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Details

Stereochemistry ACHIRAL
Molecular Formula C20H19FN8O2
Molecular Weight 422.4157
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RIOCIGUAT

SMILES

COC(=O)N(C)C1=C(N)N=C(N=C1N)C2=NN(CC3=CC=CC=C3F)C4=C2C=CC=N4

InChI

InChIKey=WXXSNCNJFUAIDG-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C20H19FN8O2
Molecular Weight 422.4157
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Riociguat is a potent, oral stimulator of soluble guanylate cyclase (sGC). It is the first member of a novel class of compounds, being developed by Bayer as an investigational, oral treatment to target a key molecular mechanism underlying pulmonary hypertension (PH). Riociguat demonstrated robust clinical efficacy in two separate PH indications: chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension(PAH). Riociguat works in two ways: it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding and directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation. Through this unique way of working, riociguat decreases blood pressure within the pulmonary arteries that take blood from the heart to the lungs, reducing pressure on the heart leading to improved patient outcomes.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ADEMPAS
Primary
ADEMPAS
PubMed

PubMed

TitleDatePubMed
Molecule of the month. Riociguat.
2009 Apr
Riociguat: an upcoming therapy in chronic thromboembolic pulmonary hypertension?
2010 Mar
[Pulmonary arterial hypertension--a rare form of pulmonary hypertension].
2010 May
Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study.
2010 Oct
Patents

Sample Use Guides

In Vivo Use Guide
The recommended starting dosage is 1 mg taken 3 times a day. For patients who may not tolerate the hypotensive effect of the drug, consider a starting dose of 0.5 mg taken three times a day. If systolic blood pressure remains greater than 95 mmHg and the patient has no signs or symptoms of hypotension, up-titrate the dose by 0.5 mg taken three times a day. Dose increases should be no sooner than 2 weeks apart. The dose can be increased to the highest tolerated dosage, up to a maximum of 2.5 mg taken three times a day. If at any time, the patient has symptoms of hypotension, decrease the dosage by 0.5 mg taken three times a day.
Route of Administration: Oral
In Vitro Use Guide
Human fetal airway smooth muscle (fASM) cells were derived from 18-20 weeks PCA fetuses. Hyperoxia effects were inhibited in the presence of riociguat, a sGC stimulator (50mg/ml, 24 h each).
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:44:04 UTC 2019
Edited
by admin
on Mon Oct 21 20:44:04 UTC 2019
Record UNII
RU3FE2Y4XI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RIOCIGUAT
DASH   INN   JAN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
RIOCIGUAT [WHO-DD]
Common Name English
BAY 63-2521
Code English
RIOCIGUAT [VANDF]
Common Name English
RIOCIGUAT [USAN]
Common Name English
RIOCIGUAT [MI]
Common Name English
RIOCIGUAT [JAN]
Common Name English
ADEMPAS
Brand Name English
METHYL N-(4,6-DIAMINO-2-(1-((2-FLUOROPHENYL)METHYL)-1H-PYRAZOLO(3,4-B)PYRIDIN-3-YL)PYRIMIDIN-5-YL)-N-METHYLCARBAMATE
Systematic Name English
BAY-63-2521
Code English
RIOCIGUAT [INN]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS ADEMPAS (AUTHORIZED: HYPERTENSION, PULMONARY)
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
NDF-RT N0000190485
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
FDA ORPHAN DRUG 406913
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
FDA ORPHAN DRUG 439514
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
FDA ORPHAN DRUG 392113
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
WHO-ATC C02KX05
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
EU-Orphan Drug EU/3/14/1299
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
NCI_THESAURUS C29707
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
Code System Code Type Description
EVMPD
SUB32880
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
NCI_THESAURUS
C152225
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
INN
8857
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
ChEMBL
CHEMBL2107834
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
NDF-RT
N0000190484
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY Guanylate Cyclase Stimulators [MoA]
PUBCHEM
11304743
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
JAPANESE REVIEW
ADEMPAS
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY APPROVED JANUARY 2014
CAS
625115-55-1
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
RXCUI
1439816
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY RxNorm
MERCK INDEX
M9628
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY Merck Index
IUPHAR
5257
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
DRUG BANK
DB08931
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
WIKIPEDIA
RIOCIGUAT
Created by admin on Mon Oct 21 20:44:05 UTC 2019 , Edited by admin on Mon Oct 21 20:44:05 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
TARGET -> AGONIST
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
Riociguat is mainly cleared by metabolism by CYP1A1, CYP3A, CYP2C8 and CYP2J2. Formation of the major active metabolite, M1, is catalyzed by CYP1A1, which is inducible by polycyclic aromatic hydrocarbons such as those present in cigarette smoke. Has one-tenth to one-third of the biological activity of riociguat.
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC