5th Generation Cephalosporins
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Showing posts with label New Drugs. Show all posts
Showing posts with label New Drugs. Show all posts
Sunday 8 September 2013
Sunday 1 September 2013
Pharmaceutical R&D and its impact on global health
FACTS AND FIGURES 2012 - IFPMA
www.ifpma.org/.../IFPMA_-_Facts_And_Figures_2012_LowResSingleP...
see pdf file at
Thursday 22 August 2013
Bayer's Stivarga sets second OK in Japan
regorafenib
Bayer chalked up another approval for blockbuster-in-waiting Stivarga after Japan gave a green light for the drug's use in gastrointestinal stromal tumour (GIST).
This is the second approval for Stivarga (regorafenib) in Japan, having been cleared for the treatment of advanced or recurrent colorectal cancer in March. The product has already been approved for both indications in the US and is under review for the colorectal cancer indication in Europe
Sunday 4 August 2013
Cinnamon's Infection and Diabetes-Fighting Properties Revealed
Cinnamon's medicinal potential is as rich and complex as its flavor and aroma, with blood sugar balancing and infection fighting top on the list.
Cinnamon is a familiar spice, but few are aware of just how diverse are its medicinal properties. TheUS National Library of Medicine houses well over 1300 abstracts on the subject of the various forms of cinnamon's potential health benefits.
Tuesday 30 July 2013
Study Shows Diets Lacking Omega-3s Lead to Anxiety, Hyperactivity in Teens
Pittsburgh, PA (Scicasts) – Diets lacking omega-3 fatty acids―found in foods like wild fish, eggs, and grass-fed livestock―can have worsened effects over consecutive generations, especially affecting teens, according to a University of Pittsburgh study.
read at
http://scicasts.com/bio/6358-study-shows-diets-lacking-omega-3s-lead-to-anxiety-hyperactivity-in-teens
amcrasto@gmail.com
Friday 26 July 2013
Why Vertex Earnings Prospects Are So Bright
Why Vertex Earnings Prospects Are So Bright
Motley Fool
With few drugs targeting cystic fibrosis and almost half of patients suffering from the particular mutation that the study targeted, Vertex could well have identified a blockbuster in the space. Moreover, with an ongoing phase 3 trial of another ...
http://www.fool.com/investing/general/2013/07/25/why-vertex-earnings-prospects-are-so-bright.aspx
Vertex Pharmaceuticals has a couple of approved drugs, including its Kalydeco cystic fibrosis drug and its Incivek treatment for hepatitis C. But it also has some promising prospects in the development stage. With the company having reported some positive study results during the quarter, Vertex saw its shares soar as more investors got aboard the biotech's bandwagon. Let's take an early look at what's been happening with Vertex Pharmaceuticals over the past quarter and what we're likely to see in its quarterly report
Motley Fool
With few drugs targeting cystic fibrosis and almost half of patients suffering from the particular mutation that the study targeted, Vertex could well have identified a blockbuster in the space. Moreover, with an ongoing phase 3 trial of another ...
http://www.fool.com/investing/general/2013/07/25/why-vertex-earnings-prospects-are-so-bright.aspx
Vertex Pharmaceuticals has a couple of approved drugs, including its Kalydeco cystic fibrosis drug and its Incivek treatment for hepatitis C. But it also has some promising prospects in the development stage. With the company having reported some positive study results during the quarter, Vertex saw its shares soar as more investors got aboard the biotech's bandwagon. Let's take an early look at what's been happening with Vertex Pharmaceuticals over the past quarter and what we're likely to see in its quarterly report
Tuesday 23 July 2013
Phase III prostate cancer trial for 'homing' injection shows improvements
Phase III prostate cancer trial for 'homing' injection shows improvements
A new treatment for advanced prostate cancer that homes-in on tumours to deliver a high-energy burst of radiation to cancer cells has shown significant benefits in a large scale clinical trial.
The trial of 921 patients showed that treatment with the radioactive Radium-223 gave men with late-stage prostate cancer an average extra of 15 weeks of life.http://www.pharmaceutical-technology.com/news/newsphase-iii-prostate-cancer-trial-for-homing-injection-shows-benefit?WT.mc_id=DN_News
Friday 19 July 2013
Alkermes Adds Multiple Sclerosis Pill To Expanding Pipeline
Alkermes Adds Multiple Sclerosis Pill To Expanding PipelineTheStreet.comThe company expects to seek permission from FDA to begin human testing of its MMF prodrugs for multiple sclerosis in 2014, with a phase I study slated to begin mid-year. Composition of matter patents have been filed, which if granted, would give the ...
read all at
http://www.thestreet.com/story/11981784/1/alkermes-adds-multiple-sclerosis-pill-to-expanding-pipeline.html?cm_ven=GOOGLEN
read all at
http://www.thestreet.com/story/11981784/1/alkermes-adds-multiple-sclerosis-pill-to-expanding-pipeline.html?cm_ven=GOOGLEN
Santarus Completes Patient Enrollment in CONTRIBUTE Study with UCERIS (budesonide) as Add-on Treatment to 5-ASA Drugs
Santarus Completes Patient Enrollment in CONTRIBUTE Study with UCERIS ...MarketWatchA Biologics License Application for RUCONEST for the treatment of acute angioedema attacks in patients with hereditary angioedema is under review by the U.S. Food and Drug Administration with a response expected in April 2014. Santarus is also ...
read all at
http://www.marketwatch.com/story/santarus-completes-patient-enrollment-in-contribute-study-with-uceris-budesonide-as-add-on-treatment-to-5-asa-drugs-2013-07-18
SAN DIEGO, Jul 18, 2013 (BUSINESS WIRE) -- Santarus, Inc. /quotes/zigman/91852/quotes/nls/snts SNTS -0.61% today announced the completion of enrollment in the CONTRIBUTE clinical study designed to evaluate the incremental benefit of adding UCERIS(R) (budesonide) extended release 9 mg tablets to oral aminosalicylate (5-ASA) therapy for the induction of clinical remission in adult patients with active, mild to moderate ulcerative colitis. UCERIS is currently approved in the U.S. for the induction of remission in patients with active, mild to moderate ulcerative colitis.
read all at
http://www.marketwatch.com/story/santarus-completes-patient-enrollment-in-contribute-study-with-uceris-budesonide-as-add-on-treatment-to-5-asa-drugs-2013-07-18
SAN DIEGO, Jul 18, 2013 (BUSINESS WIRE) -- Santarus, Inc. /quotes/zigman/91852/quotes/nls/snts SNTS -0.61% today announced the completion of enrollment in the CONTRIBUTE clinical study designed to evaluate the incremental benefit of adding UCERIS(R) (budesonide) extended release 9 mg tablets to oral aminosalicylate (5-ASA) therapy for the induction of clinical remission in adult patients with active, mild to moderate ulcerative colitis. UCERIS is currently approved in the U.S. for the induction of remission in patients with active, mild to moderate ulcerative colitis.
Tuesday 16 July 2013
Top Selling Schizophrenia Drug Abilify (Aripiprazole)
Aripiprazole (brand names: Abilify, Aripiprex, OPC-14597,) is an atypical antipsychotic drug with the chemical name 7-[4-(2,3-dichlorophenyl)-1-piperazinyl]-butyloxy]-3,4-dihydro-2(1H)-quinolinone. It was first discovered by the Otsuka Pharmaceutical Company, Ltd., based in Japan, and in collaboration with Bristol-Myers Squibb began to market the drug in the United States following the approval by the Food and Drug Administration for schizophrenia in November 2002. According to IMS Health, Abilify was the fourth top-selling drug in the United States in 2011, with sales of $5.2 billion.
Chemical Structure of Aripiprazole (brand names: Abilify)
Chemical Synthesis of Aripiprazole(active ingredient for Abilify)
Experimental Procedures for the preparation of Aripiprazole (Abilify)
US 5,006,528 discloses process for the preparation of Aripiprazole in two steps. The first step comprises synthesis of 7-(4-bromobutoxy)-3,4-dihydrocarbostyril (7-BBQ) by alkylating the hydroxy group of 7-hydroxy-3,4-dihydrocarbostyril (7-HQ) with 1 ,4-dibromobutane using potassium carbonate in water at reflux temperature for 3 hours to obtain 7-BBQ in 68% yield. The resulting 7-BBQ is further reacted with 1- (2,3-dichlorophenyl)-piperazine to obtain Aripiprazole.
Preparation of 7-(4-bromobutoxy)-3,4-dihydro-2(1H)quinolinone (7-(4-bromobutoxy)-3,4-dihydrocarbostyril; 7-BBQ)
7-Hydroxy-3,4-dihydro-2(1H)-quinolinone (aka 7-Hydroxy-3,4-dihydrocarbostyril, 60gm) and potassium carbonate (76.3 gm) were taken in acetonitrile (1200ml) at room temperature. To this tetra butyl ammonium iodide (13.7 gm) and 1 ,4-dibromobutane (238.5gm) were added and heated at 40- 45°C for 24 hours. Reaction mass was cooled upto room temperature and was filtered off. The resulting filtrate was distilled off under vacuum. The resultant mass was cooled to 25-30°C and cyclohexane (300 ml) was added under stirring. The resulting solid was filtered off and was dried. The resulting solid was taken in water and was stirred for few minutes. The solid was filtered and dried under vacuum at 55-60°C for 20 hours to obtain title compound. mp 110.5-111 °C; 1H NMR (DMSO-d6) ä 1.81 (2H, m, -CH2-), 1.95 (2H, m, -CH2-), 2.41 (2H, t, J ) 7 Hz, -CH2CO-), 2.78 (2H, t, J) 7 Hz, -CH2-C-CO-), 3.60 (2H, t, J ) 6 Hz, -CH2Br), 3.93 (2H,t, J ) 6 Hz, O-CH2-), 6.43 (1H, d, J ) 2.5 Hz), 6.49 (1H, dd, J) 2.5, 8 Hz), 7.04 (1H, d, J ) 8 Hz), 9.98 (1H, s, NHCO). Anal. (C13H16NO2Br) C, H, N.
Yield: 73-75%; Purity: 93-95%
Preparation of Aripiprazole (7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one)
7-(4-Bromobutoxy)-l ,2,3,4-tetrahydroquinolin-2-one (50 gm) was taken in acetonitrile (500 ml) at 25-30°C. To this potassium carbonate (67.2 gm) and l-(2,3- dichlorophenyl) piperazine hydrochloride (44.9gm) were added under stirring. The reaction mixture was refluxed at 80-85°C for 8 hours. The reaction mass was cooled to room temperature, filtered and the resulting solid was washed with acetonitrile. To the resulting solid, water was added and was stirred. The solid was filtered off, washed with water and dried under vacuum at 75-80°C for 15 hrs. The resulting crude aripiprazole was crystallized from isopropyl alcohol and water to obtain title compound. Yield: 75-80%; Dimer Impurity: <0.1%. 1H NMR: DMSO-d6 d 9.96 [1H, s, NH]; 7.29 [2H, m, Ar]; 7.13 [1H, q, Ar]; 7.04 [1H, d, Ar]; 6.49 [1H, dd, Ar]; 6.45 [1H, d, Ar]; 3.92 [2H, t, -CH2-O-]; 2.97 [4H, bb,2(-CH2-)]; 2.78 [2H, t, -CH2-N2-)]; 2.39 [4H, m, 2(-CH2-)]; 1.73 [2H, m, - CH2-]; 1.58 [2H, m, -CH2-]. IR:cm-1 3193; 2939; 2804; 1680; 1627; 1579; 1520; 1449; 1375; 1270; 1245; 1192; 1169; 1045; 965; 649; 869; 780; 712; 588.
Preparation of aripiprazole anhydrous Type I using isopropyl alcohol and water
Crude aripiprazole (30 g) was taken in isopropyl alcohol (600 ml) and was heated to 80-85°C. Water (90 ml) was added at the same temperature. Activated carbon was added and the mixture was stirred for 30 minutes at the same temperature. The resulting hot solution was filtered and the bed was washed with hot isopropyl alcohol. The resulting filtrate was cooled to 25-30°C for 4 hours. The resulting solid was filtered, washed with isopropyl alcohol and dried under suction for 1 hour. The resulting wet solid was dried in preheated oven maintained at 100-105°C for 6 hours to obtain title compound.
Yield: 87-89% HPLC Purity: 99.89
Anhydrous crystal D: Below detectable limit (BDL) at limit of detection 1%.
Hydrate A: Below detectable limit (BDL) at limit of detection 1 %.
Particle size distribution: d10=15.83 m, d50=60.12 m, d90=144.99 m
Preparation of aripiprazole anhydrous Type I using ethanol and water
Crude aripiprazole (15 g) was taken in ethanol (300 ml) and water (45 ml) and was heated to 80-85°C for 1-2 hours. The resulting mixture was cooled to 25-30°C within 4 hours and stirred for 3 hours. The resulting solid was filtered and dried under suction for 1 hour. The resulting wet solid was dried in preheated oven maintained at 100-105°C for 3 hours to obtain title compound. Yield: 90% HPLC Purity: 99.9%
Anhydrous crystal D: Below detectable limit (BDL) at limit of detection 1%.
Hydrate A: Below detectable limit (BDL) at limit of detection 1%.
Particle size distribution: d10=22.01 m, d50=105.10 m, d90=232.97 m
References For the Process of Aripiprazole (Abilify,)
Yasuo Oshiro, Seiji Sato, Nobuyuki Kurahashi, Tatsuyoshi Tanaka, Tetsuro Kikuchi, Katsura Tottori, Yasufumi Uwahodo, and Takao Nishi; Novel Antipsychotic Agents with Dopamine Autoreceptor Agonist Properties: Synthesis and Pharmacology of 7-[4-(4-Phenyl-1-piperazinyl)butoxy]- 3,4-dihydro-2(1H)-quinolinone Derivatives; J. Med. Chem. 1998, 41, 658-667
Yasuo Oshiro, Seiji Sato, Nobuyuki Kurahashi; Carbostyril derivatives, Otsuka Pharmaceutical Co., Ltd; US patent 5006528;Issue date: Apr 9, 1991
BANDO, Takuji, YANO, Katsuhiko, FUKANA, Makoto, AOKI, Satoshi ;Method for producing fine particles of aripiprazole anhydride crystals b; OTSUKA PHARMACEUTICAL CO., LTD., WO 2013002420 A1
ZHENG Siji, LIU Xiaoyi, FU Linyong, TAN Bo, ZHOU Min: ARIPIPRAZOLE MEDICAMENT FORMULATION AND PREPARATION METHOD THEREFOR. / FORMULATION DE MÉDICAMENT ARIPIPRAZOLE ET SON PROCÉDÉ DE PRÉPARATION. / SHANGHAI ZHONGXI PHARMACEUTICAL January 2013: WO 2013/000391
CN 201210235157
CN102846543A
CN102850268A;
CN101781246A
GUPTA, Vijay Shankar, KUMAR, Pramod, VIR, Dharam ;Process for producing aripiprazole in anhydrous type i crystals;JUBILANT LIFE SCIENCES LIMITED;WO 2012131451 A1
SRIVASTAVA JAYANT GUPTA Vijay Shankar;Improved process for the preparation of 7.(4-bromobutoxy) 3,4-dihydrocarbostyril, a precursor of aripiprazole;wo2011030213 A1
No Generic Abilify in the US until April 2015
On May 7, 2012, The U.S. Court of Appeals for the Federal Circuit ruled in favor of Otsuka Pharmaceutical Co., Ltd. in its patent litigation against several companies including Israel-based Teva and Weston, Ontario-based Apotex seeking FDA approval to market generic copies of Abilify®. (see the pdf file for the decision upholding the Otsuka patent here). The Federal Circuit affirmed a decision of the U.S. District Court for the District of New Jersey holding that the asserted claims of U.S. Patent No. 5,006,528 (pdf file here) covering aripiprazole, the active ingredient in Abilify®, are valid, thus maintaining patent and regulatory protection for Abilify® in the U.S. until at least April 20, 2015. The case is Otsuka Pharma Co. v. Sandoz Inc., 2011-1126 and 2011-1127, U.S. Court of Appeals for the Federal Circuit (Washington). The lower court case is Otsuka Pharmaceutical Co. v. Sandoz Inc., 07cv1000, U.S. District Court for the District of New Jersey (Trenton).
Chemical Name for Aripiprazole(active ingredient for Abilify): 7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one
CAS number 129722-12-9
CAS number 129722-12-9
Aripiprazole brand names: Abilify, Aripiprex) is a partial dopamine agonist of the second generation class of atypical antipsychotics with additional antidepressant properties that is primarily used in the treatment ofschizophrenia, bipolar disorder, major depressive disorder, and irritability associated with autism.[1] It was approved by the U.S.Food and Drug Administration (FDA) for schizophrenia on November 15, 2002 and the European Medicines Agency on 4 June 2004; for acute manic and mixed episodes associated with bipolar disorder on October 1, 2004; as an adjunct for major depressive disorder on November 20, 2007;[2] and to treat irritability in children with autism on 20 November 2009.[3] Aripiprazole was developed by Otsuka in Japan, and in the United States, Otsuka America markets it jointly with Bristol-Myers Squibb.
Aripiprazole can be synthesized beginning with a dichloroaniline and bis(2-chloroethyl)amine:
Furiex Pharmaceuticals Announces Completion of Patient Enrollment for Its Phase III Clinical Trials of Eluxadoline for IBS-d
http://www.ama-assn.org/resources/doc/usan/eluxadoline.pdf
get the structure of eluxadoline here
name
Benzoic acid, 5-[[[(2S)-2-amino-3-[4-(aminocarbonyl)-2,6-dimethylphenyl]-1-
oxopropyl][(1S)-1-(5-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2-methoxy-
MOLECULAR FORMULA C32H35N5O5
MOLECULAR WEIGHT 569.7
TRADEMARK None as yet
SPONSOR Furiex Pharmaceuticals, Inc.
CODE DESIGNATIONS JNJ-27018966
CAS REGISTRY NUMBER 864821-90-9
WHO NUMBER 9749
read all at
http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=76787#.UeUl4EHDBZg
need phase 2 data see here
In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D. ClinicalTrials.gov number, NCT01130272
get the structure of eluxadoline here
name
Benzoic acid, 5-[[[(2S)-2-amino-3-[4-(aminocarbonyl)-2,6-dimethylphenyl]-1-
oxopropyl][(1S)-1-(5-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2-methoxy-
MOLECULAR FORMULA C32H35N5O5
MOLECULAR WEIGHT 569.7
TRADEMARK None as yet
SPONSOR Furiex Pharmaceuticals, Inc.
CODE DESIGNATIONS JNJ-27018966
CAS REGISTRY NUMBER 864821-90-9
WHO NUMBER 9749
Eluxadoline nonproprietary drug name - AMA
www.ama-assn.org/resources/doc/usan/eluxadoline.pdf
November 28, 2012. N11/133. STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL. USAN (ZZ-82). ELUXADOLINE.Furiex Pharmaceuticals Announces Completion of Patient Enrollment for Its Phase III Clinical Trials of Eluxadoline for IBS-d
Furiex Pharmaceuticals Inc.Posted on:15 Jul 13
Furiex Pharmaceuticals Inc. (NASDAQ: FURX) today announced completion of patient enrollment in the company’s two ongoing Phase III clinical trials studying eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome or IBS-d. Both studies met their target enrollments and Furiex expects to release top line results in the first quarter of 2014.
The two Phase III trials have the same overall design and efficacy endpoints but differ in overall duration. One study has a 52-week treatment period and the other a 30-week treatment period. Each study has three treatment arms placebo 75 mg eluxadoline twice a day and 100 mg eluxadoline twice a day with approximately 375 patients per arm and is designed to capture both the U.S. Food
The two Phase III trials have the same overall design and efficacy endpoints but differ in overall duration. One study has a 52-week treatment period and the other a 30-week treatment period. Each study has three treatment arms placebo 75 mg eluxadoline twice a day and 100 mg eluxadoline twice a day with approximately 375 patients per arm and is designed to capture both the U.S. Food
read all at
http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=76787#.UeUl4EHDBZg
need phase 2 data see here
In a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D. ClinicalTrials.gov number, NCT01130272
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