Reference

Ligand-based design, synthesis and primary in vivo screening of pyrrole derivatives as potential tricyclic anti-inflammatory agents

All Rights Reserved. Ligand-based design, synthesis and primary in vivo screening of pyrrole derivatives as potential tricyclic anti-inflammatory agents. There are some commonly used reagents like 169590-42-5 in this article. Bijev, Atanas; Yaneva, Diana; Bocheva, Adriana; Stoev, Georgi ( Department of Organic Synthesis and Fuels, University of Chemical Technology and Metallurgy, Sofia, Bulg.). Arzneimittel Forschung, 56(11), 753-759 (English) 2006 Editio Cantor Verlag. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 27, 28 Twelve new compds. were designed as 5-aryl-1H-pyrrole analogs of celecoxib (CAS 169590-42-5) and were synthesized by Paal-Knorr cyclization in three series according to 1H-substitution: derivs. with salicylic acid, pyrazolone or isonicotinamide residues. The av. physicochem. and steric similarity between the prototype and the new analogs (completed with two previously synthesized related products) was assessed to be 82 % and therefore considered as a reliable prerequisite for spatial compatibility and effective binding to the cyclooxygenase (COX) enzymes. The anti-inflammatory effects were detd. in acute inflammation model using the carrageenan-induced rat paw edema assay on male Wistar rats (180-200 g) at doses of 10, 20 and 40 mg/kg, i.p. Six of the new products showed higher percent of inhibition (up to 100 %) compared to the highly selective COX-2 inhibitor celecoxib and the nonselective indometacin (CAS 53-86-1) used as ref. compds. Et 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-4-pyrazolyl)-2-methyl-5- phenyl-1H-3-pyrrolecarboxylate (2b), Et 5-(4-chlorophenyl)-2-methyl-1-[(4-pyridylcarbonyl)amino]-1H-3-pyrrolec arboxylate (3c) and 5-[3-acetyl-2-methyl-5-(4-methylphenyl)-1H-1-pyrrolyl]-2-hydroxybenzoic acid (4b) were pointed out as the most active representatives of each of the three tested sub-series. .

Analgesic effects of some newly synthesized pyrrole derivatives in rats

All Rights Reserved. Analgesic effects of some newly synthesized pyrrole derivatives in rats. Bocheva, A.; Dzambazova-Maximova, E.; Hadjiolova, R.; Tzvetkova, M.; Yaneva, D.; Bijev, A. (Department of Pathophysiology, Medical University of Sofia, Sofia 1431, Bulg.). Dokladi na Bulgarskata Akademiya na Naukite, 59(1), 99-104 (English) 2006 Izdatelstvo na Bulgarskata Akademiya na Naukite. CODEN: DBANEH. ISSN: 1310-1331. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Pain, edema and fever are the signs and symptoms of inflammation. Prostaglandins (PGs) are well established as mediators of several components of the inflammatory response. Particularly, PGs potentiate the microvascular effects of other mediators such as bradykinin, substance P and histamine. These mediators also induce pain in inflammatory sites and this component is also potentiated by PGs. Although PGs are not direct analgesic agents as are bradykinin, substance P and histamine, they nevertheless induce a state of hyperalgesia in which previously non-painful stimuli are now perceived as painful in both animal models and in human subjects. It is known that nonsteroidal anti-inflammatory drugs (NSAID) inhibited the synthesis of prostaglandins and their derivs. We studied nine newly synthesized pyrrole derivs. based on the architecture of tricyclic COX-2 inhibitors and bonded to salicylic (D37, D84, D87), isonicotinamide (D51, D52, D53) or pyrazolinone (D54, D71, D73) moiety for analgesic activity. 69-72-7 and 169590-42-5 are cas registry numbers of chemicals which are used as reagents here. The effects on nociception were examd. in male Wistar rats by Randall-Selitto paw-pressure test. The compds. were administrated i.p. (i.p.) in doses of 10, 20 and 40 mg/kg. The results showed that pyrrole derivs. based on the architecture of tricyclic COX-2 inhibitors increased significantly the pain threshold. This effect is dose related and more pronounced in inflamed paw. .