ChemInform Abstract: Chemoselective Synthesis of 3- and 5-Pyrazolylacetates (original) (raw)
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Pyrazoles as potential anti-angiogenesis agents: a contemporary overview
Frontiers in Chemistry, 2014
Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently, several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research.
Journal of Neurochemistry, 2008
3-Azidophenyl-and 3-isothiocyanatophenyland 2-(5Ј-azidopentyl)-and 2-(5Ј-isothiocyanatopentyl)pyrazoles were synthesized to determine whether these compounds could behave as covalently binding ligands for the CB 1 cannabinoid receptor in rat brain membranes. Heterologous displacement of [ 3 H]CP55940 indicated that the apparent affinity of these compounds for the CB 1 receptor was similar to that of the parent compound, SR141716A, with the exception of the 3-isothiocyanato derivatives, which showed a 10-fold loss of affinity. The 3-azidophenyl and 3-isothiocyanatophenyl compounds behaved as antagonists against the cannabinoid agonist desacetyllevonantradol in activation of G proteins [guanosine 5Ј-O-(␥-[ 35 S]thio)triphosphate ([ 35 S]GTP␥S) binding] and regulation of adenylyl cyclase. The 2-(5Ј-azidopentyl)-and 2-(5Ј-isothiocyanatopentyl)pyrazoles were poor antagonists for [ 35 S]GTP␥S binding, and both compounds failed to antagonize the cannabinoid regulation of adenylyl cyclase. After incubation with the isothiocyanato analogues or UV irradiation of the azido analogues, the 3-substituted aryl pyrazoles formed covalent bonds with the CB 1 receptor as evidenced by the loss of specific binding of [ 3 H]CP55940. In the case of the isothiocyanato analogues, the log concentrationresponse curve for cannabinoid-stimulated [ 35 S]GTP␥S binding was shifted to the right, indicating that loss of receptors compromised signal transduction capability. These irreversibly binding antagonists might be useful tools for the investigation of tolerance and receptor down-regulation in both in vitro and in vivo studies.
Cosmetic preservation and structure-activity relationships of 4-diazo-pyrazole-5-carboxamides
International journal of cosmetic science, 1995
Summary Diazoles have attracted considerable attention for a long time owing to their potentially interesting chemical, biochemical, and medicinal properties. We have reported the synthesis and in vitro antibacterial activity of a new series of (N-substituted)-3-methyl-4-diazo-5-pyrazolecarboxamides 1a-n along with their quantitative structureactivity study. There was a trend towards a better Gram-negative activity with decreasing molecular refraction values of the substituents on the carboxamidic moiety and a better Gram-positive activity with increasing values of IR carbonyl shift. The compounds which displayed the broadest antibacterial spectrum were 3-methyl-4-diazo-5-pyrazolecarboxamides substituted with 2-pyridinyl and 3-isoxazolyl moieties, making evident the structural requirement of a heterocyclic substituent with aminic function located in the ortho position with respect to heteroatom(s). The introduction of new substituents with different lipophilic properties in place of...
Journal of medicinal …, 1992
Ga-e, g, i and of pyrazolo [4, 3-d]-1, 2, 3-triazin-4-ones 12f-1 mediated by silylation with hexamethyldisilazane, with 1-~-0-acetyl-2, 3, 5-tri-~-benzoyl-~-ribofuranose, gave in good yields the corresponding glycosides 7a-e, g, 8g, i, 13f, h, k, and 14f, but could not be ...
Monatshefte fur Chemie, 2007
The syntheses of several new 3-and 5-(4chloro-2-hydroxyphenyl)-5-and -3-(2,4-dichlorophenyl)-1alkylpyrazoles are reported. These syntheses started from simple chlorophenols, 2,4-dichlorobenzaldehyde or ethyl 2,4dichlorobenzoate in order to prepare pyrazoles bearing three and four chloro substituents in certain positions. The affinity of these compounds towards the CB 1 type cannabinoids receptors was then evaluated in human brain tissues (frontal cortex). The results showed that some of the compounds exhibit affinity towards this kind of receptors in the micromolar range.
2012
A number of 5-oxo-pyrazolo[1,5-c]quinazolines (series B-1), bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-8) but also a carboxylate group (9-14), were designed as hA 3 AR antagonists. This study produced some interesting compounds endowed with good hA 3 receptor affinity and high selectivity, being totally inactive at all the other AR subtypes. In contrast, the corresponding 5ammino derivatives (series B-2) do not bind or bind with very low affinity at the hA 3 AR, the only exception being the 5-N-benzoyl compound 19 that shows a hA 3 K i value in the high l-molar range. Evaluation of the synthetic intermediates led to the identification of some 5(3)-(2-aminophenyl)-3(5)-(hetero)arylpyrazoles 20-24 with modest affinity but high selectivity toward the hA 3 AR subtype. Molecular docking of the herein reported tricyclic and simplified derivatives was carried out to depict their hypothetical binding mode to our model of hA 3 receptor.
New strategies for the synthesis of A3 adenosine receptor antagonists
Bioorganic & Medicinal Chemistry, 2003
New A 3 adenosine receptor antagonists were synthesized and tested at human adenosine receptor subtypes. An advanced synthetic strategy permitted us to obtain a large amount of the key intermediate 5 that was then submitted to alkylation procedures in order to obtain the derivatives 6-8. These compounds were then functionalised into ureas at the 5-position (compounds 9-11, 18 and 19) to evaluate their affinity and selectivity versus hA 3 adenosine receptor subtype; in particular, compounds 18 and 19 displayed a value of affinity of 4.9 and 1.3 nM, respectively. Starting from 5, the synthetic methodologies employed permitted us to perform a rapid and a convenient divergent synthesis. A further improvement allowed the regioselective preparation of the N 8substituted compound 7. This method could be used as an helpful general procedure for the design of novel A 3 adenosine receptor antagonists without the difficulty of separating the N 8 -substituted pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines from the corresponding N 7 -isomers. #
Journal of Pharmacy Research 2011,4(12),4654-4657 4654-4657 Research Article ISSN: 0974-6943 Available online through www.jpronline.info, 2011
OBJECTIVE: Considerable interest have been focused on isoxazole and pyrazole structures, which has been known to possess a broad spectrum of biological activities such as analgesic, anti-inflammatory, anticancer,etc, (1). All the isoxazole and pyrazole derivatives were prepared from the appropriate b-diketones by reaction with Hydroxylamine Hydrochloride and Hydrazine hydrate respectively.ABSTRACT : In view of the biological importance it was proposed to prepare some Diaryl isoxazoles and pyrazoles and study their biological activities. All the isoxazole and pyrazole derivatives were prepared from the appropriate b- diketones by reaction with Hydroxylamine Hydrochloride and Hydrazine hydrate respectively, (2). The structures of the synthesized compounds were determined by using different analytical techniques like 1HNMR, IR and Mass spectroscopy. Almost all the non steroidal anti-inflammatory drugs (NSAID’S) under current clinical usage are highly acidic in nature and suffer from a common drawback of gastrointestinal toxicity, thus indicating a clear need to develop a non-acidic nonsteroidal anti-inflammatory agent, (3). Among all the compounds tested, compounds 4, 5, 6, 7, 8, 9, showed significant anti inflammatory activity. It was concluded that pyrazoles showed significant anti inflammatory activity than that of Isoxazoles.PRINCIPLE CONCLUSION: Di chloro substituted benzene ring at position 3 of the Pyrazoles and Isoxazoles exhibited moderate antibacterial activity and antifungal activity when compared to that of mono chloro substituted benzene ring at position 3 of Isoxazole and pyrazoles. 3, 4 di chloro substituted benzene ring at position 3 of the pyrazoles and Isoxazoles showed significant antifungal activity. Key words: Isoxazole, pyrazole, anti inflammatory, bactericidal and fungicidal