Synthesis and Structure−Activity Relationship of a New Series of COX-2 Selective Inhibitors:  1,5-Diarylimidazoles

Almansa, Carmen; Alfón, José; Arriba, Alberto Fernández de; Cavalcanti, F. L.; Escamilla, Ignasi; Gómez, Luis Alberto; Miralles, A; Soliva, Robert; Bartrolí, Javier; Carceller, Elena; Merlos, Manuel; García-Rafanell, Julián

doi:10.1021/jm030765s

Cited by 128 publications

(60 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[22,23] To test this hypothesis, we reacted 10i with 1.05 equiv. of Nbromosuccinimide (NBS) in acetonitrile at room temperature and obtained a mixture of 4-bromo derivative 11g and a small amount (about 3-4 %) of 2-bromo derivative 18.…”

Section: Synthesis Of 5-aryl-4-bromo-1-methyl-1h-imidazolesmentioning

confidence: 99%

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

et al. 2008

View full text Add to dashboard Cite

A general and efficient three-step procedure for the highly regioselective synthesis of 1-methyl-1H-imidazoles possessing electron-rich, electron-neutral and/or electron-deficient aryl moieties at their 4- and 5-position is described. The first step involves the Pd-catalyzed direct C-5 arylation of commercially available 1-methyl-1H-imidazole with aryl bromides and the second and third step of the sequence involve the selective C-4 bromination of the resulting 5-aryl-1-methyl-1H-imidazoles with NBS followed by a PdCl2(dppf)-catalyzed Suzuki-type reaction between 5-aryl-4-bromo-1-methyl-1H-imidazoles and arylboronic acids under phase-transfer conditions. Two so prepared 4,5-diaryl-1-methyl-1H-imidazoles, which can be regarded as Z-restricted analogues of naturally-occurring combretastatin A-4 (CA-4), have proven to be highly cytotoxic against a variety of human tumor cell lines and one of these derivatives has been shown to be more cytotoxic than CA-4 and all of the imidazole derivatives investigated in the literature so far

show abstract

Section: Synthesis Of 5-aryl-4-bromo-1-methyl-1h-imidazolesmentioning

confidence: 99%

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Recently, it was discovered that COX exist in two isoforms, COX-1 and COX-2, which are regulated differently [6,7]. COX-1 provides cytoprotection in the gastrointestinal tract whereas inducible COX-2 mediates inflammation [8,9]. Thus the discovery of COX-2 provided the rationale for the development of drugs devoid of GI disorders while retaining clinical efficacy as anti-inflammatory agents.…”

Section: Introductionmentioning

confidence: 99%

Non‐carboxylic Analogues of Naproxen: Design, Synthesis, and Pharmacological Evaluation of some 1,3,4‐Oxadiazole/Thiadiazole and 1,2,4‐Triazole Derivatives

Amir

Kumar

Javed

2007

Archiv der Pharmazie

View full text Add to dashboard Cite

A series of substituted 1,3,4-oxadiazole (2-7 and 14-19), 1,2,4-triazole (20-25), and 1,3,4-thiadiazole (26-31) derivatives of naproxen have been synthesized by cyclization of 2-(6-methoxy-2-naphthyl)propanoic acid hydrazide 1 and N(1)[2-(6-methoxy-2-naphthyl) propanoyl]-N(4)-alkyl/aryl-thiosemicarbazides (8-13) under various reaction conditions. All the compounds were screened for their anti-inflammatory activity by carrageenan-induced rat paw edema test method. Compounds showing high anti-inflammatory activity were also tested for their analgesic, ulcerogenic, and lipid peroxidation. Few of the synthesized compounds showed significant anti-inflammatory and analgesic activities along with reduced ulcerogenic effect and lipid peroxidation.

show abstract

“…Recently, it was discovered that COX exists in two isoforms, COX-1 and COX-2, which are regulated differently [7,8]. COX-1 provides cytoprotection in the gastrointestinal (GI) tract whereas inducible COX-2 mediates inflammation [9,10]. Since most of the NSAIDs in the market show greater selectivity for COX-1 than COX-2 [11], chronic use of NSAIDs may elicit appreciable GI irritation, bleeding and ulceration [12].…”

mentioning

confidence: 99%

Anti‐inflammatory and Gastro Sparing Activity of Some New Indomethacin Derivatives

Amir

Kumar

2005

Archiv der Pharmazie

View full text Add to dashboard Cite

Indomethacin is a non-steroidal anti-inflammatory drug but its use is associated with high degree of gastric toxicity therefore it is prescribed only in severe conditions. In order to reduce the gastric toxicity of indomethacin, various oxadiazole, triazole, thiadiazole and triazine derivatives have been synthesized. Out of thirteen cyclized derivatives, eleven were screened for anti-inflammatory activity by Winter et al. method. Four compounds showed highly significant activity and were further tested for analgesic, ulcerogenic and lipid peroxidation activities. The tested compounds showed anti-inflammatory activities in the range from about 32% to 85% as compared to that of indomethacin of about 96%. The compounds showing high anti-inflammatory activity also exhibited reduction in severity index. These compounds also produced less malondialdehyde content in gastric mucosa than the standard drug indomethacin. The study showed that the compounds inhibited the induction of gastric mucosal lesions and it can be suggested from our results that their protective effects may be related to inhibition of lipid peroxidation in the gastric mucosa.

show abstract

Synthesis and Structure−Activity Relationship of a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles

Cited by 128 publications

References 38 publications

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

Non‐carboxylic Analogues of Naproxen: Design, Synthesis, and Pharmacological Evaluation of some 1,3,4‐Oxadiazole/Thiadiazole and 1,2,4‐Triazole Derivatives

Anti‐inflammatory and Gastro Sparing Activity of Some New Indomethacin Derivatives

Contact Info

Product

Resources

About