942224-53-5

Upstream product

• 50606-31-0 methyl piperazine-1-carboxylate 
• 873697-69-9 C₇H₆FNO 
• 943732-45-4 C₇H₇FN₂ 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 96516-29-9 2-fluoro-3-nitrobenzaldehyde 

Downstream Products

• 873697-71-3 methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate 

Relevant academic research and scientific papers

Pharmacokinetics, disposition, and biotransformation of [14C]omecamtiv mecarbil in healthy male subjects after a single intravenous or oral dose

Omecamtiv mecarbil (OM) is a novel cardiac myosin activator that is currently in clinical development for the treatment of heart failure. The absorption and disposition of [14C]OM (60 μCi) were studied after a single intravenous infusion (35 mg over 1 hour) or oral solution dose (35 mg) in 14 healthy male subjects. Mean recovery of the administered [14C]OM dose was 85.1% and 86.5% over 336 hours for the intravenous and oral routes, respectively. After intravenous dosing, 47.8% and 37.3% of the dose was recovered in urine and feces, respectively; after oral dosing, 48.6% and 38.0% was recovered in urine and feces, respectively. Unchanged OM accounted for a minor percentage of radioactivity in urine (mean 7.7% of dose) and feces (mean 4.1% of dose) across all subjects. The major metabolites recovered in urine and feces were M3 (decarbamoylation product) and sequential metabolite M4 (lactam of M3), which accounted for means of 26.5% and 11.6% of the administered dose, respectively. The CYP4 family of enzymes was primarily responsible for the formation of M3 based on in vitro studies. Other metabolic pathways accounted for 14.9% of the administered dose. In pooled plasma, OM, M3, and M4 accounted for 83.8%, 6.0%, and 3.3% of the total [14C]OM-related materials. No other plasma metabolites constituted more than 3% of the administered dose. The bioavailability for OM solution was 93.5% after rapid and extensive absorption. SIGNIFICANCE STATEMENT This study characterized the absorption and disposition of OM, a novel small molecule being developed for the treatment of heart failure. OM was primarily cleared through metabolism by the CYP4 family through oxidative cleavage of a terminal carbamate moiety that resembles hydrolysis.

Compounds, compositions and methods

Certain substituted urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.