Chemical Property of Riociguat
Chemical Property:
- Boiling Point:567.202 °C at 760 mmHg
- PKA:1.51±0.50(Predicted)
- Flash Point:296.833 °C
- PSA：138.80000
- Density:1.513 g/cm3
- LogP:2.95400
- Storage Temp.:Refrigerator
- Solubility.:DMSO (Slightly, Heated), Methanol (Slightly, Heated)
- XLogP3:1.6
- Hydrogen Bond Donor Count:2
- Hydrogen Bond Acceptor Count:9
- Rotatable Bond Count:5
- Exact Mass:422.16150004
- Heavy Atom Count:31
- Complexity:618
- Purity/Quality:
-
99% *data from raw suppliers
Riociguat *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
- Drug Classes:Pulmonary Arterial Hypertension Agents
- Canonical SMILES:CN(C1=C(N=C(N=C1N)C2=NN(C3=C2C=CC=N3)CC4=CC=CC=C4F)N)C(=O)OC
- Recent ClinicalTrials:A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction
- Recent EU Clinical Trials:An open-label, prospective, single centre study of the effects of Riociguat on RIght VEntricular size and function in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension
- Recent NIPH Clinical Trials:Investigational Randomized Controlled Trial of Patients with Chronic Thromboembolic Pulmonary Hypertension treated with Riociguat vs Selexipag
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Production Method
Synthetic key of Riociguat is the synthesis of three heterocyclic ring. Compounds 1 and 2 directly close the pyrazole ring to generate 3,3 and 4 and then close the pyrazole ring to obtain5, ethyl of 5 is dehydrated using trifluoroacetic anhydride to give a cyano group after amidation by the ammonia , the cyano group is treated with methanol sodium and chloride ammonium to get amidine 6. The two nitrogen atoms on Amidine 6 as dinucleophile, with two cyano on compound 7 as the electrophile ,directly close the pyrimidine ring to give 8. pyrimidine 5-position amino group on 8 with a strong nucleophilic, directly reacts with methyl chloride and then methylates to give riociguat.
Figure 1 is a chemical reactions road map of Riociguat production .
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Description
In September 2013, Health Canada approved riociguat (also referred to as BAY 63-2521), for the treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) after surgical treatment or inoperable CTEPH and for the treatment of adults with pulmonary arterial hypertension (PAH). Riociguat has a dual mode of action and works by (a) sensitizing sGC to the body’s NO by stabilizing NO–sGC binding and (b) an NO-independent, direct stimulation of sGC via a different binding site. This process restores the NO–sGC–cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation.Headache, dizziness, dyspepsia/gastritis, nausea, diarrhea, hypotension, vomiting, anemia, gastroesophageal reflux, and constipation were the most common adverse events ( 3%) observed during riociguat clinical trials. Riociguat comes with a black box warning for embryo-fetal toxicity.
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Uses
Riocguat is used in the treatment for pulmonary hypertension. Riociguat is used in the treatment for pulmonary hypertension.
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Clinical Use
Guanylate cyclase stimulator:
Treatment of chronic thromboembolic pulmonary
hypertension (CTEPH) and pulmonary arterial
hypertension (PAH)
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Drug interactions
Potentially hazardous interactions with other drugs
Avanafil, sildenafil, tadalafil, vardenafil: enhanced
hypotensive effect - avoid.
Nicorandil: possibly enhanced hypotensive effect -
avoid.
Nitrates: possibly enhanced hypotensive effect -
avoid.
