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GT Biologics obtains FDA orphan drug designation for paediatric Crohn’s drug
GT Biologics, a developer of live biotherapeutics for the treatment of autoimmune diseases, has received orphan drug designation from the US Food and Drug Administration (FDA) for its lead product candidate, Thetanix.
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Bacteroides thetaiotaomicron
http://microbewiki.kenyon.edu/index.php/Bacteroides_thetaiotaomicron
Chelsea Therapeutics Announces FDA Advisory Committee to Review Northera(Droxidropa, 23651-95-8)
droxidropa
CHARLOTTE, N.C., Oct. 9, 2013 (GLOBE NEWSWIRE) — Chelsea Therapeutics International, Ltd. today announced that the U.S. Food and Drug Administration (FDA) has notified the Company that the New Drug Application (NDA) seeking approval to market Northera (droxidopa), an orally active synthetic precursor of norepinephrine, for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) will be reviewed by the Cardiovascular and Renal Drug Advisory Committee (CRDAC). The meeting is tentatively scheduled for January 14, 2014 read more here————
http://www.drugs.com/nda/northera_131009.html
old article cut paste
FDA Deems Resubmission a Complete Response; PDUFA Date Set as
February 14, 2014
CHARLOTTE, N.C., Sept. 4, 2013 (GLOBE NEWSWIRE) — Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today announced that the U.S. Food and Drug Administration (FDA) has acknowledged receipt of the New Drug Application (NDA) resubmission seeking approval to market NORTHERA(TM) (droxidopa), an orally active synthetic precursor of norepinephrine
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http://www.pharmalive.com/chelsea-therapeutics-announces-fda-acceptance-of-northera-nda-resubmission
L-DOPS (L-threo-dihydroxyphenylserine; Droxidopa; SM-5688) is a psychoactive drug and synthetic amino acid precursor which acts as a prodrug to the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline).[1] Unlike norepinephrine and epinephrine themselves, L-DOPS is capable of crossing the protective blood–brain barrier (BBB).[1]
Neurogenic orthostatic hypotension (NOH),[2] as well as NOH associated with multiple system atrophy (MSA), familial amyloid polyneuropathy (FAP), pure autonomic failure (PAF), and Parkinson’s disease (PD).
Intradialytic hypotension (IDH) or hemodialysis-induced hypotension.
Hypotension associated with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS).[3]
History
L-DOPS was developed by Sumitomo Pharmaceuticals under the trade name Droxidopa for the treatment of hypotension, including NOH,[2] and NOH associated with various disorders such as MSA, FAP, and PD, as well as IDH. The drug has been used in Japan and some surrounding Asian areas for these indications since 1989. Following a merge with Dainippon Pharmaceuticals in 2006, Dainippon Sumitomo Pharma licensed L-DOPS to Chelsea Therapeutics to develop and market it worldwide except in Japan, Korea, China, and Taiwan.
Clinical trials
Though L-DOPS has been used in Japan and Southeast Asia already for some time, it is also currently in clinical trials at the phase III point in the United States (U.S.), Canada, Australia, and throughout Europe. Provided L-DOPS successfully completes clinical trials, it could be approved for the treatment of NOH as early as 2011.[4] Additionally, phase II clinical trials for IDH are also underway. Chelsea Therapeutics obtained orphan drug status (ODS) for L-DOPS in the U.S. for NOH, and that of which associated with PD, PAF, and MSA, and is the pharmaceutical company developing it in that country.
- Goldstein, DS (2006). “L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug”. Cardiovasc Drug Rev 24 (3-4): 189–203. doi:10.1111/j.1527-3466.2006.00189.x. PMID 17214596.
- Mathias, Christopher J (2008). “L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension”. Clin Auton Res 18 (Supplement 1): 25–29.doi:10.1007/s10286-007-1005-z.
- Crofford, LJ (2008). “Pain management in fibromyalgia”. Curr Opin Rheumatol 20 (3): 246–250. doi:10.1097/BOR.0b013e3282fb0268. PMID 18388513.
- Search of: “Droxidopa” – List Results – ClinicalTrials.gov
- Robertson, David (2008). “The pathophysiology and diagnosis of orthostatic hypotension”. Clin Auton Res 18 (Supplement 1): 2–7. doi:10.1007/s10286-007-1004-0.
Adempas, first-in-class drug, approved by the FDA for the treatment of severe form of Pulmonary Artery Hypertension
October 09 ,2013 | By Márcio Barra
Adempas (riociguat), a first-in-class oral soluble guanylate cyclase stimulator from Bayer, has been approved today by the FDA for the treatment of Pulmonary Artery Hypertension (PAH) and as the first approved treatment for Chronic ThromboEmbolic Pulmonary Hypertension (CTEPH).
“Adempas is the first in its drug class approved to treat pulmonary hypertension and the first drug of any class to be shown to be effective for patients with CTEPH,” said Norman Stockbridge, director of the Division of Cardiovascular and Renal Drug Products in the FDA’s Center for Drug Evaluation and Research.
The drug, reviewed under the FDA’s 6 months priority review program, is noteworthy as it is the first approved treatment for chronic thromboembolic pulmonary hypertension, a more severe subset of pulmonary hypertension characterized by blockage of large pulmonary arteries by acute and recurrent pulmonary emboli, and organisation of these blood clots, which affects between…
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BAYER- sPRM (BAY 1002670) Vilaprisan is a novel oral progesterone receptor modulator that holds the promises of long-term treatment of patients with symptomatic uterine fibroids
http://www.who.int/medicines/publications/druginformation/issues/Proposed-List_109.pdf str is available in this link
20,20,21,21,21-pentafluoro-17-hydroxy-11β-[4-
(methanesulfonyl)phenyl]-19-nor-17α-pregna-4,9-dien-3-one
progesterone receptor antagonist
BAY 1002670, vilaprisan
1262108-14-4
C27H29F5O4S, 544.574
http://www.who.int/medicines/publications/druginformation/issues/Proposed-List_109.pdf str is available in this link
Bayer has also made good progress in the development of new treatment options for patients with gynecological diseases: sPRM (BAY 1002670) is a novel oral progesterone receptor modulator that holds the promises of long-term treatment of patients with symptomatic uterine fibroids. Based on promising early clinical data the initiation of a Phase III study is planned for mid-2014.
A selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor. A characteristic that distinguishes such substances from receptor full agonists (such as progesterone) and full antagonists (such as mifepristone) is that their action differs in different tissues (agonist in some while antagonist in others). This mixed agonist/antagonist profile of action leads to selective stimulation or inhibition progesterone-like action in different tissues and furthermore raises the possibility of dissociation of desirable therapeutic effects from undesirable side effects in synthetic progesterone receptor drug candidates
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Molidustat (BAY 85-3934), Bayer’s drug under initiation in patients with anemia associated with chronic kidney disease and/or end-stage renal disease.
Molidustat
UNII-9JH486CZ13, cas no 1154028-82-6, MW: 314.3076
2-(6-morpholin-4-ylpyrimidin-4-yl)-4-(triazol-1-yl)-1H-pyrazol-3-one
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors
For the cardio-renal syndrome, a Phase IIb program with the investigational new drug Molidustat (BAY 85-3934) is under initiation in patients with anemia associated with chronic kidney disease and/or end-stage renal disease. Molidustat is a novel inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) which stimulates erythropoietin (EPO) production and the formation of red blood cells. Phase I data have shown that inhibition of HIF-PH by Molidustat results in an increase in endogenous production of EPO.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.6 billion (2012), is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare’s aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 54,900 employees (Dec 31, 2012) and is represented in more than 100 countries. More information at www.healthcare.bayer.com.
molidustat
…………………………………………………………..
molidusat sodium
Sodium 1-[6-(morpholin-4-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-olate
Molidustat sodium is an orally-available hypoxia-inducible factor prolyl hydroxylase inhibitor in phase I clinical trials at Bayer for the treatment of patients suffering from renal anemia due to chronic kidney disease.
WO 2008067871
WO 2012065967
WO 2013167552
…………………………
2-Heteroaryl-4-aryl-1,2-dihydropyrazolones having a bactericidal and/or fungicidal action are disclosed in EP 165 448 and EP 212 281. The use of 2-heteroaryl-4-aryl-1,2-dihydropyrazolones as lipoxygenase inhibitors for treatment of respiratory tract, cardiovascular and inflammatory diseases is claimed in EP 183 159. 2,4-Diphenyl-1,2-dihydropyrazolones having a herbicidal activity are described in DE 2 651 008.
The preparation and pharmacological properties of certain 2-pyridyl-1,2-dihydropyrazolones are reported in Helv. Chim. Acta 49 (1), 272-280 (1966). WO 96/12706, WO 00/51989 and WO 03/074550 claim compounds having a dihydropyrazolone partial structure for treatment of various diseases, and hydroxy- or alkoxy-substituted bipyrazoles for treatment of neuropsychiatric diseases are disclosed in WO 2006/101903.
Heteroaryl-substituted pyrazole derivatives for treatment of pain and various CNS diseases are furthermore described in WO 03/051833 and WO 2004/089303. WO 2006/114213 has meanwhile disclosed 2,4-dipyridyl-1,2-dihydropyrazolones as inhibitors of HIF prolyl 4-hydroxylases.
The x-ray crystal structure of the compound 3-methyl-1-(pyridin-2-yl)-4-(1-pyridin-2-yl-3-methyl-1H-pyrazol-5-yl)-2H-3-pyrazolin-5 (114)-one (other name: 5,5′-dimethyl-2,2′-di-pyridin-2-yl-1′,2′-dihydro-2H,3′H-3,4′-bipyrazol-3′-one) is reported inActa Crystallogr., Section E: Structure Reports Oμline E57 (11), o1126-o1127 (2001) [Chem. Abstr. 2001:796190].
The synthesis of certain 3′,5-dimethyl-2-phenyl-1′-(1,3-thiazol-2-yl)-1′H,2H-3,4′-bipyrazol-5′-ol derivatives is described inIndian J. Heterocyclic Chem. 3 (1), 5-8 (1993) [Chem. Abstr. 1994:323362].
The preparation and tautomerism of individual 4-(pyrazol-5-yl)-pyrazolin-5-one derivatives is reported in J. Heterocyclic Chem. 27 (4), 865-870 (1990) [Chem. Abstr. 1991:428557]. A therapeutic use has not hitherto been described for the compounds mentioned in these publications. The compound 2-tert-butyl-1′-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-3′,5-dimethyl-1′H,2H-3,4′-bipyrazol-5′-ol is listed as a test example in WO 2007/008541.
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https://www.google.co.in/patents/US20100305085
Example 3A 3-(Dimethylamino)-2-(1H-1,2,3-triazol-1-yl)acrylic acid ethyl ester
The preparation of the starting compound is carried out analogously to 2A starting from 1.00 g (6.45 mmol) 2-(1H-1,2,3-triazol-1-yl)acetic acid ethyl ester.
Yield: 1.4 g (100% of th.)
1H-NMR (400 MHz, DMSO-d6): δ=8.10 (d, 1H), 7.78 (d, 1H), 7.65 (s, 1H), 4.03 (q, 2H), 3.06 (br. s, 3H), 2.10 (br. s, 3H), 1.12 (t, 3H).
LC-MS (Method 5): Rt=1.40 min; MS (ESIpos): m/z=211 [M+H]+.
Example 16A 4-(6-Hydrazinopyrimidin-4-yl)morpholine
Stage a): 4-(6-Chloropyrimidin-4-yl)morpholine
45.0 g (302.1 mmol) 4,6-dichloropyrimidine are initially introduced into 450 ml water. 26.3 g (302.1 mmol) morpholine are added and the mixture is stirred at 90° C. for 16 h. Thereafter, it is cooled to 0° C. and the precipitate formed is filtered off. The precipitate is washed once with 50 ml water and dried in air.
Yield: 51.0 g (85% of th.)
LC-MS (Method 4): Rt=1.09 min; MS (ESIpos): m/z=200 [M+H]+;
1H-NMR (400 MHz, DMSO-d6): δ=8.35 (s, 1H), 6.95 (s, 1H), 3.62 (s, 8H).
Stage b) 4-(6-Hydrazinopyrimidin-4-yl)morpholine
53.0 g (2.7 mmol) 4-(6-chloropyrimidin-4-yl)morpholine are initially introduced into 260 ml ethanol. 132.9 g (2.7 mol) hydrazine hydrate are added and the mixture is stirred under reflux for 16 h. Thereafter, it is cooled to RT and approx. half of the solvent is removed by distillation. The mixture is cooled to 0° C. and the solid formed is filtered off. It is rinsed with cold ethanol and the solid is dried first in air and then in vacuo.
Yield: 35.0 g (68% of th.)
LC-MS (Method 1): Rt=0.17 min; MS (ESIpos): m/z=196 [M+H]+;
1H-NMR (400 MHz, DMSO-d6): δ=7.94 (s, 1H), 7.70 (s, 1H), 5.91 (s, 1H), 4.15 (s, 2H), 3.66-3.60 (m, 4H), 3.45-3.37 (m, 4H).
Example 71 2-(6-Morpholin-4-ylpyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one
1.9 g (8.8 mmol) of the compound from Example 3A and 1.9 g (9.7 mmol) of the compound from Example 16A are initially introduced into 25 ml ethyl acetate and 504 mg (4.4 mmol) TFA are added at RT. The mixture is stirred under reflux for 16 h, then cooled to 5° C. and subsequently stirred for a further 2 h. The solid formed is filtered off, washed with ethyl acetate and dried first in air and thereafter under a high vacuum. 1.7 g of product are obtained.
The mother liquor is combined with the wash solution and the solvent is removed. According to LC-MS, the residue (2.4 g) still contains the intermediate 3-[2-(6-morpholin-4-ylpyrimidin-4-yl)hydrazino]-2-(1H-1,2,3-triazol-1-yl)prop-2-enoic acid ethyl ester (intermediate stage of the cyclization), which is used directly for the preparation of Example 72 (see there).
Yield: 1.7 g (61% of th.)
LC-MS (Method 9): Rt=0.90 min; MS (ESIpos): m/z=315 [M+H]+;
1H-NMR (400 MHz, DMSO-d6): δ=8.42 (s, 1H), 8.38 (s, 1H), 8.01 (s, 1H), 7.73 (s, 1H), 7.70 (s, 1H), 3.71-3.65 (m, 4H), 3.57-3.51 (m, 4H).
hydrochloride
Example 72 2-(6-Morpholin-4-ylpyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one hydrochloride
Batch 1: 7.5 ml of a 4 N solution of hydrogen chloride in dioxane are added to 1.7 g (5.4 mmol) of the compound from Example 71. The mixture is stirred at RT, 5 ml dioxane are added and the mixture is stirred at RT for 16 h. The solid is filtered off and washed with 5 ml dioxane. The mixture is dried under a high vacuum for 16 h, 10 ml methanol are then added and the mixture is stirred at RT for 1 h. The solid is filtered off, washed with 4 ml methanol and dried under a high vacuum. 1.6 g of the title compound are obtained.
Batch 2: A further amount of the title compound is obtained as follows: The residue (2.4 g) obtained from the mother liquor during the synthesis of Example Compound 71, which contains the open-ring intermediate state of the cyclization, 3-[2-(6-morpholin-4-ylpyrimidin-4-yl)hydrazino]-2-(1H-1,2,3-triazol-1-yl)prop-2-enoic acid ethyl ester, is dissolved in 12 ml ethanol and 1.5 ml 30% strength sodium methylate solution in methanol are added at RT, while stirring. The mixture is subsequently stirred at RT for 45 min, then adjusted to pH 5 with 2 N hydrochloric acid and subsequently stirred at RT for a further 16 h. The mixture is cooled to 10° C. and the solid is filtered off and washed with 3.5 ml dioxane. The mixture is dried under a high vacuum for 16 h, 5 ml methanol are then added and the mixture is subsequently stirred at RT for 1 h. The solid is filtered off, washed with 2 ml methanol and dried under a high vacuum to give a further 997 mg of the title compound in this way.
Yield: together 2.6 g (83% of th.)
LC-MS (Method 6): Rt=0.89 min; MS (ESIpos): m/z=315 [M+H]+;
1H-NMR (400 MHz, DMSO-d6): δ=8.54 (s, 1H), 8.39 (s, 1H), 8.28 (s, 1H), 7.88 (s, 1H), 7.42 (s, 1H), 3.71 (s, 8H).
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Copanlisib (BAY 80-6946), Bayer’s novel, oral phosphatidylinositol-3 kinases (PI3K) inhibitor
Copanlisib (BAY 80-6946)
1032568-63-0, cas no
MW: 480.5262
In oncology, Copanlisib (BAY 80-6946), a novel, oral phosphatidylinositol-3 kinases (PI3K) inhibitor, was selected for accelerated development. Copanlisib demonstrated a broad anti-tumor spectrum in preclinical tumor models and promising early clinical signals in a Phase I study in patients with follicular lymphoma. A Phase II study in patients with Non-Hodgkin’s lymphoma is currently ongoing.
PI3K inhibitor BAY 80-6946
A phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor BAY 80-6946 inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
Finerenone (BAY 94-8862), BAYER’S next generation oral, non-steroidal Mineralocorticoid Receptor antagonist which blocks the deleterious effects of aldosterone
CAS Number: 1050477-31-0, UNII-DE2O63YV8R
MW: 378.4298, C21-H22-N4-O3
Finerenone (BAY 94-8862) is a next generation oral, non-steroidal Mineralocorticoid Receptor antagonist which blocks the deleterious effects of aldosterone.
Currently available steroidal MR antagonists have proven to be effective in reducing cardiovascular mortality in patients with heart failure but have significant side effects that limit their utilization.
Finerenone is currently in clinical Phase IIb development for the treatment of worsening chronic heart failure, as well as diabetic nephropathy.
Glaxo Plans to File for Malaria Vaccine Approval Next Year
Malaria vaccine candidate reduces disease over 18 months of follow-up in late-stage study of more than 15,000 infants and young children
Malaria is a significant public health burden, claiming 660,000 lives a year – mostly children in sub-Saharan Africa
-Data support plan to submit regulatory application in 2014
Multilateral Initiative on Malaria Pan African Conference, Durban, South Africa — Results from a large-scale Phase III trial, presented today in Durban, show that the most clinically advanced malaria vaccine candidate, RTS,S, continued to protect young children and infants from clinical malaria up to 18 months after vaccination. Based on these data, GSK now intends to submit, in 2014, a regulatory application to the European Medicines Agency (EMA). The World Health Organization (WHO) has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015 if it is granted a positive scientific opinion by EMA.
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http://www.pharmalive.com/glaxo-plans-to-file-for-malaria-vaccine-approval-next-year
The U.S. Food and Drug Administration approved Adempas (riociguat) to treat adults with two forms of pulmonary hypertension.
October 8, 2013 — The U.S. Food and Drug Administration today approved Adempas (riociguat) to treat adults with two forms of pulmonary hypertension.
Pulmonary hypertension is caused by abnormally high blood pressure in the arteries of the lungs. It makes the right side of the heart work harder than normal. In its various forms, pulmonary hypertension is a chronic, progressive, debilitating disease, often leading to death or need for lung transplantation
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http://www.drugs.com/newdrugs/fda-approves-adempas-pulmonary-hypertension-3927.html
In the area of pulmonary hypertension Adempas (Riociguat) is the first member of a novel class of compounds – so-called ‘soluble guanylate cyclase (sGC) stimulators’ – being investigated as a new and specific approach to treating different types of pulmonary hypertension (PH). Adempas has the potential to overcome a number of limitations of currently approved treatments for pulmonary arterial hypertension (PAH) and addresses the unmet medical need in patients with chronic thromboembolic pulmonary hypertension (CTEPH). It was approved for the treatment of CTEPH in Canada in September 2013, making it the world’s first drug approved in this deadly disease.
Riociguat has already shown promise as a potential treatment option beyond these two PH indications. An early clinical study was conducted in PH-ILD (interstitial lung disease), a disease characterized by lung tissue scarring (fibrosis) or lung inflammation which can lead to pulmonary hypertension, and, based on positive data, the decision was taken to initiate Phase IIb studies in PH-IIP (idiopathic pulmonary fibrosis), a subgroup of PH-ILD. Moreover, scientific evidence was demonstrated in preclinical models that the activity may even go beyond vascular relaxation. To prove the hypothesis Bayer is initiating clinical studies in the indication of systemic sclerosis (SSc), an orphan chronic autoimmune disease of the connective tissue affecting several organs and associated with high morbidity and mortality. If successful, Riociguat has the potential to become the first approved treatment for this devastating disease.
synthesis
Generic Name: Riociguat
Trade Name: Adempas
Synonym: BAY 63-2521
CAS number: 625115-55-1
Chemical Name: Methyl N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methyl-carbaminate
Mechanism of Action: soluble guanylyl cyclase (sGC) stimulator
Date of Approval: October 8, 2013(US)
Indication: Pulmonary Hypertension
Company: Bayer AG
1)J. Mittendorf.; S. Weigand.; C. Alonso-Alija.; E. Bischoff.; A. Feurer.; M. Gerisch.; A. Kern.; A. Knorr.; D. Lang.; K. Muenter.; M. Radtke.; H. Schirok.; K.-H. Schlemmer.; E. Stahl.; A. Straub.; F. Wunder.; J.-P. Stasch. Discovery of Riociguat (BAY 63-2521): A Potent, Oral Stimulator of Soluble Guanylate Cyclase for the Treatment of Pulmonary Hypertension, ChemMedChem. 2009, 4, 853-865.
2)Cristina Alonso-Alija, Bayer Ag, Erwin Bischoff, Achim Feurer, Klaus Muenter, Elke Stahl, Johannes-Peter Stasch, Stefan Weigand, Carbamate-substituted pyrazolopyridines, WO2003095451 A1
3)Franz-Josef Mais, Joachim Rehse, Winfried Joentgen, Konrad SIEGEL, Process for preparing methyl methylcarbamate and its purification for use as pharmaceutically active compound,US20110130410
4)Claudia Hirth-Dietrich, Peter Sandner, Johannes-Peter Stasch, Andreas Knorr, Degenfeld Georges Von, Michael Hahn, Markus Follmann, The use of sGC stimulators, sGC activators, alone and combinations with PDE5 inhibitors for the treatment of systemic sclerosis (SSc), WO 2011147810A1
5)Li Liang, Li Xing-zhou, Liu Ya-dan, Zheng Zhi-bing, Li Song, Synthesis of riociguat in treatment of pulmonary hypertension, Chinese Journal of Medicinal Chemistry(Zhongguo Yaowu Huaxue Zazhi), 21(2),120-125; 2011
Jens Ackerstaff, Lars BÄRFACKER, Markus Follmann, Nils Griebenow, Andreas Knorr, Volkhart Min-Jian Li, Gorden Redlich, Johannes-Peter Stasch, Stefan Weigand, Frank Wunder, Bicyclic aza heterocycles, and use thereof, WO2012028647 A1
2)Claudia Hirth-Dietrich, Peter Sandner, Johannes-Peter Stasch, Andreas Knorr, Degenfeld Georges Von, Michael Hahn, Markus Follmann, The use of sGC stimulators, sGC activators, alone and combinations with PDE5 inhibitors for the treatment of systemic sclerosis (SSc), WO 2011147810A1
Jin Li, Xiaoyu Yang, Jingwei ZHU, Minmin Yang, Xihan Wu, Method for synthesizing 1-(2-fluorobenzyl)-1H -pyrazolo[3,4-b]pyridin -3-formamidine hydrochloride, WO2013086935 A1
veerareddy Arava, Surendrareddy Gogireddy, An expeditious synthesis of riociguat, A pulmonary hypertension drug, Der Pharma Chemica, 2013, 5(4):232-239
cut paste from my earlier post
RIOCIQUAT
CAS NO 625115-55-1
Methyl N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methyl-carbaminate
9 APRIL2013
Bayer has been boosted by the news that regulators in the USA are fast-tracking the German group’s investigational pulmonary arterial hypertension riociguat.
The US Food and Drug Administration has granted priority review to the New Drug Application for riociguat, which Bayer filed in February on both sides of the Atlantic for PAH and a related condition, inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The FDA bestows a priority review on medicines that offer major advances in care or that provide a treatment where no adequate therapy exists. The agency aims to complete its assessment within eight months from the submission of the NDA, rather than the standard 12 months.
Riociguat (BAY 63-2521) is a novel drug that is currently in clinical development by Bayer. It is a stimulator of soluble guanylate cyclase (sGC). At the moment Phase III clinical trialsinvestigate the use of riociguat as a new approach to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) andpulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of a novel class of sGC stimulators
The submissions are based on two Phase III studies and riociguat, the first member of a novel class of compounds called stimulators of soluble guanylate cyclase (sGC), met its primary endpoint in both trials, a change in exercise capacity after 12- or 16 weeks respectively. The drug was generally well tolerated, with a good safety profile.
If approved, riociguat would be going up against Actelion’s Tracleer (bosentan) and Gilead Sciences/GlaxoSmithKline’s Letairis/Volibris (ambrisentan). Actelion, which has dominated the PAH market, has already filed its follow-up to Tracleer, Opsumit (macitentan).
Últimas tendencias: Tanezumab
Los resultados del estudio fase III publicados recientemente en Arthritis and rheumatism muestran que tanezumab, un nuevo biológico, produce un efecto analgésico y mejora la función física en pacientes con osteoartritis de la cadera.
Tanezumab actúa a través del factor de crecimiento nervioso, deteniendo la transmisión neuronal de señales de dolor muscular y óseo al cerebro, por lo tanto ofrece una oportunidad para aliviar el dolor.
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DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 