873697-71-3

873697-71-3 structure

Name: Omecamtiv mecarbil (CK-1827452)
Chemical Name: methyl 4-[[2-fluoro-3-[(6-methylpyridin-3-yl)carbamoylamino]phenyl]methyl]piperazine-1-carboxylate
CAS Number: 873697-71-3
Molecular Formula: C₂₀H₂₄FN₅O₃
Molecular Weight: 401.435
Catalog: Biochemical Inhibitor Transmembrane Transporters ATPase activator
Create Date: 2017-08-06 16:45:19
Modify Date: 2024-01-02 09:34:45
Omecamtiv mecarbil is a cardiac myosin activator.

Name	methyl 4-[[2-fluoro-3-[(6-methylpyridin-3-yl)carbamoylamino]phenyl]methyl]piperazine-1-carboxylate
Synonyms	methyl 4-(2-fluoro-5-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate omecamtiv mecarbil 1-Piperazinecarboxylic acid, 4-[[2-fluoro-3-[[[(6-methyl-3-pyridinyl)amino]carbonyl]amino]phenyl]methyl]-, methyl ester CK 1827452 Methyl 4-(2-fluoro-3-{[(6-methyl-3-pyridinyl)carbamoyl]amino}benzyl)-1-piperazinecarboxylate methyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate S2623_Selleck methyl 4-[(2-fluoro-3-{[(6-methyl(3-pyridyl))amino]carbonylamino}phenyl)methyl]piperazinecarboxylate Methyl 4-[[2-fluoro-3-[N'-(6-methylpyridin-3-yl)ureido]phenyl]methyl]piperazine-1-carboxylate

Description	Omecamtiv mecarbil is a cardiac myosin activator.
Related Catalog	Signaling Pathways >> Cytoskeleton >> Myosin Research Areas >> Cardiovascular Disease
In Vitro	Omecamtiv mecarbil (10 μM) reduces the maximal ATPase (kcat) 4.5-fold and dramatically reduces the actin concentration at which ATPase is half-maximal (KATPase) 30-fold. The Omecamtiv mecarbil-induced inhibition of the actin-activated ATPase is evaluated in a concentration-dependent manner to determine the EC50 (0.52 ± 0.10 μM). Omecamtiv mecarbil does not change the overall actin affinity. Omecamtiv mecarbil traps a population of myosin heads in a weak actin affinity state with slow product release. Omecamtiv mecarbil can reduce the actin sliding velocity more than 100-fold in the in vitro motility assay[3].
In Vivo	Omecamtiv mecarbil (100-1000 ng/mL) demonstrates concentration-dependent increases in FS in Sprague−Dawley rats model. Omecamtiv mecarbil demonstrates good PK parameters in both rats (Sprague−Dawley) and dogs (Beagle) with clearances of 22 and 7.2 mL/min/kg, volumes of 3.5 and 3.6 L/kg, and bioavailabilities (F%) of 100 and 80%, respectively[1]. Omecamtiv mecarbil does not affect the phosphorylation status of myofilament proteins in both WT and KO hearts as shown by the absence of significant differences between pre and post Omecamtiv mecarbil samples within WT and KO groups, or affect the force generation at maximal Ca2+ activation (pCa 4.5) in any of the groups. Omecamtiv mecarbil increases the responsiveness of the cardiac myofilaments to Ca2+ at submaximal Ca2+-activations[2].
References	[1]. Morgan BP, et al. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2010 Aug 20;1(9):472-7. [2]. Mamidi R, et al. Molecular effects of the myosin activator omecamtiv mecarbil on contractile properties of skinned myocardium lacking cardiac myosin binding protein-C. J Mol Cell Cardiol. 2015 Aug;85:262-72. [3]. Swenson AM, et al. Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem. 2017 Mar 3;292(9):3768-3778.

Density	1.3±0.1 g/cm3
Boiling Point	456.8±45.0 °C at 760 mmHg
Melting Point	180℃
Molecular Formula	C₂₀H₂₄FN₅O₃
Molecular Weight	401.435
Flash Point	230.1±28.7 °C
Exact Mass	401.186310
PSA	90.29000
LogP	1.36
Appearance	white solid
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.639
Storage condition	-20℃

732245-99-7

873697-70-2

~84%

873697-71-3

Literature: CYTOKINETICS, INC. Patent: WO2007/78839 A2, 2007 ; Location in patent: Page/Page column 48 ;

732245-99-7

942224-53-5

~70%

873697-71-3

Literature: Morgan, Bradley Paul; Muci, Alex; Lu, Pu-Ping; Kraynack, Erica Anne; Tochimoto, Todd; Morgans, David J. Patent: US2006/14761 A1, 2006 ; Location in patent: Page/Page column 33-34 ;