Glacial Acetic Acid as Solvent.

AbstractNovel 1,4‐dihydropyridines (III) (14 examples) bearing a pyrazole moiety in 4‐position are prepared by a variation of the classical Hantzsch synthesis.

Synthesis and biological evaluation of modified purine homo-N-nucleosides containing pyrazole or 2-pyrazoline moiety

9-Substituted (pyrazol-5-yl)methyl- or (2-pyrazolin-5-yl)methyl-9H-purines were synthesized from 9-allyl-6-chloro-9H-purine through the 1,3-dipolar cycloaddition reaction with nitrile imines, prepared in situ from the corresponding hydrazone and NBS/Et3N under MW or from hydrazinoylchloride and Et3N under reflux. The coupling of new 6-chloropurines with amines in H2O under microwaves resulted quantitatively to modified pyrazol-5-yl- or 2-pyrazolin-5-yl adenine homo-N-nucleosides. The new compounds were tested in vitro for their ability to: (i) interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH), (ii) inhibit lipid peroxidation, (iii) inhibit the activity of soybean lipoxygenase, (iv) inhibit in vitro thrombin and for (v) their antiproliferative and cytotoxic activity. Pyrazolines were found to be more potent in vitro. Compound 7a exhibited satisfactory combined antioxidant and anti-lipid peroxidation activity, inhibition of lipoxygenase (89%) and thrombin inhibitory ability, whereas compound 7b exhibited high lipoxygenase inhibitory activity in combination to significant anti-thrombin activity. No compound exhibited a significant cytotoxic activity, while all showed moderate antiproliferative activity.

ChemInform Abstract: Dapson in Heterocyclic Chemistry. Part 5. Synthesis, Molecular Docking and Anticancer Activity of Some Novel Sulfonylbiscompounds Carrying Biologically Active Dihydropyridine, Dihydroisoquinoline, 1,3‐Dithiolan, 1,3‐Dithian, Acrylamide, Pyrazole, Pyrazolopyrimidine and Benzochromene Moieties.

AbstractAll the synthesized compounds, especially the benzochromene derivatives, show better cytotoxic activity than the reference drug doxorubicin.

Dimerized Spin‐Crossover Iron(II) Complexes as Supramolecular Anion Capsules

AbstractTwo dimerized iron(II) complexes, [{Fe(L)(HL)2}{Fe(HL)3}](PF6)(BF4)2·5CH3CN·4H2O (1) and [{Fe(L)(HL)2}{Fe(HL)3}](PF6)(FeCl4)2 (2) {HL = 3‐(2‐pyridyl)‐5‐[4‐(diphenylamino)phenyl]‐1H‐pyrazole}, supported by triphenylamine‐derivatized bidentate ligands and encapsulating hexafluorophosphate ions were synthesized. The complex iron ions have octahedral coordination geometries in which they interact with six nitrogen atoms from three bidentate ligands. Both compounds have capsule‐like dimerized supramolecular structures, in which the arrangements of the bulky ligands of two discrete mononuclear complexes create a central cavity in which a single hexafluorophosphate ion is captured. The bidentate ligands interact with the anionic guest molecules through the hydrogen atoms of the ligand pyrazole moieties. Cryomagnetic studies reveal that both compounds show spin‐crossover behavior. Complex 1 showed quasi‐reversible spin‐crossover around 200–300 K, hindered by desolvation effects, whereas 2 showed reversible gradual spin‐crossover behavior. The electronic states of the iron ions resulting from the spin‐crossover were confirmed by X‐ray structure analyses and Mössbauer spectra.

New pyrazole derivatives containing 1,2,4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents

Azole class of compounds are well known for their excellent therapeutic properties. Present paper describes about the synthesis of three series of new 1,2,4-triazole and benzoxazole derivatives containing substituted pyrazole moiety (11a–d, 12a–d and 13a–d). The newly synthesized compounds were characterized by spectral studies and also by C, H, N analyses. All the synthesized compounds were screened for their analgesic activity by the tail flick method. The antimicrobial activity of the new derivatives was also performed by Minimum Inhibitory Concentration (MIC) by the serial dilution method. The results revealed that the compound 11c having 2,5-dichlorothiophene substituent on pyrazole moiety and a triazole ring showed significant analgesic and antimicrobial activity.

Crystal Structure Analysis of Ethyl 7-Phenyl-5- p-tolylpyrazolo[1,5-a]pyrimidine-3-carboxylate

The title compound, C22H19N3O2, was prepared from the three-component reaction. The structure of the title compound was established by single-crystal X-ray diffraction. The molecular structure shows that the phenyl ring is not coplanar with the pyrimidine ring. The torsion angle between the phenyl ring and pyrimidine ring is 147.01(15)°. The glide related molecules form one-dimensional corrugated tape-like structure via C–H···O hydrogen bonds along the crystallographic b-axis. These one-dimensional layers stack along the a-axis and form a corrugated layered structure and these layers are further stabilized by the weak C–H···π interactions. Also, it was found that the pyrazole moiety and p-toluyl groups of glide-related molecules are stacked through π···π interactions.

Synthesis and Fungicidal Activity of 1,3,4-Oxadiazole Derivatives Containing Pyrazole Moiety

A series of novel 1,3,4-oxadiazole derivatives were synthesized from acetylacetone, hydrazine hydrate by multi-step reactions. Their structures were characterized by 1 H NMR, MS and elemental analyses. The target compounds were evaluated for their fungicidal activities against Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans, Pseudoper- onospora cubensis and Sclerotinia sclerotiorum in vivo, and the results indicated that some of the title compounds displayed excellent fungicidal activities. Keywords 1,3,4-oxadiazole; pyrazole; synthesis; fungicidal activity

Activity landscape analysis, CoMFA and CoMSIA studies of pyrazole CB1 antagonists

Obesity and the metabolic syndrome are pandemic diseases with high morbidity and mortality. With the aim of discovering novel therapies for those diseases, the cannabinoid receptor 1 (CB1), which has been validated as a target for treating appetitive disorders, is now considered a novel target for the design of anti-obesity compounds. Our main goal was to determine the activity landscape of pyrazole derivatives and to develop reliable three-dimensional quantitative structure–activity relationship (3D-QSAR) models. Structure–activity similarity (SAS) maps of pyrazole analogs acting as antagonists of CB1 were constructed in order to identify activity cliffs, compounds that have high structural similarity with the rest of the compound set, but low activity similarity. According to the SAS maps, one molecule was identified as an outlier and before comparative molecular field analysis (COMFA) and comparative molecular similarity analysis (CoMSIA) 3D-QSAR models were derived. The best models resulted in an r 2 value of 0.992 and a q 2 of 0.766 for CoMFA and an r 2 of 0.983 and a q 2 of 0.681 for CoMSIA. Contour plots identified that the R3 position at the pyrazole moiety is an important feature for the optimization of the binding affinity to the CB1 receptor. According to our results, these models can be a useful tool for the design and prediction of novel CB1 antagonists.

ChemInform Abstract: Tricyclic Pyrazoles: An Efficient Approach to Cannabinoid Analogues with a Tricyclic Framework Incorporating the Pyrrole and Pyrazole Moieties.

AbstractThe synthesis of cyclic analogues (VIII) and (IX) of the potent and selective CB1 antagonist rimonabant is developed.

Synthesis of Planar Chiral N‐Heterocyclic‐Substituted Pyridinophanes

AbstractFour new planar chiral N‐heterocyclic‐substituted [2](1,4)benzene[2](2,5)pyridinophanes have been synthesized. With the attached pyrazole, triazole, tetrazole, and pyrimidine moieties, different N,N‐chelating ligands that vary in the number of enclosed nitrogen atoms, ring size, and electronic properties were added to a mostly neglected class of pyridinophanes. Additionally, the known synthesis of the pyridinophane scaffold was simplified considerably. With the acetyl, amino, and amido pyridinophane, various useful intermediates for new pyridinophane ligands were synthesized, which would allow for further investigations of this ligand system.

ChemInform Abstract: A Versatile Synthesis, PM3‐Semiempirical, Antibacterial, and Antitumor Evaluation of Some Bioactive Pyrazoles.

AbstractFourteen novel compounds incorporating pyrazolone or pyrazole moieties are synthesized and characterized, including quantum mechanical molecular orbital calculations.

ChemInform Abstract: Organocatalytic Asymmetric Domino Sulfa‐Michael—Aldol Reactions of 2‐Mercaptobenzaldehyde with α,β‐Unsaturated N‐Acylpyrazoles for the Construction of Thiochromane.

AbstractThe pivotal key is the introduction of the pyrazole moiety as H‐bond acceptor, which allows for better organization and activation.

ChemInform Abstract: Design, Synthesis and Biological Evaluation of a Novel Series of 1,3,4‐Oxadiazole Bearing N‐Methyl‐4‐(trifluoromethyl)phenyl Pyrazole Moiety as Cytotoxic Agents.

AbstractBy means of combinatorial synthesis, a new class of heterocycles is synthesized in which the potent oxadiazole moiety is linked to a biologically active N‐methylpyrazole moiety at C‐5 and different S‐substituted alkyl groups at C‐2.

Synthesis and Biological Evaluation of a Novel Series of Chalcones Incorporated Pyrazole Moiety as Anticancer and Antimicrobial Agents

A newly synthesized series of chalcone derivatives containing pyrazole rings were synthesized and evaluated for their cytotoxic activities in vitro against several human cancer cell lines. Most of the prepared compounds showed potential cytotoxicity against human breast cancer cell lines MCF-7, HEPG-2, and HCT-116. Also the compounds were evaluated as antimicrobial agents. The three compounds 3, 4, and 5 were proved to be better anticancer agents than the positive standard doxorubicin with IC50 values (4.7, 4.4, and 3.9μg/ml) against the same human cancer cell lines, whereas compounds 5 and 6 showed the most active antimicrobial compounds in comparison to the other chalcones.

Synthesis of novel Naphthalene COX inhibitors for anti-inflammatory activity

Micropropagation and shoot regeneration of Cistus creticus ssp. CreticusPanagiotis Madesis, Elpiniki Konstantinidou, Athanasios Tsaftaris, Irini Nianiou-Obeidat

ChemInform Abstract: Highly Efficient Catalytic Asymmetric Sulfa‐Michael Addition of Thiols to trans‐4,4,4‐Trifluorocrotonoylpyrazole.

A new protocol for the efficient construction of chiral trifluoromethylated building blocks was developed via organocatalyzed sulfa-Michael addition of thiols to the cost-efficient trans-trifluorocrotonamide. Introducing the pyrazole moiety is crucial to providing H-bond acceptor sites for better activation and hence affording comparable asymmetric induction with that obtained when employing the expensive cis-4,4,4-trifluorocrotonate as the Michael acceptor.

Tricyclic Pyrazoles: An Efficient Approach to Cannabinoid Analogues with a Tricyclic Framework Incorporating the Pyrrole and Pyrazole Moieties

In this paper we report the synthesis of some new cannabinoid analogues that share with rimonabant, a potent and selective CB1 antagonist, the 2,4-dichlorophenyl and piperidin-1-yl substituents on the pyrazole and amide nitrogens, respectively. The general synthesis involves the preparation of a cyclic ketone condensed with a pyrrole, followed by Claisen condensation with diethyl oxalate; from here, an aza-annulation reaction with a substituted hydrazine followed by an amidation step complete the synthesis.

SYNTHESIS AND TRANSFORMATION OF 4-(1Н-BENZIMIDAZOL-2-YL)-1-[3-(TRIFLUOROMETHYLPHENYL)]-2-PYRROLIDINONE

Study of chemical transformations of 4-(1Н-benzimidazol-2-yl)-1-[3-(trifluoromethylphenyl)]-2-pyrrolidinone was carried out. N-Substituted benzimidazole derivative was synthesized by alkylation of 1-(3-fluoromethylphenyl)-3-(1H-benzimidazol-2-yl)-5-oxopyrrolidine with ethyl chloroacetate in toluene in the presence of potassium carbonate, potassium hydroxide and a catalytic amount of tetrabutylammonium iodide. Carbohydrazide was obtained by reaction of the ester with hydrazine hydrate in refluxing 2-propanol. The hydrazones were synthesized by condensation of hydrazide with aromatic aldehydes were carried out. In the reaction with acetone and ethylmethylketone corresponding hydrazones were obtained. In analogous reactions with diketones – 2,4-pentanedione and 2,5-hexandiones – cyclic compounds with pyrrole and pyrazole moieties were synthesized. The results of this work have pointed to the possibility of synthesis of a wide range of 1,2-disubstituted benzimidazoles, containing 5-оxо-1-(3-trifluoromethylphenyl)pyrrolidine and hydrazone, pyrrole, pyrazole, benzimidazole, or triazine fragments.DOI: http://dx.doi.org/10.5755/j01.ct.60.2.1949

Efficient and Rapid Synthesis of Highly Functionalized Novel Symmetric 1,4-Dihydropyridines Using Glacial Acetic Acid as Solvent

A new series of 1,4-dihydropyridines bearing a pyrazole moiety in the 4-position were synthesized by a variation of the classical Hantzsch synthesis. The reaction of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4a–n with 3-amino crotononitrile in the presence of glacial acetic acid afforded novel 3,5-dicyano-2,6-dimethyl 1,4-dihydropyridines 5a–n. The procedure has short reaction time (15–20 min), easy workup, and good yield of product. The structures of all synthesized compounds were well characterized by mass, infrared, 1H and 13C NMR, and elemental analysis.