ChemicalBook
Chinese Japanese Germany Korea

Riociguat

Pharmacological effects Clinical evaluation Production Method Patent cases
Riociguat
Riociguat structure
CAS No.
625115-55-1
Chemical Name:
Riociguat
Synonyms
CS-718;Riocguat;riocigua;Riociguat;Riociguatr;Bay 63-2521;Riociguat USP/EP/BP;Riociguat IMpurtiy D;Bay63-2521,Riociguat;Riociguat, BZY 632521
CBNumber:
CB62473752
Molecular Formula:
C20H19FN8O2
Formula Weight:
422.42
MOL File:
625115-55-1.mol

Riociguat Properties

Boiling point:
567.2±50.0 °C(Predicted)
Density 
1.51
pka
1.51±0.50(Predicted)
FDA UNII
RU3FE2Y4XI
ATC code
C02KX05

Riociguat price More Price(38)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 9000554 Riociguat ≥98% 625115-55-1 5mg $68 2021-12-16 Buy
Cayman Chemical 9000554 Riociguat ≥98% 625115-55-1 10mg $129 2021-12-16 Buy
TRC R520000 Riociguat 625115-55-1 10mg $150 2021-12-16 Buy
Biosynth Carbosynth FD43240 N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methylcarbamic acid methyl ester 625115-55-1 500 mg $250 2021-12-16 Buy
ChemScene CS-0584 Riociguat 99.58% 625115-55-1 50mg $288 2021-12-16 Buy

Riociguat Chemical Properties,Uses,Production

Pharmacological effects

Riociguat is a soluble guanylyl cyclase activator, developed by the German Bayer ,it is an important signaling enzyme, which can be activated by nitric oxide (NO) to catalyze guanosine triphosphate ( GTP) to convert into the second messenger cyclic guanosine monophosphate (cGMP). Soluble guanylate cyclase is currently the only known NO receptor. Damage of NO-sGC-cGMP signal pathway is believed to be the cause of the incidence of cardiovascular, lung, endothelium, kidney and liver diseases. NO synthesis in patients with pulmonary hypertension is not enough, NO donor drugs, although effective, short half-life, riociguat can directly activate sGC, stable NO-sGC combination so as to upregulate the second messenger cGMP. riociquat can significantly increase exercise tolerance in patients with hemodynamic parameters of cardiac function and prolong the time to reach clinical worsening (PATENT study), It may also be effective in treating CTEPH(CHEST study) .
October 8, 2013, the US FDA approved Riociguat for the treatment of chronic thromboembolic pulmonary hypertension and PAH (Pulmonary Arterial Hypertension).
At present, Riociguat is not yet sold in the domestic market ,in the United States it is sold by the Haoeyou Pharmacy , the pharmacy is subsidiary of California Healthcom Group, because the market ofRiociguat is in its infancy, its sales grow slowly.

Clinical evaluation

In clinical trials ,261 patients with chronic thromboembolic pulmonary hypertension (CTEPH) were divided into riociguat and placebo groups, a six-minute walk distance (6MWD) as the main clinical endpoint, after 16 weeks of treatment, 6MWD of riociguat group increased by 46 meters higher than the average in the placebo group. 443 cases of PAH were divided into riociguat and placebo groups,after 12 weeks of treatment, riociguat group increased 36 meters higher than the average 6MWD in the placebo group. Boxed warning suggests that the drug has a embryo toxicity, pregnant patients are forbidden.
Adempas is granted baseing on two global III studies CHEST-1 and PATENT-1, whose findings are published in the July 25, 2013"New England Journal of Medicine," (2013; 369: 330-40; 2013; 369: 319-29). Thomson Reuters released analysis report that it is expected that sales of the drug in 2017 will reach $ 679 million, while the market will face a potential threat constituted by the Swiss company Actelion bosentan and Gilead drug Imber bosentan tablets.
The above information is edited by the chemicalbook of Tian Ye.

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.
a chemical reactions road map of Riociguat production
Figure 1 is a chemical reactions road map of Riociguat production .

Patent cases

US7173037 (there is a deadline to April 25, 2023), US6743798 (valid until July 16, 2019).

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.

Chemical Properties

Brownish Orange Solid

Originator

Bayer (Germany)

Uses

Riociguat is used in the treatment for pulmonary hypertension.

Uses

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

brand name

Adempas

Chemical Synthesis

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–H proton followed by quench with methyl iodide. Sequential recrystallization from warm DMSO and refluxing ethyl acetate produced riociguat (XIX) in 64% yield from 147.

Riociguat Preparation Products And Raw materials

Raw materials

Preparation Products


Riociguat Suppliers

Global( 231)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
Hangzhou FandaChem Co.,Ltd.
008615858145714
+86-571-56059825 fandachem@gmail.com CHINA 9115 55
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26782 60
Lianyungang happen teng technology co., LTD
15950718863
wang666xt@163.com CHINA 296 58
career henan chemical co
+86-0371-55982848
sales@coreychem.com China 29954 58
Shanghai Arbor Chemical Co., Ltd.
021-60451682
021-60451683 act@arborchemical.com CHINA 906 58
Shenzhen Nexconn Pharmatechs Ltd
15013857715
admin@nexconn.com CHINA 3004 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 linda@hubeijusheng.com CHINA 28229 58
HubeiwidelychemicaltechnologyCo.,Ltd
18627774460
faith@widelychemical.com CHINA 743 58
Chongqing Chemdad Co., Ltd
+86-13650506873
sales@chemdad.com CHINA 37282 58

View Lastest Price from Riociguat manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-12-18 Riociguat
625115-55-1
US $0.00 / g 1g 98.0% 10kg/month WUHAN FORTUNA CHEMICAL CO., LTD
2021-11-27 Riociguat
625115-55-1
US $1.00 / g 100g 99.99% 5ton/Month Hebei Yirun Sega Biological Technology Co. Ltd
2021-11-08 Riociguat
625115-55-1
US $5.00 / KG 1KG 99% 20 Tons Wuhan wingroup Pharmaceutical Co., Ltd

625115-55-1(Riociguat)Related Search:


  • Riociguat
  • N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methylcarbamic acid methyl ester
  • Bay 63-2521
  • Carbamic acid, (4,6-diamino-2-(1-((2-fluorophenyl)methyl)-1H-pyrazolo(3,4-B)pyridin-3-yl)-5-pyrimidinyl)methyl-, methyl ester
  • Riociguat (BAY 63-2521)
  • Riocguat
  • CS-718
  • Riociguat, BZY 632521
  • BAY 63-2521; BAY 632521
  • Riociguat IMpurtiy D
  • methyl N-(4,6-diamino-2-{1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}pyrimidin-5-yl)-N-methylcarbamate
  • Bay63-2521,Riociguat
  • [4,6-DiaMino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyriMidin-5-yl]MethylcarbaMic acid Methyl ester
  • Methyl (4,6-diaMino-2-(1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)pyriMidin-5-yl)(Methyl)carbaMate
  • Riociguat N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methylcarbamic acid methyl ester
  • Carbamic acid, N-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methyl-, methyl ester
  • fondaparinux sodium intermediateA-8)
  • riocigua
  • Riociguat USP/EP/BP
  • Riociguatr
  • 625115-55-1
  • 615115-55-1
  • C20H19FN8O2
  • API
Copyright 2017 © ChemicalBook. All rights reserved