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Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates.

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In this paper, we report the synthesis and pharmacological evaluation of pyrazine N-acylhydrazone (NAH) derivatives (2a-s) designed as novel analgesic and anti-inflammatory drug candidates. This series was planned by molecular simplification of prototype 1 (LASSBio-1018), previously described as a

Anticancer and Anti-Inflammatory Activities of Some New Pyrazolo[3,4-b]pyrazines.

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New derivatives of pyrazolo[3,4-b]pyrazines and related heterocycles were synthesized using 5-amino-3-methyl-4-nitroso-1-phenyl-pyrazole (1) as a starting material. The 5-acetyl derivative 15 was shown to be a useful key intermediate for the synthesis of several derivatives of pyrazolopyrazines.

Pyrazine-Fused Triterpenoids Block the TRPA1 Ion Channel in Vitro and Inhibit TRPA1-Mediated Acute Inflammation in Vivo.

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TRPA1 is a nonselective cation channel, most famously expressed in nonmyelinated nociceptors. In addition to being an important chemical and mechanical pain sensor, TRPA1 has more recently appeared to have a role also in inflammation. Triterpenoids are natural products with anti-inflammatory and

Inhibition of lipopolysaccharide-induced prostaglandin E2 production and inflammation by the Na+/H+ exchanger inhibitors.

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We analyzed the effects of the Na+/H+ exchanger (NHE) inhibitor 3,5-diamino-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide hydrochloride (amiloride) and its analogs 5-(N,N-dimethyl)-amiloride (DMA) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on the lipopolysaccharide (LPS)-induced production

Efficient Access to Imidazo[1,2- a]pyridines/pyrazines/pyrimidines via Catalyst-Free Annulation Reaction under Microwave Irradiation in Green Solvent.

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An expeditious catalyst-free heteroannulation reaction for imidazo[1,2- a]pyridines/pyrimidines/pyrazines was developed in green solvent under microwave irradiation. Using H2O-IPA as the reaction medium, various substituted 2-aminopyridines/pyrazines/pyrimidines underwent annulation reaction with

Imidazo-pyrazine derivatives as potent CXCR3 antagonists.

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A general way of improving the potency of CXCR3 antagonists with fused hetero-bicyclic cores was identified. Optimization efforts led to the discovery of a series of imidazo-pyrazine derivatives with improved pharmacokinetic properties in addition to increased potency. The efficacy of the lead

Imidazo[1,2-a]pyrazine, Imidazo[1,5-a]quinoxaline and Pyrazolo[1,5-a]quinoxaline derivatives as IKK1 and IKK2 inhibitors.

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The transcription nuclear factor NF-κB plays a pivotal role in chronic and acute inflammatory diseases. Among the several and diverse strategies for inhibiting NF-κB, one of the most effective approach considered by the pharmaceutical industry seems to be offered by the development of IKK

[SCA 40 and derivatives: new bronchodilators in an imidazo(1,2-a)pyrazine series].

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Asthma is a complex disease characterised by bronchoconstriction and airways inflammation. Recent advances in medicinal chemistry will surely lead to a better reappraisal of therapeutic strategies. 8-(Methylamino)imidazo(1,2-a)pyrazines with substitution either on position 2 or 3 powerful relaxing

Inhibitory effects of bioactive leads isolated from Pseudomonas aeruginosa PS3 and Pseudomonas fluorescens PS7 on MAP kinases and down regulation of pro inflammatory cytokines (TNF-α, IL-1β) and mediators (NO, iNOS and COX).

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Pure lead molecules, showing anti-inflammatory effect were isolated from the marine Pseudomonas aeruginosa PS3 (GenBank Accession No. EF488968) and Pseudomonas fluorescens PS7 (GenBank Accession No. EF488969) using solvent extraction procedures, subsequent column fractionation, followed by bio

Pyrido[2,3-b]pyrazines, discovery of TRPV1 antagonists with reduced potential for the formation of reactive metabolites.

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The transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is a non-selective cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antagonists is under investigation in an attempt

Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro-inflammatory cytokine inhibitors.

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A series of heterocyclic derivatives including indoles, pyrazines along with oximes and esters were synthesized from lupeol and evaluated for anti-inflammatory activity through inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 and J774A.1 cells. All the

Research on heterocyclic compounds. X.-Imidazo[1,2-a]pyrazine derivatives: synthesis and antiinflammatory activity.

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Since we had previously observed the considerable anti-inflammatory activity of imidazo[1,2-a]pyrazine 2-acetic acid, we prepared a series of imidazo[1,2-a]pyrazine derivatives, bearing some substituents on the pyrazine ring and a carboxylic, acetic or alpha-methylacetic moiety on the imidazole

Bronchodilator and anti-inflammatory activities of SCA40: studies in human isolated bronchus, human eosinophils, and in the guinea-pig in vivo.

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There is currently interest in the use of inhibitors of cyclic nucleotide phosphodiesterases (PDE) as potential anti-asthma agents. In this study we examined the effects of SCA40 (6-bromo-8-methylaminoimidazol-[1,2-a] pyrazine-2-carbonitrile), a preferential inhibitor of PDE 3 also endowed with PDE

Identification of pyrazine-based TrkA inhibitors: design, synthesis, evaluation, and computational modeling studies.

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Trk receptors play a key role in the development and maintenance of neuronal networks. Recent evidence suggests that the Trk family, specifically TrkA, is an important driver for tumour growth, inflammatory and neuropathic pain, and chemoresistance. Through a computational screen, a novel Trk active

Pyrazine derivatives: a patent review (2008 - present).

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BACKGROUND Pyrazines derivatives are well-known and important two-nitrogen-containing six-membered ring aromatic heterocyclic compounds and can carry substituents at one or more of the four ring carbon atoms. Pyrazines are a class of compounds that occur in nature and various methods have been

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