methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate

• ChemBase ID: 73097
• Molecular Formular: C20H24FN5O3
• Molecular Mass: 401.4346632
• Monoisotopic Mass: 401.18631787
• SMILES: c1(ncc(cc1)NC(=O)Nc1c(c(ccc1)CN1CCN(CC1)C(=O)OC)F)C
• Canonical SMILES: COC(=O)N1CCN(CC1)Cc1cccc(c1F)NC(=O)Nc1ccc(nc1)C
• InChI: InChI=1S/C20H24FN5O3/c1-14-6-7-16(12-22-14)23-19(27)24-17-5-3-4-15(18(17)21)13-25-8-10-26(11-9-25)20(28)29-2/h3-7,12H,8-11,13H2,1-2H3,(H2,23,24,27)
• InChIKey: RFUBTTPMWSKEIW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate
• IUPAC Traditional name: methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate
• Synonyms: CK-1827452; Omecamtiv mecarbil

Database IDs

• CAS Number: 873697-71-3
• PubChem SID: 162038017
• PubChem CID: 11689883

CALCULATED PROPERTIES

• Acid pKa: 10.312983
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 1.3768723
• LogD (pH = 7.4): 1.8016069
• Log P: 1.8097566
• Molar Refractivity: 109.1914 cm^3
• Polarizability: 40.259735 Å^3
• Polar Surface Area: 86.8 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: calcium channel

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2623

Research Area

• Description: Cancer

Biological Activity

• Description: Omecamtiv mecarbil (CK-1827452) is a specific cardiac myosin activator and a clinical drug for left ventricular systolic heart failure.
• In Vitro: In vitro, Omecamtiv mecarbil selectively activates cardiac myosin by increasing the myosin ATPase rate. ^[1] In isolated cardiac myocytes, Omecamtiv mecarbil results in increase of myocyte contractility and overcomes of the myosin inhibitor BDM without increasing the calcium transient or inhibiting the PDE pathway. ^[1]
• In Vivo: Omecamtiv mecarbil significantly increases fractional shortening starting at 0.4 mM plasma concentrations in SD rats, sham animals and in rats with heart failure. ^[1] In conscious dogs with myocardial infarction (MI-sHF), Omecamtiv mecarbil leads to a significant increase in wall thickening (25%), stroke volume (44%), cardiac output (22%) and left ventricular (LV) systolic ejection time (26%). In addition, Omecamtiv mecarbil also results in the decreases of some hemodynamic parameters including heart rate, mean left atrial pressure, and LV end-diastolic pressure. In conscious dogs with left ventricular hypertrophy (LVH-sHF), Omecamtiv mecarbil leads to similar and not statistically different effects on hemodynamic parameters. ^[2]
• Clinical Trials: Omecamtiv mecarbil is currently in Phase II clinical trials in patients with Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure.

Protocol

• Protocol: Kinase Assay ^[1]
• Biochemical assays: Cardiac S1 myosin and thin filament proteins (actin, troponin complex, and tropomyosin) are prepared from bovine heart or rabbit skeletal muscle. Smooth muscle myosin is prepared from chicken gizzard. ATPase assays are performed in a kinetic fashion using NADH coupled enzyme system at pCa^2+ = 6.75. Rates are normalized to a DMSO control.
• Protocol: Animal Study ^[1]
• Animal Models: Sprague Dawley rats.
• Formulation: Omecamtiv mecarbil is dissolved in DMSO and then diluted in water.
• Doses: ≤1.2 mg/kg/hour
• Administration: Administered via i.v.

References

• References: [1] Anderson RL, et al. Mol Bio Cell, 2005, 16 (Abstract #1728).
• References: [2] Shen YT, et al. Circ Heart Fail. 2010, 3(4), 522-577.

REFERENCES

• Anderson RL, et al. Mol Bio Cell, 2005, 16 (Abstract #1728).
• Shen YT, et al. Circ Heart Fail. 2010, 3(4), 522-577.