Synthesis, anti-inflammatory, cyclooxygenases inhibitions assays and histopathological study of poly-substituted 1,3,5-triazines: Confirmation of regiospecific pyrazole cyclization by HMBC

被引：50

作者：

Elshemy, Heba A. H. ^{[1
]}

Abdelall, Eman K. A. ^{[1
]}

Azouz, Amany A. ^{[2
]}

Moawad, Abeer ^{[3
]}

Ali, Waleed A. M. ^{[4
]}

Safwat, Nesreen M. ^{[5
]}

机构：

[1] Beni Suef Univ, Dept Organ Pharmaceut Chem, Fac Pharm, Bani Suwayf 62514, Egypt

[2] Beni Suef Univ, Dept Pharmacol, Fac Pharm, Bani Suwayf 62514, Egypt

[3] Beni Suef Univ, Dept Pharmacognosy, Fac Pharm, Bani Suwayf 62514, Egypt

[4] Cairo Gen Hosp, Biochem Lab, Cairo, Egypt

[5] Beni Suef Univ, Dept Pathol, Fac Vet Med, Bani Suwayf 62514, Egypt

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 127卷

关键词：

S-Triazines; COX-2; inhibitors; Anti-inflammatory activity; Enaminone; HMBC; Histopathology; CELECOXIB ANALOGS; RING FORMATION; 2D NMR; DERIVATIVES; 5-LIPOXYGENASE; PYRIMIDINE; LIABILITY; COX-2;

D O I：

10.1016/j.ejmech.2016.12.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Three novel triazines series were prepared. These series are pyrazolines (4a and 4b), pyrazoles (6a, 6b and 8a-d) and isoxazoles (7a and 7b). Such series were designed as COX-2 inhibitors. All compounds were characterized by using spectroscopic methods and elemental analysis. Regarding COX-2, compounds 5b, 4a and 3b were the most active with IC50 in the range of 0.55-0.87 mu M. Most of synthesized compounds were relatively more potent to celecoxib (0.78 mu M), diclofenac (2.94 mu M) and indomethacin (7.24 mu M). A molecular modeling study was performed for the most active compounds. Histopathological evaluation also was done to estimate the safety of compounds. Finally, structure elucidation of pyrazole 8 was studied by 2D NMR. (C) 2016 Published by Elsevier Masson SAS.

引用

页码：10 / 21

页数：12

共 23 条

[1] Synthesis and cytotoxic activity of new pyrazolo[1,5-a]pyrimidines and determination of pyrimidine regiospecific ring formation with 2D NMR [J].

Abdelall, Eman K. A. ;

Philoppes, John N. .

ARKIVOC, 2016, :210-224

[2] Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR [J].

Abdelall, Eman K. A. ;

Kamel, Gehan M. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2016, 118 :250-258

[3] Cyclooxygenase-2 and 15-lipoxygenase inhibition, synthesis, anti-inflammatory activity and ulcer liability of new celecoxib analogues: Determination of region-specific pyrazole ring formation by NOESY [J].

Abdelall, Eman K. A. ;

Lamie, Phoebe F. ;

Ali, Waleed A. M. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (12) :2893-2899

[4] Synthesis and Antimicrobial Activity of Some New 5-Arylazothiazole, Pyrazolo[1,5-a] Pyrimidine, [1,2,4]Triazolo[4,3-a]Pyrimidine, and Pyrimido[1,2-a]Benzimidazole Derivatives Containing the Thiazole Moiety [J].

Abdelhamid, Abdou O. ;

Abdelall, Eman K. A. ;

Abdel-Riheem, Nadia A. ;

Ahmed, Sayed A. .

PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 2010, 185 (04) :709-718

[5] Reactions with Hydrazonoyl Halides 62: Synthesis and Antimicrobial Evaluation of Some New Imidazo [1,2-a]pyrimidine, Imidazo [1,2-a]pyridine, Imdazo [1,2-b]pyrazole, and Quinoxaline Derivatives [J].

Abdelhamid, Abdou O. ;

Abdelall, Eman K. A. ;

Zaki, Yasser H. .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2010, 47 (02) :477-482

[6] Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,3,5-triarylpyrazoline and 1,5-diarylpyrazole derivatives as selective COX-2 inhibitors [J].

Abdellatif, Khaled R. A. ;

Abdelall, Eman K. A. ;

Fadaly, Wael A. A. ;

Kamel, Gehan M. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (02) :406-412

[7] Synthesis, cyclooxygenase inhibition, and anti-inflammatory evaluation of novel diarylheterocycles with a central pyrazole, pyrazoline, or pyridine ring [J].

Abdellatif, Khaled R. A. ;

Abdelall, Eman K. A. ;

Fadaly, Wael A. A. ;

Kamel, Gehan M. .

MEDICINAL CHEMISTRY RESEARCH, 2015, 24 (06) :2632-2644

[8]

Anjani S., 2011, DER PHARM CHEM, V3, P317

[9] Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs [J].

Charlier, C ;

Michaux, C .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (7-8) :645-659

[10]

Cyrous O. K., 2009, TETRAHEDRON LETT, V50, P5332

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