623152-17-0 Usage
Biological Activity
bms-582949 is a p38 mapk inhibitorp38r map kinase plays a key role in regulating the biosynthesis of various inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-1β. thus, p38r inhibitors are considered as a promising therapy for inflammatory disease treatment.
in vitro
bms-582949 was found to be 450-fold selective over jnk2, a map kinase involved in inflammation, and 190-fold selective against raf. moreover, the binding mode of bms-582949 with p38r was further demonstrated by x-ray crystallographic analyses [1].
in vivo
in a pseudoestablished rat adjuvant arthritis model, bms-582949 at doses of 10 and 100 mg/kg was found to display dose-dependent reduction in paw swelling with qd dosing. in addition, with bid dosing at doses of 1 and 5 mg/kg, bms-582949 showed improved efficacy, resulting in great reduction in paw swelling. moreover, the statistically significant reduction in paw swelling was also observed with the treatment of bms-582949 at doses as low as 0.3 mg/kg bid [1].
IC 50
13 nm
references
[1]. liu c, et al. discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl- n-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (bms-582949), a clinical p38α map kinase inhibitor for the treatment of inflammatory diseases. j med chem. 2010 sep 23;53(18):6629-39.[2]. emami h, et al. the effect of bms-582949, a p38 mitogen-activated protein kinase (p38 mapk) inhibitor on arterial inflammation: a multicenter fdg-pet trial. atherosclerosis. 2015 jun;240(2):490-6.
Check Digit Verification of cas no
The CAS Registry Mumber 623152-17-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,2,3,1,5 and 2 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 623152-17:
(8*6)+(7*2)+(6*3)+(5*1)+(4*5)+(3*2)+(2*1)+(1*7)=120
120 % 10 = 0
So 623152-17-0 is a valid CAS Registry Number.
623152-17-0Relevant articles and documents
Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N- propylpyrrolo[1,2-f ][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases
Liu, Chunjian,Lin, James,Wrobleski, Stephen T.,Lin, Shuqun,Hynes, John,Wu, Hong,Dyckman, Alaric J.,Li, Tianle,Wityak, John,Gillooly, Kathleen M.,Pitt, Sidney,Shen, Ding Ren,Zhang, Rosemary F.,McIntyre, Kim W.,Salter-Cid, Luisa,Shuster, David J.,Zhang, Hongjian,Marathe, Punit H.,Doweyko, Arthur M.,Sack, John S.,Kiefer, Susan E.,Kish, Kevin F.,Newitt, John A.,McKinnon, Murray,Dodd, John H.,Barrish, Joel C.,Schieven, Gary L.,Leftheris, Katerina
experimental part, p. 6629 - 6639 (2010/12/18)
The discovery and characterization of 7k (BMS-582949), a highly selective p38α MAP kinase inhibitor that is currently in phase II clinical trials for the treatment of rheumatoid arthritis, is described. A key to the discovery was the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously reported clinical candidate p38α inhibitor. Unlike alkyl and other cycloalkyls, the sp2 character of the cyclopropyl group can confer improved H-bonding characteristics to the directly substituted amide NH. Inhibitor 7k is slightly less active than 1a in the p38α enzymatic assay but displays a superior pharmacokinetic profile and, as such, was more effective in both the acute murine model of inflammation and pseudoestablished rat AA model. The binding mode of 7k with p38α was confirmed by X-ray crystallographic analysis.
PROCESS FOR PREPARING PYRROLOTRIAZINE ANILINE COMPOUNDS USEFUL AS KINASE INHIBITORS
-
Page/Page column 13, (2010/10/19)
-
PYRROLO-TRIAZINE ANILINE COMPOUNDS USEFUL AS KINASE INHIBITORS
-
Page/Page column 44, (2008/06/13)
-
