Riociguat

Bezeichnung:Riociguat

CAS-Nr625115-55-1

Englisch Name:Riociguat

CBNumberCB62473752

SummenformelC20H19FN8O2

Molgewicht422.42

MOL-Datei625115-55-1.mol

Riociguat physikalisch-chemischer Eigenschaften

Schmelzpunkt	247-251°C (dec.)
Siedepunkt	567.2±50.0 °C(Predicted)
Dichte	1.51
storage temp.	Refrigerator
Löslichkeit	DMSO (Slightly, Heated), Methanol (Slightly, Heated)
pka	1.51±0.50(Predicted)
Aggregatzustand	Solid
Farbe	Off-White to Orange
InChI	InChI=1S/C20H19FN8O2/c1-28(20(30)31-2)15-16(22)25-18(26-17(15)23)14-12-7-5-9-24-19(12)29(27-14)10-11-6-3-4-8-13(11)21/h3-9H,10H2,1-2H3,(H4,22,23,25,26)
InChIKey	WXXSNCNJFUAIDG-UHFFFAOYSA-N
SMILES	C(OC)(=O)N(C1=C(N)N=C(C2C3=CC=CN=C3N(CC3=CC=CC=C3F)N=2)N=C1N)C

Gefahreninformationscode (GHS)

Riociguat Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Chemische Eigenschaften
Brownish Orange Solid
Originator
Bayer (Germany)
Verwenden
Riociguat is used in the treatment for pulmonary hypertension.
Verwenden
Riocguat is used in the treatment for pulmonary hypertension.
Definition
ChEBI: A carbamate ester that is the methyl ester of {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamic acid. It is used for treatment of chronic thromboembolic pulmonary hypertension an pulmonary arterial hypertension
Trademarks
Adempas
Clinical Use
Guanylate cyclase stimulator:
Treatment of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH)
Synthese
The sequence began with condensation of commercial 2-fluorobenzylhydrazine (136) with sodium ethyl cyanopyruvate (137), which derives from diethyl oxalate to generate aminopyrazole 138. This was followed by the cyclocondensation with 3-dimethylaminoacrolein (139) to access pyrazolopyridine 140 in 50% yield for the two-step operation. Next, ester 140 was transformed to the corresponding primary amide 141, which was subsequently dehydrated upon treatment with trifluoroacetic acid anhydride (TFAA) to construct nitrile 142 in quantitative yield from 140. Subjection of cyanopyrazole 142 to Pinner conditions using methoxide and ammonium chloride in refluxing acetic acid generated amidine 143, and this was followed by condensation with the malononitrile derivative 144 in base to provide pyrimidine 145 in 73% yield. Hydrogenative cleavage of the phenyldiazine converted 145 to the pyrimidyl triamine 146, which underwent carbamoylation at the 40 position to produce the penultimate carbamate 147. This carbamate was then selectively methylated through deprotonation of the carbamate N¨CH proton followed by quench with methyl iodide. Sequential recrystallization from warm DMSO and refluxing ethyl acetate produced riociguat (XIX) in 64% yield from 147.
Arzneimittelwechselwirkung
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.
Stoffwechsel
N-demethylation, catalysed by CYP1A1, CYP3A4, CYP2C8 and CYP2J2 is the major biotransformation pathway leading to its major circulating active metabolite M-1 (pharmacological activity: 1/10th to 1/3rd of riociguat) which is further metabolised to the pharmacologically inactive N-glucuronide.
Riociguat and metabolites are excreted via both renal (33-45%) and biliary/faecal routes (48-59%). Approximately 9-44% of the administered dose was found as unchanged riociguat in faeces.

Riociguat Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Send Inquriy