156897-06-2 Usage
Description
Licofelone is a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LO) pathways, which plays a significant role in reducing inflammation and pain. It is a yellowish solid that effectively decreases the levels of prostaglandin E2, leukotriene B4, and lipoxins, while also preventing lipopolysaccharide-stimulated interleukin-1β (IL-1β) expression. Licofelone demonstrates a unique property of causing little or no damage to the gastric mucosa, which is an advantage over other non-steroidal anti-inflammatory drugs.
Uses
Used in Pharmaceutical Industry:
Licofelone is used as an anti-inflammatory agent for its ability to inhibit both COX and LO pathways, reducing inflammation and pain effectively. Its IC50 values for inhibition of human thrombocyte COX and human 5-LO are 0.16 μM and 0.23 μM, respectively, indicating its potency in this application.
Additionally, Licofelone is used as a gastric protective agent due to its minimal damage to the gastric mucosa in rabbit parietal cells. This property is attributed to its effects on acid-secretory mechanisms, which are mediated by the inhibition of 5-LO activity.
in vitro
the 5-lox and cox inhibitory effect of licofelone was firstly identified via bovine thromobocyte intact cell assay and intact bovine pmn leukocytes. licofelone was also reported to inhibit pge2 in a dose-dependent manner in human whole blood assay. moreover, licofelone was found to suppress in vitro generation of reactive oxygen species and to reduce release of elastase from pmn leukocytes. all above findings revealed that licofelone had an inhibitory effect on cox-1/-2 and 5-lox. [1]
in vivo
the pharmacodynamic properties of licofelone were evaluated in various animal models and compared with those of commonly used nsaids. based on studies from a rat model of incisional pain, orally administration of licofelone had a longer duration of action and was more effective than indomethacin and zileuton. [1]
IC 50
inhibitor of cox-1, cox-2 and 5-lox with ic50 values of 0.16 m, 0.37 m and 0.23 m respectively in human.
references
[1]kulkarni sk and singh vp. licofelone-a novel analgesic and anti-inflammatory agent. curr top med chem. 2007; 7(3): 251-63.
Check Digit Verification of cas no
The CAS Registry Mumber 156897-06-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,6,8,9 and 7 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 156897-06:
(8*1)+(7*5)+(6*6)+(5*8)+(4*9)+(3*7)+(2*0)+(1*6)=182
182 % 10 = 2
So 156897-06-2 is a valid CAS Registry Number.
InChI:InChI=1/C23H22ClNO2/c1-23(2)13-19-22(15-6-4-3-5-7-15)21(16-8-10-17(24)11-9-16)18(12-20(26)27)25(19)14-23/h3-11H,12-14H2,1-2H3,(H,26,27)
156897-06-2Relevant articles and documents
Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives
Liu, Wukun,Zhou, Jinpei,Bensdorf, Kerstin,Zhang, Huibin,Liu, Haoran,Wang, Yubin,Qian, Hai,Zhang, Yanchun,Wellner, Anja,Rubner, Gerhard,Huang, Wenlong,Guo, Cancheng,Gust, Ronald
, p. 907 - 913 (2011/04/19)
A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7- phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (8f) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo.
Synthesis and biological evaluation of licofelone derivatives as anticancer and anti-inflammatory agents
Liu, Wukun,Zhou, Jinpei,Zhang, Huibin,Qian, Hai,Yin, Jiahan,Bensdorf, Kerstin,Gust, Ronald
experimental part, p. 911 - 917 (2012/07/03)
Two C5-substituted licofelone derivatives were developed and investigated for cytotoxicity against mammary (MCF-7 and MDA-MB 231) as well as colon carcinoma (HT-29) cancer cells. Both compounds were at least 2-fold more active than 5-fluorouracil (5-FU) and licofelone against mammary carcinoma cells. At HT-29 cells, they were less active, but nevertheless distinctly as active as 5-FU and still 2-fold more active than licofelone. However, variation of the C5- carboxylic group results in an occasionally remarkable decrease of anti-inflammatory potency in in vitro and in vivo.
A synthesis of licofelone using Fenton's reagent
Rádl, Stanislav,?erny, Josef,Klecán, Ond?ej,Stach, Jan,Pla?ek, Luká?,Mandelová, Zuzana
, p. 5316 - 5318 (2008/12/22)
An efficient synthesis of licofelone, an anti-inflammatory drug currently undergoing phase-III clinical studies, based on Fenton-type radical alkylation of 2,3-dihydro-1H-pyrrolizine 3 with iodoacetonitrile or iodoacetates is reported. The iodoacetates can be replaced by NaI and by the corresponding bromoacetate.