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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 29 year tenure till date Aug 2016, Around 30 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 13 lakh plus views on New Drug Approvals Blog in 212 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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India’s Strides to buy Aspen’s Australian generic pharmaceutical business


India’s Strides to buy Aspen’s Australian generic pharmaceutical business
India-based Strides Arcolab has signed an agreement with subsidiaries of South African drugmaker Aspen Pharmacare Holdings to acquire its generic pharmaceutical business in Australia and certain branded pharmaceutical assets for around A$380m ($300m).


  About Strides

  • picHeadquartered in India, Strides Arcolab is a pharmaceutical company with a key focus on development and manufacture of IP-led niche generics and bio-pharmaceuticals. It is also among the world’s largest manufacturers of specialty soft gelatin capsules. With world-class manufacturing facilities, an innovative R&D hub in Bangalore and a strong commercial platform to market branded and commodity generics globally, Strides has earned a reputation for building and scaling profitable businesses in a short span of time.



Chandos Street, St Leonards





VX 787, PIMODIVIR, for Avian influenza

(2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridm-3-yl)-5- fluoropyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid
(2S,3S)-3-((5-Fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic Acid
C20 H19 F2 N5 O2

vx 787

Vertex Pharmaceuticals

Janssen Pharmaceuticals, under license from Vertex Pharmaceuticals, is developing VX-787 and its back-up compound VX-353, an influenza A viral replication inhibitor, for treating influenza A virus infection, including pandemic and avian influenza strains. In May 2015, VX-787 was in phase II clinical trial.

Useful for treating influenza virus infection. For concurrent filing see WO2015073476 (claiming the polymorphic forms of VX-787) and WO2015073491 (claiming the composition comprising the hydrochloride salt of VX-787).

Polymorphic forms of hydrochloride (A,F and D) and tosylate salts (form A) of VX-787 are claimed. , useful for treating influenza virus infection. For concurrent filing see WO2015073481 (claiming the processes for the synthesis of VX-787 ) and WO2015073491 (claiming the composition comprising the hydrochloride salt of VX-787).


(1070) (2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridm-3-yl)-5- fluoropyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid

(1070) (2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridm-3-yl)-5- fluoropyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid

Compound 1070 was made in a similar fashion as described above for compounds 946 and 947.


WO 2013019828

WO 2012083122

Synthetic Scheme 1

(a) CHC13; (b) NaOMe, MeOH; (c) DPPA, Et3N, BnOH; (d) H2, Pd/C;

Synthetic Scheme 2

(a) Et3N, CH3CN; (b) cone. H2S04; (c) 9M H2S04; (d) Ag2C03, HOAc, DMSO, 100 °C; (e) X- phos, Pd2(dba)3, K3PO4, 2-methyl THF, H20, 120 °C (f) LiOH, THF, MeOH, 70 °C

Synthetic Scheme 3

(a) Et3N, THF; (b) chiral SFC separation; (c) 5-fluoro- l -(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-


See new patents





Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2

J. Med. Chem., 2014, 57 (15), pp 6668–6678

DOI: 10.1021/jm5007275

Vertex Pharmaceuticals Inc


1H NMR (300 MHz, DMSO-d6) δ 12.71 (br s, 1H), 8.58 (s, 1H), 8.47 (dd, J = 9.6, 2.8 Hz, 1H), 8.41 (d, J = 4.8 Hz, 1H), 8.39–8.34 (m, 1H), 4.89–4.76 (m, 1H), 2.94 (d, J = 6.9 Hz, 1H), 2.05 (br s, 1H), 1.96 (br s, 1H), 1.68 (complex m, 7H);
13C NMR (300 MHz, DMSO-d6) δ 174.96, 157.00, 155.07, 153.34, 152.97, 145.61, 142.67, 140.65, 134.24, 133.00, 118.02, 114.71, 51.62, 46.73, 28.44, 28.00, 24.90, 23.78, 20.88, 18.98;
LCMS gradient 10–90%, 0.1% formic acid, 5 min, C18/ACN, tR = 2.24 min, (M + H) 400.14;
HRMS (ESI) of C20H20F2N5O2 [M + H] calcd, 400.157 95; found, 400.157 56.
June 18, 2014

Vertex Licenses VX-787 to Janssen Pharmaceuticals for the Treatment of Influenza

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that it has entered into a licensing agreement with Janssen Pharmaceuticals, Inc. for the worldwide development and commercialization of VX-787, a novel medicine discovered by Vertex for the treatment of influenza. As part of the agreement, Vertex will receive an up-front payment of $30 million from Janssen and has the potential to receive additional development and commercial milestone payments as well as royalties on future product sales. Vertex completed a Phase 2a study of VX-787 in 2013 that showed statistically significant improvements in viral and clinical measurements of influenza infection. VX-787 is designed to directly inhibit replication of the influenza virus.

“With a deep history in developing new medicines for viral infections and diseases, Janssen is well-positioned to advance the global development of VX-787 for the treatment of influenza,” said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. “This collaboration provides important support for the continued development of VX-787 in influenza and contributes to our financial strength to enable continued investment in our key development programs for cystic fibrosis and in research aimed at discovering new medicines.”

About the Collaboration

Under the terms of the collaboration, Janssen will have full global development and commercialization rights to VX-787. Vertex will receive a $30 million up-front payment from Janssen and could receive additional development and commercial milestone payments as well as royalties on future product sales. The collaboration, and the related $30 million up-front payment, is subject to the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

About VX-787

VX-787 is an investigational medicine that is designed to directly inhibit replication of influenza A, including recent H1 (pandemic) and H5 (avian) influenza strains, based on in-vitro data. VX-787’s mechanism represents a new class of potential medicines for the treatment of influenza, distinct from neuraminidase inhibitors, the current standard of care for the treatment of influenza. VX-787 is intended to provide a rapid onset of action and an expanded treatment window.

In a Phase 2a influenza challenge study, statistically significant improvements in viral and clinical measurements of influenza infection were observed after treatment with VX-787. The study met its primary endpoint and showed a statistically significant decrease in the amount of virus in nasal secretions (viral shedding) over the seven-day study period. In addition, at the highest dosing regimen evaluated in the study, there was a statistically significant reduction in the severity and duration of influenza-like symptoms. In this study, VX-787 was generally well-tolerated, with no adverse events leading to discontinuation. Those who took part in the study volunteered to be experimentally exposed to an attenuated form of live H3N2 influenza A virus. H3N2 is a common type of influenza virus and was the most common type observed in the 2012/2013 influenza season in the United States.

VX-787 was discovered by Vertex scientists.

About Influenza

Often called “the flu,” seasonal influenza is caused by influenza viruses, which infect the respiratory tract.1 The flu can result in seasonal epidemics2 and can produce severe disease and high mortality in certain populations, such as the elderly.3 Each year, on average 5 to 20 percent of the U.S. population gets the flu4 resulting in more than 200,000 flu-related hospitalizations and 36,000 deaths.5 The overall national economic burden of influenza-attributable illness for adults is $83.3 billion.5 Direct medical costs for influenza in adults totaled $8.7 billion including $4.5 billion for adult hospitalizations resulting from influenza-attributable illness.5 The treatment of the flu consists of antiviral medications that have been shown in clinical studies to shorten the disease and reduce the severity of symptoms if taken within two days of infection.6 There is a significant need for new medicines targeting flu that provide a wider treatment window, greater efficacy and faster onset of action.

About Vertex

Vertex is a global biotechnology company that aims to discover, develop and commercialize innovative medicines so people with serious diseases can lead better lives. In addition to our clinical development programs focused on cystic fibrosis, Vertex has more than a dozen ongoing research programs aimed at other serious and life-threatening diseases.

Founded in 1989 in Cambridge, Mass., Vertex today has research and development sites and commercial offices in the United States, Europe, Canada and Australia. For four years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences. For additional information and the latest updates from the company, please visit

Vertex’s press releases are available at

WO2002024705A1 13 Sep 2001 28 Mar 2002 Charles Jackson Barnett Stereoselective process for preparing cyclohexyl amine derivatives
WO2003015798A1 13 Aug 2002 27 Feb 2003 Toyama Chemical Co Ltd Novel virus proliferation inhibition/virucidal method and novel pyradine nucleotide/pyradine nucleoside analogue
WO2005095400A1 30 Mar 2005 13 Oct 2005 Vertex Pharma Azaindoles useful as inhibitors of jak and other protein kinases
WO2006069258A1 * 20 Dec 2005 29 Jun 2006 Amgen Inc Substituted heterocyclic compounds and methods of use
WO2007084557A2 17 Jan 2007 26 Jul 2007 Vertex Pharma Azaindoles useful as inhibitors of janus kinases
WO2008079346A1 21 Dec 2007 3 Jul 2008 Vertex Pharma 5-cyan0-4- (pyrrolo [2, 3b] pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors
WO2009073300A1 31 Oct 2008 11 Jun 2009 Vertex Pharma [1h- pyrazolo [3, 4-b] pyridine-4-yl] -phenyle or -pyridin-2-yle derivatives as protein kinase c-theta
WO2010011756A1 22 Jul 2009 28 Jan 2010 Vertex Pharmaceuticals Incorporated Pyrazolopyridine kinase inhibitors
WO2010011768A1 22 Jul 2009 28 Jan 2010 Vertex Pharmaceuticals Incorporated Tri-cyclic pyrazolopyridine kinase inhibitors
WO2010011772A2 22 Jul 2009 28 Jan 2010 Vertex Pharmaceuticals Incorporated Tri-cyclic pyrazolopyridine kinase inhibitors
WO2010148197A1 * 17 Jun 2010 23 Dec 2010 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
WO2011008915A1 * 15 Jul 2010 20 Jan 2011 Abbott Laboratories Pyrrolopyridine inhibitors of kinases
US20100038988 12 Aug 2008 18 Feb 2010 Gannon Ramy Stator and Method of Making the Same
WO2003015798A1 Aug 13, 2002 Feb 27, 2003 Toyama Chemical Co Ltd Novel virus proliferation inhibition/virucidal method and novel pyradine nucleotide/pyradine nucleoside analogue
WO2005095400A1 Mar 30, 2005 Oct 13, 2005 Vertex Pharma Azaindoles useful as inhibitors of jak and other protein kinases
WO2007084557A2 Jan 17, 2007 Jul 26, 2007 Vertex Pharma Azaindoles useful as inhibitors of janus kinases
WO2009073300A1 Oct 31, 2008 Jun 11, 2009 Vertex Pharma [1h- pyrazolo [3, 4-b] pyridine-4-yl] -phenyle or -pyridin-2-yle derivatives as protein kinase c-theta
WO2010011756A1 Jul 22, 2009 Jan 28, 2010 Vertex Pharmaceuticals Incorporated Pyrazolopyridine kinase inhibitors
WO2010011768A1 Jul 22, 2009 Jan 28, 2010 Vertex Pharmaceuticals Incorporated Tri-cyclic pyrazolopyridine kinase inhibitors
WO2010011772A2 Jul 22, 2009 Jan 28, 2010 Vertex Pharmaceuticals Incorporated Tri-cyclic pyrazolopyridine kinase inhibitors
WO2010148197A1 * Jun 17, 2010 Dec 23, 2010 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
US20100038988 Aug 12, 2008 Feb 18, 2010 Gannon Ramy Stator and Method of Making the Same



Vertex Pharmaceuticals’ Boston Campus, United States of America

Lynette Hopkinson VP Commercial Regulatory Affairs, Global Regulatory Affairs Vertex Pharmaceuticals Incorporated, United States

swati Patel, a lead analyst, shared a toast with Mir Hussain, a systems engineer, at Vertex Pharmaceuticals during the Friday beer hour, which features beer and chips for employees.

On Fridays around 5 o’clock, after a hard week of work, Frank Holland likes to unwind with a beer. And he doesn’t have to leave work to get one.

Holland is a research scientist at Vertex Pharmaceuticals, which every Friday rings in “beer hour,” offering free adult beverages and munchies to its 1,300 Boston employees.

For Holland, the weekly ritual is a chance to escape the bubble of his chemistry lab and bump into colleagues from other departments — as well as Vertex’s top executives, who regularly attend. For those who prefer grapes to hops, there is also wine.

“Some of the other companies I worked at, you really had to go out of your way to meet people,” said Holland, 32. “At Vertex all you have to do is show up in the cafeteria on a Friday afternoon.”

Sure, free beer is common at hip tech offices; some even have their own bars. But Vertex, best known for its treatment for cystic fibrosis, was doing this way before it was cool. The beer-hour tradition goes back to the company’s founding days, in 1989. Back then, it was just two dozen people in a small office in Cambridge. Someone went to a corner store, bought a case of beer and some chips, and beer hour was born.

Virginia Carden Carnahan
Vice President, New Product Planning and Strategy, Vertex Pharmaceuticals

A scientist works in the lab at Boston-based Vertex Pharmaceuticals.

Vertex Pharmaceuticals Headquarters Lobby




Masitinib; 790299-79-5; Masivet; AB1010; AB-1010;

TARGET:KIT (a stem cell factor, also called c-KIT) receptor as well as select other tyrosine kinases
COMMERCIAL:Under development by AB Science..Ab Science
AB 1010


Regulatory and Commercial Status

Marketing Authorization Application for the treatment of pancreatic cancer has been filed with the European Medicines Agency (16 October 2012)
Marketing Authorization Application for the conditional approval in the treatment of pancreatic cancer has been accepted by the European Medicines Agency (30 October 2012)


Masitinib is a tyrosine-kinase inhibitor used in the treatment of mast cell tumors in animals, specifically dogs.[1][2] Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. In the USA it is distributed under the name Kinavet and has been available for veterinaries since 2011.

Masitinib is being studied for several human conditions including cancers. It is used in Europe to fight orphan diseases.[3]

Mechanism of action

Masitinib inhibits the receptor tyrosine kinase c-Kit which is displayed by various types of tumour.[2] It also inhibits the platelet derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR).


Compound Synthesis

General: All chemicals used were commercial reagent grade products. Dimethylformamide (DMF), methanol (MeOH) were of anhydrous commercial grade and were used without further purification. Dichloromethane and tetrahydrofuran (THF) were freshly distilled under a stream of argon before use. The progress of the reactions was monitored by thin layer chromatography using precoated silica gel 60F 254, Fluka TLC plates, which were visualized under UV light. Multiplicities in 1H NMR spectra are indicated as singlet (s), broad singlet (br s), doublet (d), triplet (t), quadruplet (q), and multiplet (m) and the NMR spectrum were realized on a 300 MHz Bruker spectrometer.

3-Bromoacetyl-pyridine, HBr Salt

Dibromine (17.2 g, 108 mmol) was added dropwise to a cold (0° C.) solution of 3-acetyl-pyridine (12 g, 99 mmol) in acetic acid containing 33% of HBr (165 mL) under vigourous stirring. The vigorously stirred mixture was warmed to 40° C. for 2 h and then to 75° C. After 2 h at 75° C., the mixture was cooled and diluted with ether (400 mL) to precipitate the product, which was recovered by filtration and washed with ether and acetone to give white crystals (100%). This material may be recrystallised from methanol and ether.

IR (neat): 3108, 2047, 2982, 2559, 1709, 1603, 1221, 1035, 798 cm−1−1H NMR (DMSO-d6) δ=5.09 (s, 2H, CH2Br); 7.88 (m, 1H, pyridyl-H); 8.63 (m, 1H, pyridyl-H); 8.96 (m, 1H, pyridyl-H); 9.29 (m, 1H, pyridyl-H).


To methyl-4-formyl benzoate (4.92 g, 30 mmol) and N-methyl-piperazine (3.6 mL, 32 mmol) in acetonitrile (100 mL) was added dropwise 2.5 mL of trifluoroacetic acid. The reaction mixture was stirred at room temperature for 1 h. After slow addition of sodium cyanoborohydride (2 g, 32 mmol), the solution was left stirring overnight at room temperature. Water (10 mL) was then added to the mixture, which was further acidified with 1N HCl to pH=6-7. The acetonitrile was removed under reduced pressure and the residual aqueous solution was extracted with diethyl ether (4×30 mL). These extracts were discarded. The aqueous phase was then basified (pH>12) by addition of 2.5N aqueous sodium hydroxyde solution. The crude product was extracted with ethyl acetate (4×30 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to afford a slightly yellow oil which became colorless after purification by Kugelrohr distillation (190° C.) in 68% yield.

IR(neat): 3322, 2944, 2802, 1721, 1612, 1457, 1281, 1122, 1012—1H NMR(CDCl3) δ=2.27 (s, 3H, NCH3); 2.44 (m, 8H, 2×NCH2CH2N); 3.53 (s, 2H, ArCH2N); 3.88 (s, 3H, OCH3); 7.40 (d, 2H, J=8.3 Hz, 2×ArH); 7.91 (d, 2H, J=8.3 Hz, 2×ArH)—3C NMR (CDCl3) δ=45.8 (NCH3); 51.8 (OCH3); 52.9 (2×CH2N); 54.9 (2×CH2N); 62.4 (ArCH2N); 128.7 (2×ArC); 129.3 (2×ArC); 143.7 (ArC); 166.7 (ArCO2CH3)-MS CI (m/z) (%) 249 (M+1, 100%).


A solution of di-tert-butyldicarbonate (70 g, 320 mmol) in methanol (200 mL) was added over 2 h to a cold (−10° C.) solution of 2,4-diaminotoluene (30 g, 245 mmol) and triethylamine (30 mL) in methanol (15 mL). The reaction was followed by thin layer chromatography (hexane/ethyl acetate, 3:1) and stopped after 4 h by adding 50 mL of water. The mixture was concentrated in vacuo and the residue was dissolved in 500 mL of ethyl acetate. This organic phase was washed with water (1×150 mL) and brine (2×150 mL), dried over MgSO4, and concentrated under reduced pressure. The resulting light brown solid was washed with small amounts of diethyl ether to give off-white crystals of 2-methyl-5-tert-butoxycarbonylamino-aniline in 67% yield.

IR (neat): 3359; 3246; 2970; 1719; 1609; 1557; 1173; 1050 cm−11H NMR (CDCl3): δ=1.50 (s, 9H, tBu); 2.10 (s, 3H, ArCH3); 3.61 (br s, 2H, NH2); 6.36 (br s, 1H, NH); 6.51 (dd, 1H, J=7.9 Hz, 2.3 Hz, ArH); 6.92 (d, 1H, J=7.9 Hz, ArH); 6.95 (s, 1H, ArH)—13C NMR (CDCl3) δ=16.6 (ArCH3); 28.3 (C(CH3)3); 80.0 (C(CH3)3); 105.2 (ArC); 108.6 (ArC); 116.9 (ArC); 130.4 (ArC—CH3); 137.2 (ArC—NH); 145.0 (ArC—NH2); 152.8 (COOtBu) MS ESI (m/z) (%): 223 (M+1), 167 (55, 100%).


Benzoyl chloride (5.64 g, 80 mmol) was added dropwise to a well-stirred solution of ammonium thiocyanate (3.54 g, 88 mmol) in acetone (50 mL). The mixture was refluxed for 15 min, then, the hydrobromide salt of 2-methyl-5-tert-butoxycarbonylamino-aniline (8.4 g, 80 mmol) was added slowly portionswise. After 1 h, the reaction mixture was poured into ice-water (350 mL) and the bright yellow precipitate was isolated by filtration. This crude solid was then refluxed for 45 min in 70 mL of 2.5 N sodium hydroxide solution. The mixture was cooled down and basified with ammonium hydroxide. The precipitate of crude thiourea was recovered by filtration and dissolved in 150 mL of ethyl acetate. The organic phase was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (hexane/ethyl acetate, 1:1) to afford 63% of N-(2-methyl-5-tert-butoxycarbonylamino)phenyl-thiourea as a white solid.

IR (neat): 3437, 3292, 3175, 2983, 1724, 1616, 1522, 1161, 1053 cm−1— 1H NMR (DMSO-d6) δ=1.46 (s, 9H, tBu); 2.10 (s, 3H, ArCH3); 3.60 (br s, 2H, NH2); 7.10 (d, 1H, J=8.29 Hz, ArH); 7.25 (d, 1H, J=2.23 Hz, ArH); 7.28 (d, 1H, J=2.63 Hz, ArH); 9.20 (s, 1H, ArNH); 9.31 (s, 1H, ArNH)—13C NMR (DMSO-d6) δ=25.1 (ArCH3); 28.1 (C(CH3)3); 78.9 (C(CH3)3); 16.6 (ArC); 117.5 (ArC); 128.0 (ArC); 130.4 (ArC—CH3); 136.5 (ArC—NH); 137.9 (ArC—NH); 152.7 (COOtBu); 181.4 (C═S)—MS CI(m/z): 282 (M+1, 100%); 248 (33); 226 (55); 182 (99); 148 (133); 93 (188).


A mixture of 3-bromoacetyl-pyridine, HBr salt (0.81 g, 2.85 mmol), N-(2-methyl-5-tert-butoxycarbonylamino)phenyl-thiourea (0.8 g, 2.85 mmol) and KHCO3 (˜0.4 g) in ethanol (40 mL) was heated at 75° C. for 20 h. The mixture was cooled, filtered (removal of KHCO3) and evaporated under reduced pressure. The residue was dissolved in CHCl3 (40 mL) and washed with saturated aqueous sodium hydrogen carbonate solution and with water. The organic layer was dried over Na2SO4 and concentrated. Colum chromatographic purification of the residue (hexane/ethyl acetate, 1:1) gave the desired thiazole in 70% yield as an orange solid

IR(neat): 3380, 2985, 2942, 1748, 1447, 1374, 1239, 1047, 938—1H NMR (CDCl3) δ=1.53 (s, 9H, tBu); 2.28 (s, 3H, ArCH3); 6.65 (s, 1H, thiazole-H); 6.89 (s, 1H); 6.99 (dd, 1H, J=8.3 Hz, 2.3 Hz); 7.12 (d, 2H, J=8.3 Hz); 7.35 (dd, 1H, J=2.6 Hz, 4.9 Hz); 8.03 (s, 1H); 8.19 (dt, 1H, J=1.9 Hz, 7.9 Hz); 8.54 (br s, 1H, NH); 9.09 (s, 1H, NH)—13C NMR (CDCl3) δ=18.02 (ArCH3); 29.2 (C(CH3)3); 81.3 (C(CH3)3); 104.2 (thiazole-C); 111.6; 115.2; 123.9; 124.3; 131.4; 132.1; 134.4; 139.5; 148.2; 149.1; 149.3; 153.6; 167.3 (C═O)—MS Cl (m/z) (%): 383 (M+1, 100%); 339 (43); 327 (55); 309 (73); 283 (99); 71 (311).


2-(2-methyl-5-tert-butoxycarbonylamino)phenyl-4-(3-pyridyl)-thiazole (0.40 g, 1.2 mmol) was dissolved in 10 mL of 20% TFA/CH2Cl2. The solution was stirred at rool temperature for 2 h, then it was evaporated under reduced pressure. The residue was dissolved in ethyl acetate. The organic layer was washed with aqueous 1N sodium hydroxide solution, dried over MgSO4, and concentrated to afford 2-(2-methyl-5-amino)phenyl-4-(3-pyridyl)-thiazole as a yellow-orange solid in 95% yield. This crude product was used directly in the next step.

A 2M solution of trimethyl aluminium in toluene (2.75 mL) was added dropwise to a cold (0° C.) solution of 2-(2-methyl-5-amino)phenyl-4-(3-pyridyl)-thiazole (0.42 g, 1.5 mmol) in anhydrous dichloromethane (10 mL) under argon atmosphere. The mixture was warmed to room temperature and stirred at room temperature for 30 min. A solution of methyl-4-(1-N-methyl-piperazino)-methyl benzoate (0.45 g, 1.8 mmol) in anhydrous dichloromethane (1 mL) and added slowly, and the resulting mixture was heated at reflux for 5 h. The mixture was cooled to 0° C. and quenched by dropwise addition of a 4N aqueous sodium hydroxide solution (3 mL). The mixture was extracted with dichloromethane (3×20 mL). The combined organic layers were washed with brine (3×20 mL) and dried over anhydrous MgSO4. (2-(2-methyl-5-amino)phenyl-4-(3-pyridyl)-thiazole) is obtained in 72% after purification by column chromatography (dichloromethane/methanol, 3:1)

IR (neat): 3318, 2926, 1647, 1610, 1535, 1492, 1282, 1207, 1160, 1011, 843—

1H NMR (CDCl3) δ=2.31 (br s, 6H, ArCH3+NCH3); 2.50 (br s, 8H, 2×NCH2CH2N); 3.56 (s, 2H, ArCH2N); 6.89 (s, 1H, thiazoleH); 7.21-7.38 (m, 4H); 7.45 (m, 2H); 7.85 (d, 2H, J=8.3 Hz); 8.03 (s, 1H); 8.13 (s, 1H); 8.27 (s, 1H); 8.52 (br s, 1H); 9.09 (s, 1H, NH)—

13C NMR (CDCl3) δ 17.8 (ArCH3); 46.2 (NCH3); 53.3 (NCH2); 55.3 (NCH2); 62.8 (ArCH2N); 99.9 (thiazole-C); 112.5; 123.9; 125.2; 127.5; 129.6; 131.6; 133.7; 134.0; 137.6; 139.3; 142.9; 148.8; 149.1; 166.2 (C═O); 166.7 (thiazoleC-NH)—

MS CI (m/z) (%): 499 (M+H, 100%); 455 (43); 430 (68); 401 (97); 374 (124); 309 (189); 283 (215); 235 (263); 121 (377); 99 (399).


In a preferred embodiment of the above-depicted treatment, the active ingredient masitinib is administered in the form of masitinib mesilate; which is the orally bioavailable mesylate salt of masitinib – CAS 1048007-93-7 (MsOH); C28H30N6OS.CH3SO3H; MW 594.76:

Figure imgf000031_0001

Figure imgf000021_0001

003 : 4-(4-Methyl-piperazin-l-ylmethyl)-N-[3-(4-pyridin-3-yl-thiazol-2-ylamino)- phenyl] -benzamide

4-(4-Methyl-piperazin-l-yl)-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylmethyl)- phenyl] -benzamide

Figure imgf000053_0001

beige brown powder mp : 128-130°C

1H RMN (DMSO-d6) δ = 2.15 (s, 3H) ; 2.18 (s, 3H) ; 2.35-2.41 (m, 4H) ; 3.18-3.3.24 (m, 4H) ; 6.94 (d, J = 8.9 Hz, 2H) ; 7.09 (d, J = 8.4 Hz, IH) ; 7.28-7.38 (m, 3H) ; 7.81 (d, J = 8.9 Hz, 2H) ; 8.20-8.25 (m, IH) ; 8.40 (dd, J = 1.6 Hz, J = 4.7 , IH) ; 8.48 (d, J = 1.9 Hz, IH) ; 9.07 (d, J = 1.5 Hz, IH) ; 9.35 (s, IH) ; 9.84 (s, IH)


EXAMPLE 4 N- [4-Methyl-3 -(4-pyridin-3 -yl-thiazol-2-ylamino)-phenyl] -benzamide derivatives

Method A In a reactor and under low nitrogen pressure, add 4-Methyl-N3-(4-pyridin-3-yl-thiazol- 2-yl)-benzene-l,3-diamine (95 g, 336.45 mmol), dichloromethane (2 L). To this suspension cooled to temperature of 5°C was added dropwise 2M/n-hexane solution of trimethylaluminium (588 mL). The reaction mixture was brought progressively to 15°C, and maintained for 2 h under stirring. 4-(4-Methyl-piperazin-l-ylmethyl)-benzoic acid methyl ester (100 g, 402.71 mmol) in dichloromethane (200 mL) was added for 10 minutes. After 1 h stirring at room temperature, the reaction mixture was heated to reflux for 20 h and cooled to room temperature. This solution was transferred dropwise via a cannula to a reactor containing 2N NaOH (2.1 L) cooled to 5°C. After stirring for 3 h at room temperature, the precipitate was filtered through Celite. The solution was extracted with dichloromethane and the organic layer was washed with water and saturated sodium chloride solution, dried over MgSO4 and concentrated under vacuum. The brown solid obtained was recrystallized from /-Pr2O to give 130.7 g (78%) of a beige powder.

Method B Preparation of the acid chloride

To a mixture of 4-(4-Methyl-piperazin-l-ylmethyl)-benzoic acid dihydrochloride (1.0 eq), dichloromethane (7 vol) and triethylamine (2.15 eq), thionyl chloride (1.2 eq) was added at 18-28°C . The reaction mixture was stirred at 28-32°C for 1 hour. Coupling of acid chloride with amino thiazole To a chilled (0-50C) suspension of 4-Methyl-N3-(4-pyridin-3-yl-thiazol-2-yl)-benzene- 1,3-diamine (0.8 eq) and thiethylamine (2.2 eq) in dichloromethane (3 vol), the acid chloride solution (prepared above) was maintaining the temperature below 5°C. The reaction mixture was warmed to 25-300C and stirred at the same temperature for 1O h. Methanol (2 vol) and water (5 vol) were added to the reaction mixture and stirred. After separating the layers, methanol (2 vol), dihloromethane (5 vol) and sodium hydroxide solution (aqueous, 10%, till pH was 9.5-10.0) were added to the aqueous layer and stirred for 10 minutes. The layers were separated. The organic layer was a washed with water and saturated sodium chloride solution. The organic layer was concentrated and ethanol (2 vol) was added and stirred. The mixture was concentrated. Ethanol was added to the residue and stirred. The product was filtered and dried at 50-550C in a vaccum tray drier. Yield = 65-75%.

Method C

To a solution of 4-methyl-N3-(4-pyridin-3-yl-thiazol-2-yl)-benzene-l,3-diamine (1.0 eq) in DMF (20 vol) were added successively triethylamine (5 eq), 2-chloro-l- methylpyridinium iodide (2 eq) and 4-(4-methyl-piperazin-l-ylmethyl)-benzoic acid (2 eq). The reaction mixture was stirred for 7 h at room temperature. Then, the mixture was diluted in diethyl ether and washed with water and saturated aqueous NaHCO3, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography using an elution of 100% EtOAc to give a yellow solid.

Yield = 51%.

1H NMR (CDCl3) : δ = 9.09 (IH, s, NH); 8.52 (IH, br s); 8.27 (IH, s); 8.13 (IH, s);

8.03 (IH, s); 7.85 (2H, d, J= 8.3Hz); 7.45 (2H, m); 7.21-7.38 (4H, m); 6.89 (IH, s);

3.56 (2H, s); 2.50 (8H, br s); 2.31 (6H, br s).

MS (CI) m/z = 499 (M+H)+.

An additional aspect of the present invention relates to a particular polymorph of the methanesulfonic acid salt of N-[4-Methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]- benzamide of formula (IX).

Figure imgf000023_0001


Hereinafter is described the polymorph form of (IX) which has the most advantageous properties concerning processability, storage and formulation. For example, this form remains, dry at 80% relative humidity and thermodynamically stable at temperatures below 2000C.

The polymorph of this form is characterized by an X-ray diffraction pattern illustrated in FIG.I, comprising characteristic peaks approximately 7.269, 9.120, 11.038, 13.704, 14.481, 15.483, 15.870, 16.718, 17.087, 17.473, 18.224, 19.248, 19.441, 19.940, 20.441, 21.469, 21.750, 22.111, 23.319, 23.763, 24.120, 24.681, 25.754, 26.777, 28.975, 29.609, 30.073 degrees θ, and is also characterized by differential scanning calorimetry (DSC) illustrated in FIG.II, which exhibit a single maximum value at approximately 237.49 ± 0.3 0C. X-ray diffraction pattern is measured using a Bruker AXS (D8 advance). Differential scanning calorimetry (DSC) is measured using a Perking Elmer Precisely (Diamond DSC).

This polymorph form can be obtained by treatement of 4-(4-Methyl-piperazin-l- ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-thiazol-2-ylamino)-phenyl]-benzamide with 1.0 to 1.2 equivalent of methanesulfonic acid, at a suitable temperature, preferably between 20-800C.

The reaction is performed in a suitable solvent especially polar solvent such as methanol or ethanol, or ketone such as acetone, or ether such as diethylether or dioxane, or a mixture therof. This invention is explained in example given below which is provided by way of illustration only and therefore should not be construed to limit the scope of the invention. Preparation of the above-mentioned polymorph form of 4-(4-Methyl-piperazin-l- ylmethyl)-N- [4-methyl-3 -(4-pyridin-3 -yl-thiazol-2-ylamino)-phenyl] -benzamide methanesulfonate .

4-(4-Methyl-piperazin- 1 -ylmethyl)-N- [4-methyl-3 -(4-pyridin-3 -yl-thiazol-2-ylamino) phenyl] -benzamide (1.0 eq) was dissolved in ethanol (4.5 vol) at 65-700C. Methanesulfonic acid (1.0 eq) was added slowly at the same temperature. The mixture was cooled to 25-300C and maintained for 6 h. The product was filtered and dried in a vacuum tray drier at 55-600C. Yield = 85-90%. Starting melting point Smp = 236°C.



CAS NO. 1048007-93-7, methanesulfonic acid,4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide H-NMR spectral analysis

methanesulfonic acid,4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide NMR spectra analysis, Chemical CAS NO. 1048007-93-7 NMR spectral analysis, methanesulfonic acid,4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide H-NMR spectrum

methanesulfonic acid,4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide NMR spectra analysis, Chemical CAS NO. 1048007-93-7 NMR spectral analysis, methanesulfonic acid,4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide C-NMR spectrum

CAS NO. 1048007-93-7, methanesulfonic acid,

4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide C-NMR spectral analysisPREDICT


  1. Hahn, K.A.; Oglivie, G.; Rusk, T.; Devauchelle, P.; Leblanc, A.; Legendre, A.; Powers, B.; Leventhal, P.S.; Kinet, J.-P.; Palmerini, F.; Dubreuil, P.; Moussy, A.; Hermine, O. (2008). “Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors”. Journal of Veterinary Internal Medicine 22 (6): 1301–1309. doi:10.1111/j.1939-1676.2008.0190.x. ISSN 0891-6640.
  2. Information about Masivet at the European pharmacy agency website
  3. Orphan designation for Masitinib at the European pharmacy agency website
WO2004014903A1 Jul 31, 2003 Feb 19, 2004 Ab Science 2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors
WO2008098949A2 Feb 13, 2008 Aug 21, 2008 Ab Science Process for the synthesis of 2-aminothiazole compounds as kinase inhibitors
EP1525200B1 Jul 31, 2003 Oct 10, 2007 AB Science 2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors
US7423055 Aug 1, 2003 Sep 9, 2008 Ab Science 2-(3-Aminoaryl)amino-4-aryl-thiazoles for the treatment of diseases
US20080207572 * Jul 13, 2006 Aug 28, 2008 Ab Science Use of Dual C-Kit/Fgfr3 Inhibitors for Treating Multiple Myeloma
Systematic (IUPAC) name
Clinical data
Trade names Masivet, Kinavet
AHFS/ International Drug Names
PubChem CID 10074640
ChemSpider 8250179
Chemical data
Formula C28H30N6OS
498.64 g/mol
Patent Submitted Granted
2-(3-Aminoaryl)amino-4-aryl-thiazoles for the treatment of diseases [US7423055] 2004-06-10 2008-09-09
2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors [US2005239852] 2005-10-27
Use of C-Kit Inhibitors for Treating Fibrosis [US2007225293] 2007-09-27
Use of Mast Cells Inhibitors for Treating Patients Exposed to Chemical or Biological Weapons [US2007249628] 2007-10-25
Use of c-kit inhibitors for treating type II diabetes [US2007032521] 2007-02-08
Use of tyrosine kinase inhibitors for treating cerebral ischemia [US2007191267] 2007-08-16
Use of C-Kit Inhibitors for Treating Plasmodium Related Diseases [US2008004279] 2008-01-03
Tailored Treatment Suitable for Different Forms of Mastocytosis [US2008025916] 2008-01-31
Use Of C-Kit Inhibitors For Treating Inflammatory Muscle Disorders Including Myositis And Muscular Dystrophy [US2008146585] 2008-06-19
Patent Submitted Granted
Aminothiazole compounds as kinase inhibitors and methods of using the same [US8940894] 2013-05-10 2015-01-27
Aminothiazole compounds as kinase inhibitors and methods of using the same [US8492545] 2012-03-08 2013-07-23
Patent Submitted Granted
Use of Dual C-Kit/Fgfr3 Inhibitors for Treating Multiple Myeloma [US2008207572] 2008-08-28
Anti-IGF antibodies [US8580254] 2008-06-19 2013-11-12
Anti-IGF antibodies [US8318159] 2009-12-11 2012-11-27
ANTI CD37 ANTIBODIES [US2010189722] 2008-08-08 2010-07-29
United States National Library of Medicine

Note: Compound name must be entered under “Substance Identification” and then “Names and Synonyms” selected to view synonyms.

Kocic I, Kowianski P, Rusiecka I, Lietzau G, Mansfield C, Moussy A, Hermine O, Dubreuil P
Naunyn Schmiedebergs Arch Pharmacol. 2014 Oct 26. Epub 2014 Oct 26. PMID: 25344204.Abstract
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P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.


Tajikistan – Wikipedia, the free encyclopedia

The territory that now constitutes Tajikistan was previously home to several ancient cultures, including the city of Sarazm of the Neolithic and the Bronze Age, …

Map of tajikistan country.
The nature of Tajikistan. Nurek
Tajikistan. Pamiro-Alay.Zeravshan mountain range. Guzn village. Local people
Dushanbe, Tajikistan
Women carry water canisters near Gargara village, 110km south of Tajikistan’s capital, Dushanbe
Ancient Buddhist ruins, Ajina Teppa, Tajikistan

β-Sitosterol, 후박(厚朴)


  C29H50O, 414.00
  White needles
m.p(℃)   283-285
IR(cm-¹) νmax (KBr): 3400, 1680
UV(nm) λmax (MeOH): 216
MS EIMS m/z: 414 [M]+



β-Sitosterol (β-谷甾醇); CAS: 83-46-5

(300 MHz, CDCl3) δ: 5.36 (1H, d, J = 5.2 Hz, H-6), 3.53 (1H, m, H-3),1.01 (3H, s, CH3-19), 0.94 (3H, d, J = 6.5 Hz, CH3-21), 0.92 (3H, d, J = 6.5 Hz,CH3-26), 0.83 (3H, t, J = 6.6 Hz, CH3-29), 0.69 (3H, s, CH3-18)


13c nmr

(75 MHz, CDCl3) δ: 37.2 (C-1), 32.1 (C-2), 72.0 (C-3), 42.5 (C-4), 141.0 (C-5), 121.9 (C-6), 32.1 (C-7), 31.9 (C-8), 50.4 (C-9), 36.7 (C-10), 21.3 (C-11), 40.0 (C-12), 42.5 (C-13), 57.0 (C-14), 24.5 (C-15), 28.4 (C-16), 56.3 (C-17), 12.2 (C-18), 19.2 (C-19), 36.3 (C-20), 19.0 (C-21), 34.2 (C-22), 26.4 (C-23),46.1 (C-24), 29.4 (C-25), 19.6 (C-26), 20.0 (C-27), 23.3 (C-28),12.0 (C-29)



ZSTK 474



ZSTK474; 475110-96-4; 4,4′-(6-(2-(Difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine; ZSTK-474; ZSTK 474; TCMDC-137004;



Zenyaku Kogyo (Innovator)

phase2………Treatment of Solid Tumors Therapy

ZSTK474 is a cell permeable and reversible P13K inhibitor with an IC₅₀ at 6nm. It was identified as part of a screening library, selected for its ability to block tumor cell growth. ZSTK474 has shown strong antitumor activities against human cancer xenographs when administered orally to mice without a significant toxic effect.

Phosphatidylinositol 3-kinase (PI3K) has been implicated in a variety of diseases including cancer. A number of PI3K inhibitors have recently been developed for use in cancer therapy. ZSTK474 is a highly promising antitumor agent targeting PI3K. We previously reported that ZSTK474 showed potent inhibition against four class I PI3K isoforms but not against 140 protein kinases.

However, whether ZSTK474 inhibits DNA-dependent protein kinase (DNA-PK), which is structurally similar to PI3K, remains unknown. To investigate the inhibition of DNA-PK, we developed a new DNA-PK assay method using Kinase-Glo. The inhibition activity of ZSTK474 against DNA-PK was determined, and shown to be far weaker compared with that observed against PI3K. The inhibition selectivity of ZSTK474 for PI3K over DNA-PK was significantly higher than other PI3K inhibitors, namely NVP-BEZ235, PI-103 and LY294002.

Other Names: ZSTK-474

Chemical Formula:  C19H21F2N7O2

CAS Number: 475110-96-4

Molecular Weight: 417.41



WO 2002088112

The condensation of 2,4-dichloro-6-(4-morpholinyl)-1,3,5-triazine

with 2-(difluoromethyl)-1H-benzimidazole  by means of K2CO3 in DMF gives

2-chloro-4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazine ,


which is then condensed with morpholine by means of K2CO3 in DMF to afford the target trisubstituted triazine.



aReagents and conditions: (i) K2CO3, DMF, room temp; (ii) morpholine, DMF or THF, room temp; (iii) NaH or K2CO3, DMF or DMSO, 120 °C.


  • 2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine(compound 19)
    Melting point: 211-214°C
    NMR(CDCl3) δ : 3.79(8H, t, J=4Hz), 3.88(8H, t, J=4Hz), 7.3-7.4(2H, m), 7.56(1H, t, J=53Hz), 7.88(1H, d, J=7Hz), 8.32(1H, d, J=7Hz)
    MS m/z: 417(M+



J. Med. Chem., 2011, 54 (20), pp 7105–7126
DOI: 10.1021/jm200688y
1 (0.35 g, 84% yield): mp (EtOH) 217–219 °C (lit. 211–214 °C);

1H NMR (CDCl3) δ 8.33 (dd, J = 7.3, 1.4 Hz, 1H), 7.89 (dd, J = 7.2, 1.5 Hz, 1H), 7.56 (t, JHF= 53.6 Hz, 1H), 7.46–7.37 (m, 2H), 3.91–3.86 (m, 8H), 3.81–3.76 (m, 8H).

Kawashima, S.; Matsuno, T.; Yaguchi, S.; Sasahara, H.; Watanabe, T.Preparation of Heterocyclic Compounds as Antitumor Agents. PCT Int. Appl. WO 02088112, 2002;
Chem. Abstr. 2002, 137, 370113.
A mixture of o-phenylenediamine (5.41 g, 50 mmol) and difluoroacetic acid (9.6 g, 100 mmol) in 4 M HCl (20 mL) was heated under reflux for 1 h and diluted with hot water (50 mL). The solution was treated with charcoal and filtered through Celite before being neutralized with aqueous NH3. The resulting white precipitate was collected, washed with water, and dried to give 2-(difluoromethyl)-1H-benzimidazole  (6.07 g, 72% yield): mp 156–158 °C; 1H NMR (DMSO-d6) δ 13.28 (br, 1H), 7.76–7.68 (m, 1H), 7.61–7.54 (m, 1H), 7.36–7.26 (m, 2H), 7.26 (t,JHF= 53.3 Hz, 1H).
Ge, F.; Wang, Z.; Wan, W.; Lu, W.; Hao, J.One-pot synthesis of 2-trifluoromethyl and 2-difluoromethyl substituted benzo-1,3-diazoles Tetrahedron Lett. 2007, 48, 32513254


Patent Submitted Granted
Heterocyclic compound and antitumor agent containing the same as active ingredient [US7071189] 2004-06-17 2006-07-04
Treatment of prostate cancer, melanoma or hepatic cancer [US2007244110] 2007-10-18
Heterocyclic compound and antitumor agent containing the same as effective ingredient [US7307077] 2006-11-02 2007-12-11


Zenyaku Kogyo

Sector: Health Care
Industry: Biotech & Pharma
Sub-Industry: Specialty Pharma
Zenyaku Kogyo Co. Ltd. produces pharmaceuticals. The Company manufactures and sells over-the-counter drugs, health foods, and prescription medicines, as well as skin care products.
5-6-15 Otsuka
Bunkyo, 112-8650
Map of Otsuka, Bunkyo, Tokyo 112-0012, Japan

S-flurbiprofen (TT-063)


Cas 51543-39-6,

MW 244.26,

MF C15 H13 F O2
[1,​1′-​Biphenyl]​-​4-​acetic acid, 2-​fluoro-​α-​methyl-​, (αS)​-
  • [1,1′-Biphenyl]-4-acetic acid, 2-fluoro-α-methyl-, (S)-
  • (+)-(S)-Flurbiprofen
  • (+)-Flurbiprofen
  • (2S)-2-(2-Fluoro-1,1′-biphenyl-4-yl)propanoic acid
  • (2S)-2-(2-Fluoro-4-biphenyl)propanoic acid
  • (S)-Flurbiprofen
  • Dexflurbiprofen
  • Esflurbiprofen
  • S-(+)-Flurbiprofen
  • d-Flurbiprofen

On October 20, 2014, Taisho filed for manufacturing and marketing approval for TT-063 from the Ministry of Health, Labour and Welfare as a new drug candidate that will follow the Type 2 diabetes treatment Lusefi®, which was launched in May 2014. TT-063 is a patch formulation that has been co-developed by Taisho and TOKUHON Corporation with the aim of obtaining an indication for osteoarthritis. In Phase 3 clinical trials comparing TT-063 with therapeutic drugs already on the market, TT-063 has been found to be more effective than the control drugs in patients with osteoarthritis of the knee joint (January 16, 2014 announcement ).

Furthermore, Taisho is also preparing to file for approval from the Ministry of Health, Labour and Welfare for CT-064, an oral formulation of the osteoporosis treatment agent Bonviva launched in August 2013. Taisho has confirmed the effectiveness of CT-064 for osteoporosis patients through Phase 3 clinical trials (September 22, 2014 announcement).

In the central nervous system field, TS-091 transitioned from Phase 1 to Phase 2 in Japan in May 2014. Clinical trials of TS-091 have commenced to confirm the effectiveness of this drug in patients with central disorders of hypersomnolence. In addition, Phase 1 clinical trials of TS-091 have commenced overseas. TS-111 and TS-121 are undergoing Phase 1 clinical trials overseas with the aim of obtaining an indication for depression.
Faced with intensifying competition in new drug discovery, we will jointly implement R&D activities with research institutions outside the Taisho Group, and with companies in Japan and overseas, as we work to enhance our drug development pipeline (lineup of drugs in development). Our goal is to discover many more new drugs, primarily in our priority fields.

Company Taisho Pharmaceutical Holdings Co. Ltd.
Description Topical anti-inflammatory analgesic patch containing S-flurbiprofen
Therapeutic Modality Small molecule
Latest Stage of Development Phase III
Standard Indication Osteoarthritis
Indication Details Treat osteoarthritis (OA) and scapulohumeral periarthritis
Regulatory Designation

Full-size image (93 K)

Scheme 2.

Reagents and conditions: (a) THF, EDC, Et3N; (b) TFA; (c) 0.5 equiv 2,5-dimethoxybenzoquinone, EtOH, 50–80 °C for 3–5 h; (d) 1 equiv naphthoquinone, MeOH, rt, overnight.


2-(6-methoxynaphthalen-2-yl) propanoic acid By way of illustration, chemically, flurbiprofen is 2-(2-fluoro-4-biphenylyl) propionic acid and is described in US Patent No. 3,755,427. NSAIDs, such as flurbiprofen, are usually supplied as a racemate. However, recently there has been renewed interest in the separate enantiomers of flurbiprofen, i.e. S-flurbiprofen and R-flurbiprofen.

Figure imgf000004_0001


Figure imgf000004_0002


Flurbiprofen is a potent inhibitor of cyclooxygenase (both COX-I and COX-2) in humans and it is understood that the inhibitory effect lies predominantly in the S- enantiomer.

Flurbiprofen is generally produced in the form of a racemic compound. It is known that from the racemic compound, flurbiprofen having a high optical purity can be produced by an optical resolution method using, for example, an optically active amine compound, such as α-phenylethylamine, as an optical resolution agent, as is described in US Patent No. 5,599,969. In addition, whether dealing with racemic, S- or R- 2-aryl propionic acid, there is also a need to make the synthetic process as efficient as possible.

Example 2 – Ibuprofen

Example 2.1 Resolution procedure

Racemic ibuprofen (530g) is dissolved in toluene (1335ml) and methanol (900ml).

The mixture is heated to dissolve the solid. S-1-Phenylethylamine (247g) is dissolved in toluene (200ml) and the solution is added with stirring at 600C over about 3 hours while the temperature is maintained at about 65-700C. The mixture is cooled gradually to 0 to 50C to induce crystallisation and stirred at this temperature for 1 hour. The crystals are filtered off, washed with toluene (600ml) and dried in a Vacuum oven at 550C to form crude S-ibuprofen / S-1-phenylethylamine salt (635g).

Crude S-ibuprofen / S-1-phenylethylamine salt (635g) is stirred with toluene (1930ml) and methanol (800ml) and the mixture is heated to 6O0C to dissolve the solid. The solution is cooled gradually to 0 to 5°C to induce crystallisation. The crystals are filtered off and dried in a vacuum oven at 55°C to form pure S-ibuprofen / S-I- phenylethylamine salt (510g). This recrystallisation of the S-ibuprofen / S-I- phenylethylamine salt may be repeated if necessary to upgrade the enantiomeric purity if required.

Pure S-ibuprofen / S-1-phenylethylamine salt (485g) is mixed with toluene (1700ml) with stirring. Water (300ml) and concentrated hydrochloric acid (17Og) are added and

÷ibe mixture is stirred at 600C. The lower aqueous layer is separated off and the upper organic layer is retained. The hydrochloric acid wash is repeated, then the toluene solution is washed with water. Water (370ml) and 47% sodium hydroxide

Figure imgf000023_0001

(118g) are added and the solution is heated to 600C and allowed to settle. The lower aqueous layer is separated and the upper toluene layer is washed with water. The aqueous phases are combined and heptane (420ml) is added. Hydrochloric acid

(130g) is added and the mixture is heated to 600C, stirred and settled. The organic layer is separated off and washed with water. The solution is cooled to -100C to induce crystallisation and the crystals are separated off by filtration, washed with heptane and dried under vacuum to yield (S)-ibuprofen (28Og) at an enantiomeric purity of over 99%.

Example 2.2 Racemisation procedure

Toluene/methanol mother liquors from the filtration of crude S-ibuprofen / S-I- phenylethylamine salt in the resolution procedure (2400ml, containing an estimated 130g of ibuprofen) is charged into a 3 L 3 necked round bottomed flask and methanol and toluene are distilled out at atmospheric pressure (volume removed approximately 1400 ml). The batch is then cooled to around 60°C and washed twice with hydrochloric acid (20 ml concentrated hydrochloric acid in 200 ml of water), and then twice with water (200 ml). Toluene is charged (80 ml) followed by methanol (200 ml) and caustic soda solution (45Og of 28% w/w solution, 5 molar equivalents). The mixture is heated to reflux for about 6 hours. Solvent is then removed at atmospheric pressure until the vapour temperature reaches approximately 85°C. The mixture is cooled to around 60°C and concentrated hydrochloric acid is charged at about 60 to 70°C until the pH of the mixture is 1 or less. The layers are allowed to separate and the bottom aqueous layer removed. The organic layer is washed with water (200 ml) and then azeotroped to dryness using a Dean and Stark trap. A solution of racemic ibuprofen in toluene remains.



Preparation of R – (+) _ flurbiprofen:

 The racemic flurbiprofen as a starting material, to obtain an intermediate product of formula I as shown and then the ester prepared as shown in Formula II with 5-isosorbide monobenzyl ether, ester hydrolysis after obtained R – (+) – flurbiprofen;

Figure CN104478703AD00061

wherein, in formula I, X is Cl or Br;

(2) by the R – (+) _ flurbiprofen obtained (RS) – flurbiprofen:

 The R _ (+) _ flurbiprofen 200mg, potassium hydroxide 150mg, 0. 5mL water into IOmL reaction flask and heated to 120 ° C and held for 2h, then water was added 15mL, cooled to room temperature, the resulting stirring the mixed solution with 10% hydrochloric acid to pH = 0. 5, extracted with ethyl acetate, combined several layers, washed with water until neutral, the organic solvent is recovered, the resulting residue was added at 60~90 ° C under an appropriate amount of petroleum ether by recrystallization, obtained (RS) – flurbiprofen 100mg, 50% yield.

 (3) Preparation of (S) -⑴- flurbiprofen:

 In 25mL single-necked flask, followed by adding (RS) – flurbiprofen 123mg, Portugal TOA 29. 8mg, isopropanol lmL, the mixture was stirred at reflux until clear, half the amount of the solvent evaporated under reduced pressure except , set the refrigerator overnight. The precipitate was collected by suction filtration as white crystals, after washing a small amount of isopropanol, which was dissolved in water, washed with 10% aqueous sodium hydroxide (10% NaOH mean mass fraction) adjusted pH = 13, the sheet-like precipitate was filtered off Portuguese octylamine white crystals. The resulting filtrate was added dropwise with stirring 10% hydrochloric acid to pH = 1, extracted with ethyl acetate, the organic layer was washed with water to recover the solvent, the resulting residue was purified by an appropriate amount of petroleum ether and recrystallized at 60~90 ° C. The product was collected by filtration, and dried in vacuo to give a white (S) – (+) _ flurbiprofen needle crystal 45. 3mg, 65% yield, mp 102~103 ° C, [α] = + 44 ° (C = 1, methanol), ee value of 92.6% (ee value measurement method: (S) – (+) – flurbiprofen after chiral amine derivatization reagents, by HPLC analysis).

wherein in step (3) is a byproduct eleven R _ (+) _ flurbiprofen, its follow step (1) of racemic reused.

 Step (1) of the specific operation is as follows:

 (la) 1:. Synthesis of 2,6-sorbitol dehydration -D- -5- benzyl ether: 4: 3

 250ml volumetric flask isosorbide 18. 25g (125mmol), lithium hydroxide monohydrate 5. 25g (125mmol) and 60ml of dimethyl sulfoxide (DMSO), heated to 90 ° C, stirred for 30min, constant pressure equalizing dropping funnel was added dropwise benzyl chloride 14. 4ml (125mmol), 90 ° C the reaction 19-20h, reaction mixture was adjusted to pH 1 with 2M hydrochloric acid, extracted with ethyl acetate (50ml * 3), the organic layers combined, washed with water ( 30ml * 2), dried over anhydrous sodium sulfate overnight, filtered and concentrated residue Cheng baby gel column chromatography (petroleum ether: ethyl acetate = 5: 1) to give a cream solid, that is 1: 4: 3: 2,6 Dehydration -D- sorbitol -5- benzyl ether 24. 5g, m.p. 59 ~61 ° C.

 (Ib) · 2- (2- fluoro-4-biphenylyl) propionyl chloride Synthesis

 50ml vial before racemic flurbiprofen was added 2. 44g (IOmmol), anhydrous toluene 20ml, freshly distilled thionyl chloride was added dropwise 0. 8ml (Ilmmol), N, N- dimethylformamide amide (DMF) 2 dropwise, stirred at room temperature 2h, the solvent was distilled off under reduced pressure to give a pale yellow gum, i.e., 2- (2-fluoro-4-biphenylyl) propionyl chloride, it was used directly in the reaction without isolation.

 (lc). R-2- (2- fluoro-4-biphenylyl) propionic acid 5- isosorbide monobenzyl ether ester synthesis

 The (Ib) resulting acid chloride was dissolved in 20ml of dry toluene was added dropwise at room temperature, dimethyl amine 3. 5ml, solid precipitation, stirred for about Ih, ice salt bath, a bath temperature of minus 10-15Ό, stirred at this temperature IOmin so, and then the constant pressure dropping funnel (Ia) 5 isosorbide monobenzyl ether (2. 83g, 12mmol) in toluene, keeping the reaction temperature, stirring 8h. The ice bath was removed and the reaction mixture under reduced pressure to remove the solvent, the residue was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate overnight, ethyl acetate was removed under reduced pressure, the residue was a white gel, recrystallized from petroleum ether to give a white solid that R-2- (2- fluoro-4-biphenylyl) propionic acid 5- isosorbide monobenzyl ether ester 3. 65g (7. 88mmol), in order to put the racemic flurbiprofen yield based on 78.8%.

(ld) R – Synthesis of flurbiprofen – (+)

 Under ice bath (Ic) obtained R-2- (2- fluoro-4-biphenylyl) propionic acid monobenzyl ether isosorbide 5- ester 2. 3Ig (5mmol) was dissolved in 20ml of acetone / water (1/1) was added Iml hydrochloric acid to adjust pH to 3, stirred for 3-4h, the reaction solution was extracted with ethyl acetate (20ml * 2), sash organic layer was washed with ice (10ml * 2), dried over anhydrous sodium sulfate overnight , filtration, and the filtrate was concentrated, the residue was recrystallized from ether to give white crystals, i.e. L-flurbiprofen 1.02g (4 18mmol.), yield 83.5%, optical purity 93% (HPLC method); input-racemic flurbiprofen dollars, the total yield of 78.8% * 83.5% = 65.8%.

 Step (1) reaction of the formula:

Figure CN104478703AD00071
3-Fluoro-4-phenyl-α-methylphenylacetic acid 1
M.p. 110-113°C (lit.3d 111-113.5°C).
1 H NMR (CDCl3, δ ppm) 7.51-7.55 (m, 2H), 7.49-7.37 (m, 4H), 7.21-7.16 (m, 2H), 3.85-3.78 (q, 1H, J = 7.1 Hz, CH), 1.60-1.57 (d, 3H, J = 7.1 Hz, CH3);
13C NMR (CDCl3 δ ppm) 180.4 (COOH), 161.3 & 158.0 (3-Ar-C), 140.9 & 140.8, 135.4, 130.9 & 130.8 (5-Ar-C), 128.9, 128.4, 128.2 & 128.0 (4-Ar-C), 127.7 (4′-Ar-C), 123.7 & 123.7 (6-Ar-C), 115.5 & 115.2 (2-Ar-C), 44.8 (CH), 18.0 (CH3).
 (d) Sagami Chemical Research Center. Jpn. Kokai Tokkyo Koho JP 8216840, 1982 (Chem. Abstr. 1982, 97: 5996s).
CAS : 5104-49-4
: 2-Fluoro-a-methyl[1,1¢-biphenyl]-4-acetic acid
Additional Names: 2-(2-fluoro-4-biphenylyl)propionic acid; 3-fluoro-4-phenylhydratropic acid
Manufacturers’ Codes: BTS-18322; U-27182
Trademarks: Adfeed (Lead Chem.); Ansaid (Pfizer); Antadys (Thžamex); Cebutid (Boots); Froben (Boots); Flurofen (Boots); Ocufen (Allergan); Stayban (Boots); Zepolas (Mikasa)
Molecular Formula: C15H13FO2
Molecular Weight: 244.26
Percent Composition: C 73.76%, H 5.36%, F 7.78%, O 13.10%
Literature References: Prepn: FR M5737; Adams et al., US 3755427 (1968, 1973 both to Boots Co., Ltd.). Pharmacology: Chalmers et al., Ann. Rheum. Dis. 31, 319 (1972); ibid. 32, 58 (1973); Glenn et al., Agents Actions 3, 210 (1973); Nishizawa et al.,Thromb. Res. 3, 577 (1973). HPLC determn in urine and plasma: J. M. Hutzler et al., J. Chromatogr. B 749, 119 (2000). Symposium on pharmacokinetics and clinical efficacy in pain management: Am. J. Med. 80, Suppl. 3A, 1-157 (1986).
Properties: Crystals from petr ether, mp 110-111°. Slightly sol in water (pH 7.0); readily sol in most polar solvents.
Melting point: mp 110-111°
Therap-Cat: Anti-inflammatory; analgesic.

Flurbiprofen NMR spectra analysis, Chemical CAS NO. 5104-49-4 NMR spectral analysis, Flurbiprofen C-NMR spectrum

Flurbiprofen NMR spectra analysis, Chemical CAS NO. 5104-49-4 NMR spectral analysis, Flurbiprofen H-NMR spectrum

 s form
 (S)-Flurbiprofen NMR spectra analysis, Chemical CAS NO. 51543-39-6 NMR spectral analysis, (S)-Flurbiprofen H-NMR spectrum
 (S)-Flurbiprofen NMR spectra analysis, Chemical CAS NO. 51543-39-6 NMR spectral analysis, (S)-Flurbiprofen C-NMR spectrum
Patent Submitted Granted
Methods to accelerate the isolation of novel cell strains from pluripotent stem cells and cells obtained thereby [US2008070303] 2006-11-21 2008-03-20
Herpes Virus-Based Compositions and Methods of Use in the Prenatal and Perinatal Periods [US2008226601] 2006-06-05 2008-09-18
METHOD OF REDUCING ABETA42 AND TREATING DISEASES [US2008021085] 2007-06-21 2008-01-24
Pyridyl Amide T-Type Calcium Channel Antagonists [US2011112064] 2011-05-12
Patent Submitted Granted
Nitroxyderivatives having antinflammatory, analgesic and antithrombotic activity [US6613784] 2003-09-02
Global method for mapping property spaces [US6675136] 2004-01-06
Method of reducing Abeta42 and treating diseases [US2006004086] 2006-01-05
11-Beta-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia [US7179802] 2004-06-03 2007-02-20
Process for producing optically active flurbiprofen [US7214820] 2006-06-22 2007-05-08
Pyridyl Amide T-Type Calcium Channel Antagonists [US7875636] 2009-11-05 2011-01-25
(R)-2-(3-Benzoylphenyl)propionic acid salts and pharmaceutical preparations containing them [EP0935961] 1999-08-18 2008-04-02

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

Taisho Pharmaceutical Co., Ltd. (大正製薬株式会社 Taishō Seiyaku Kabushiki-gaisha?) (TYO: 4535) is a Japanese pharmaceutical company based in Tokyo.



Map of tirupati town.
Clockwise from top: Tirumala Venkateswara Temple, Tirumala ghat road, City skyline and Chandragiri fort

Clockwise from top: Tirumala Venkateswara Temple, Tirumala ghat road, City skyline and Chandragiri fort

Tirupati is located in Andhra Pradesh


Location in Andhra Pradesh, India

Coordinates: 13.65°N 79.42°ECoordinates: 13.65°N 79.42°E
Country India
State Andhra Pradesh
Region Rayalaseema
District Chittoor
 • Member of Parliament Varaprasad Rao Velagapalli
 • City 24 km2 (9 sq mi)
Elevation 161 m (528 ft)
Population (2011)[1]
 • City 287,035
 • Density 12,000/km2 (31,000/sq mi)
 • Metro[2] 459,985
 • Official Telugu
Time zone IST (UTC+5:30)
PIN 517501
Telephone code +91–877
Vehicle registration AP 03
Website Tirupati Mucnicipal Corporation


Kapila Theertham in Tirupati

Food Service During Tirumala Tirupati Devastanam’s ‘Srinivasa Kalyanam Utsavam’ at MARG Swarnabhoomi



Harbin Gloria to Commercialize Constipation Drug in China

Harbin Gloria to Commercialize Constipation Drug in China

Harbin Gloria Pharma in-licensed China rights to Amitiza, a novel anti-constipation drug from Sucampo Pharma of the US. Amitiza is a chloride channel activator, approved for US use in 2006, which acts in the small intestine. Gloria will be responsible for obtaining CFDA approval of the drug and then commercializing it in China. Gloria paid $1 million upfront and will be liable for additional milestone payments. More details….

– See more at:

AMITIZA (lubiprostone)



Harbin Gloria Pharmaceuticals Co., Ltd. engages in the research, development, production, and sale of pharmaceutical products primarily in the People’s Republic of China. The company offers orthopedic medicines, antineoplastic products, medical-nutrition products, rheumatology drugs, digestive and respiratory system medicines, cardiovascular medicines, liver disease medications, gynecology medications, and antibiotics. It also provides circulatory system, pediatrics, uropoiesis and reproduction, immune regulation, and other products. Harbin Gloria Pharmaceuticals Co., Ltd. was founded in 2000 and is based in Harbin, the People’s Republic of China.

No. 29, Beijing Road

Limin Economic & Technological Development Zone

Harbin,  150025


Founded in 2000


86 451 5735 1368


86 451 5735 1992


Map of harbin china






Lascufloxacin, KRP-AM1977, by Kyorin

Figure JPOXMLDOC01-appb-C000001

2D chemical structure of 848416-07-9


CAS 848416-07-9

Kyorin Pharmaceutical Co., Ltd., 杏林製薬株式会社

3-Quinolinecarboxylic acid, 7-((3S,4S)-3-((cyclopropylamino)methyl)-4-fluoro-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-

7-((3S,4S)-3-((Cyclopropylamino)methyl)-4-fluoropyrrolidin-1-yl)-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

{(3S, 4S) -3 – [(cyclopropylamino) methyl] -4-fluoro-1-yl} -6-fluoro-1- (2 – fluoroethyl) -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid



  • C21-H24-F3-N3-O4
  • 439.4316
  • SMILES……COc1c2c(cc(c1N3C[C@H](C(C3)CNC4CC4)F)F)c(=O)c(cn2CCF)C(=O)O


Lascufloxacin hydrochloride

2D chemical structure of 1433857-09-0

  • C21-H24-F3-N3-O4.Cl-H
  • 475.8925
  • CAS 1433857-09-0

3-Quinolinecarboxylic acid, 7-((3S,4S)-3-((cyclopropylamino)methyl)-4-fluoro-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-, hydrochloride (1:1)


Lascufloxacin mesylate2D chemical structure of 1433857-41-0

3-Quinolinecarboxylic acid, 7-((3S,4S)-3-((cyclopropylamino)methyl)-4-fluoro-1-pyrrolidinyl)-6-fluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-, methanesulfonate (1:1)

  • C21-H24-F3-N3-O4.C-H4-O3-S
  • 535.5372
  • CAS 1433857-41-0

The other non-fluorinated quinolone under clinical development is KRP-AM1977, by Kyorin, which is in Phase I of clinical trials. The oral formulation of the compound (KRP-AM1977X) is being tested for treatment of respiratory infections and the I.V. formulation is under development for treatment of MRSA infections [1,2].



WO 2013069297

The present invention is represented by Formula (1) – {(3S, 4S) -3 – [(cyclopropylamino) methyl] -4-fluoro-1-yl} -6-fluoro-1- (2 – fluoroethyl) -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (hereinafter, compound (1) crystals of a salt also referred to), and a method for their preparation.

Figure JPOXMLDOC01-appb-C000001

Typically, the pharmaceutical, in addition to the therapeutic effects on diseases, such as safety and quality are required. Therefore, the compound is the active ingredient of drugs, a variety of conditions and that is excellent in storage stability in the (light, temperature, humidity etc. influence the compound) are determined. Also, if the medicament is a dosage form such as oral preparations and injections, it is preferred that higher solubility in active ingredients of the water contained.

Compound (1) is safe, not only exhibit a strong antimicrobial action, conventional hard Gram-positive bacteria antimicrobial agents shown efficacy, particularly MRSA, PRSP, to VRE such resistant strains, to exhibit strong antibacterial activity It is known (for example, Patent Document 1).

WO 2005/026147

Patent Document 1, as the physicochemical characteristics of the compound (1) only has been shown to be a light brown free crystals. Also, Patent Document 1, the solubility in water of Compound (1), stability, no disclosure whatsoever information including characteristics of the crystal.
The present invention aims to provide a technique capable of improving the solubility and storage stability in water of the compound (1).

(Reference Example 4)
Bis (acetato -O) – [6,7-difluoro-1- (2-fluoro-ethyl) -8-methoxy-4-oxo-1,4-dihydro-3-carboxylate -O 3, O 4] boron Under a nitrogen atmosphere, boric acid (catalyst preparation) 86.4 g (1.40mol) was added acetic anhydride 17.9 L (190mol), and was heated and stirred for 30 minutes at 70.0 ~ 77.7 ℃. It was then cooling the mixture to an internal temperature of 24.7 ℃ (hot water set temperature 23.0 ℃). Subsequently, it was added portionwise boric acid to 4 times to the mixture. Specifically, the addition of boric acid (1 time) 842g of (13.6mol) to the mixture and stirred for 30 minutes at 24.7 ~ 27.4 ℃. The addition of boric acid (second) 842g of (13.6mol) to the mixture and stirred for 30 minutes at 24.3 ~ 26.3 ℃. In addition boric acid (third time) 842g the (13.6mol) to the mixture, and the mixture was stirred for 30 minutes at 24.3 ~ 26.8 ℃. In addition boric acid (4 th) 842g the (13.6mol) to the mixture, and the mixture was stirred for 30 minutes at 25.1 ~ 28.3 ℃. The mixture was stirred for 30 minutes at 50.0 ~ 54.9 ℃, was with boric acid triacetate adjusted solution.
In the boric acid triacetate adjusted solution, 6,7-difluoro-1- (2-fluoro-ethyl) -8-methoxy-4-oxo-1,4-dihydro-3-carboxylic acid ethyl ester 4.60kg (14. In a reaction preparation solution are added 0mol), and stirred for 3 hours at 53.7 ~ 56.9 ℃. The reaction preparation was cooled to 30.0 ℃, and allowed to stand overnight at room temperature. The reaction preparation was allowed to dissolve with heating to precipitate up to 55.0 ℃, acetone 13.8L was added and the reaction solution (1).
Separately, under nitrogen atmosphere, it is mixed Tsunemizu 161L and aqueous ammonia (28%) 28.2L (464mol), and cooled the mixture to 1.6 ℃. To the mixture, it was added the reaction solution of the above (1), to obtain a crude crystal acquisition solution crowded washed with acetone 9.20L. After cooling the crude crystal acquisition solution to 15.0 ℃, it was stirred for 1 hour at 6.2 ~ 15.0 ℃. And The precipitated crystals were filtered, washed with Tsunemizu 46.0L, to give 9.07kg of wet crude crystals. Set temperature 65.0 to about 16 hours and dried under reduced pressure at ℃, the crude crystals were obtained 5.89kg.
Under a nitrogen atmosphere, it is mixed acetone and 29.5L crude crystal, the resulting mixture was heated and dissolved (melting temperature 52.6 ℃). When heated, it was dropped until the crystallization of diisopropyl ether 58.9L in a mixture (dropping amount 10.0L; 52.8 → 48.7 ℃; crystallization temperature 49.0 ℃). After crystallization confirmation, stirred for 15 minutes the mixture at 49.0 ~ 50.1 ℃, it was dropped the rest of diisopropyl ether to the mixture (50.1 → 46.4 ℃), 46.7 ~ 51.7 It was stirred for 15 minutes mixture at ℃. After cooling the mixture to 15 ℃, it was stirred for 30 minutes at 8.1 ~ 15.0 ℃. And The precipitated crystals were filtered, washed with acetone and diisopropyl ether 5.89L 11.8L, to obtain 6.19kg of wet crystals. For about 20 hours drying under reduced pressure at warm water set temperature 65.0 ℃, bis (acetato -O) – [6,7-difluoro-1- (2-fluoroethyl) -8-methoxy-4-oxo-1,4- dihydro-3-carboxylate -O 3, O 4] was obtained 5.42kg boron (90.4% yield).

Melting point: 183 ~ 185 ℃ (dec).
Elemental analysis (%): calculated as C 17 H 15 BF 3 NO 8: C, 47.58; H, 3.52; N, 3.26.
Measured value: C, 47.91; H, 3.44; N, 3.04.
1 H-NMR (CDCl 3, 400 MHz) δ: 2.04 (6H, s), 4.22 (3H, d, J = 2.4Hz), 4.88 (2H, dt, J = 47.0 , 4.4Hz), 5.21 (2H, dt, J = 24.9,4.4Hz), 8.17 (1H, t, J = 8.8Hz), 9.11 (1H, s).
ESI MS (positive) m / z: 430 (M + H) +.
IR (KBr) cm -1: 3080,1703.


WO 2005026147


3-Pyrrolidinemethanamine,N-cyclopropyl-4-fluoro-,(3R,4S)-(9CI) Structure


3-​Pyrrolidinemethanami​ne, N-​cyclopropyl-​4-​fluoro-​, (3R,​4S)​-

3-Pyrrolidinemethanamine, N-cyclopropyl-4-fluoro-, (3R,4S)- Chemical Name:3-Pyrrolidinemethanamine, N-cyclopropyl-4-fluoro-, (3R,4S)-CAS: 604798-54-1Molecular Formula: C8H15FN2Molecular Weight: 158.2165032
Chemical Name: 3-Pyrrolidinemethanamine, N-cyclopropyl-4-fluoro-, (3R,4S)-
CAS: 604798-54-1
Molecular Formula: C8H15FN2
Molecular Weight: 158.2165032



CAS 848498-67-9

Boron, bis(acetato-​κO)​[6,​7-​difluoro-​1-​(2-​fluoroethyl)​-​1,​4-​dihydro-​8-​methoxy-​4-​(oxo-​κO)​-​3-​quinolinecarboxylato​-​κO]​-​, (T-​4)​-
Coordination Compound
化学物質名 ビス(アセチルオキシ)[6,7-ジフルオロ-1-(2-フルオロエチル)
構造別分類コード番号 F60622212422


安衛法官報通し番号 21534
安衛法官報公示整理番号 8-(1)-3764
安衛法官報公示時期 平成24年9月27日
CAS番号 848498-67-9
出典 厚生労働省



3-Quinolinecarboxylic acid, 6,7-difluoro-1-(2-fluoroethyl)-1,4-dihydro-8-methoxy-4-oxo-, ethyl ester



化学物質名 6,7-ジフルオロ-1-(2-フルオロエチル)-8-メトキシ-4-オキ
構造別分類コード番号 F60622322422


安衛法官報通し番号 21467
安衛法官報公示整理番号 8-(1)-3758
安衛法官報公示時期 平成24年9月27日
CAS番号 114214-60-7
出典 厚生労働省
WO2003076428A1 * 8 Mar 2002 18 Sep 2003 Toshifumi Akiba Quinolonecarboxylic acid derivative
WO2005026147A1 8 Sep 2004 24 Mar 2005 Yoshikazu Asahina 7-(4-substituted 3- cyclopropylaminomethyl-1­ pyrrolidinyl) quinolonecarboxylic acid derivative
WO2007082471A1 * 18 Jan 2007 26 Jul 2007 Guangzhou Baiyunshan Pharmaceu Anti-infective compound, preparation method thereof and use thereof
CN1158846A * 9 May 1995 10 Sep 1997 昆山市康壮达兽药厂 Synthesis technology of norfluxacini hydrochloride
WO2014174846A1 * 24 Apr 2014 30 Oct 2014 Kyorin Pharmaceutical Co., Ltd. Solid pharmaceutical composition
WO2014174847A1 * 24 Apr 2014 30 Oct 2014 Kyorin Pharmaceutical Co., Ltd. Solid pharmaceutical composition
WO2014174848A1 * 24 Apr 2014 30 Oct 2014 Kyorin Pharmaceutical Co., Ltd. Tablet
  1. Kyorin. Kyorin—Main R&D Activities-1 (4 February 2013 Release). Available online: (accessed on 4 February 2013).
  2. Kyorin. Drug discovery, development, and lcm with medical professionals and patients in mind. Available online: (accessed on 11 April 2013).



KYORIN Pharmaceutical Co., Ltd. - Your health is Kyorin's mission.

Mitsutomo Miyashita, Representative Director, President and Chief Executive Officer

Mitsutomo Miyashita

  • KYORIN Co,.Ltd.

Access Map

Ochyanomizu Sola City 16F,
Kanda Surugadai 4-6, Chiyoda-ku,
Tokyo 101-8311 Japan
TEL: 03-3525-4711

One-minute walk from the Hijiribashi exit of Ochanomizu station on JR Chuo and Sobu lines
One-minute walk from the B2 exit of Shin-Ochanomizu station on Tokyo Metro Chiyoda line
Four-minutes walk from the No.1 exit of Ochanomizu station on Tokyo Metro Marunouchi line
Six-minutes walk from the B3 exit of Ogawamachi station on Toei Subway Shinjuku line


Company Profile

Trade Name KYORIN Pharmaceutical Co.,Ltd.
Business Manufacture and sales of prescription medicines
Head Office Ochyanomizu Sola City 16F,
Kanda Surugadai 4-6, Chiyoda-ku,
Tokyo 101-8311 Japan (Access Map)
Telephone 03-3525-4711
Foundation 1923
Establishment 1940
Shimotsuga-gun, Tochigi
Map of shimotsuga district
Tochigi Wanpaku Park – Mibu-machi – Reviews of Tochigi Wanpaku Park –
Ochanomizu station

Lupin buys Brazilian pharmaceutical firm Medquímica


Lupin buys Brazilian pharmaceutical firm Medquímica
India-based drugmaker Lupin has acquired 100% equity interest in Brazilian pharmaceutical firm Medquímica Indústria Farmacêutica.

read at

Group president and CEO, Lupin Pharmaceuticals, and director on the board of Lupin Limited, Vinita Gupta



A Medquímica Indústria Farmacêutica é uma empresa genuinamente brasileira que atua na produção de medicamentos para o uso humano. Com sua linha de produção instalada em Juiz de Fora, a Medquimica está presente em todo o Brasil através de seus representantes.

Working in syntony with the market. There are 30 years that it is the north that takes the Medquímica Pharmaceutical Industry Ltda. to dedicate to the production of pharmaceutical products of proven effectiveness and certain return for all its net of customers. For such, the Medquímica invests in physical and human resources, forming a qualified and highly experienced technical team, who detaches in the marketplace for producing medicines of uncontestable quality and trustworthiness.

With the quality certified through the Good Practical of Manufacture, the Medquímica detaches for having a laboratory of reference inside its installations. Moreover, respecting the resolution 134 from Anvisa, gradually, all its medicines are being evaluated for the tests of pharmaceutical equivalence, proving, in this way, the quality of Medquímica’s product. Such actions had resulted in a supported growth of credibility and sales.

For giving support to all this development, the Medquímica will start the construction of the first projected national plant in the most rigorous and recent requirements of the ANVISA. Thirty years of history, qualified technician team, tests of equivalence and bioequivalência and a model plant makes from Medquímica the certain alternative for the success of its businesses

(32) 3224-4087 (Telefax)

(32) 2101-4000 (Telefax)

The Medquímica Pharmaceutical Industry is a genuinely Brazilian company that acts in the medicine production for the human use. With its line of production installed in Juiz de Fora, the Medquimica is present in all over Brazil through its representatives.

Rua Otacílio Esteves da Silva, 40
Bairro Granjas Betânia
CEP: 36047-400
Juiz de Fora – MG

Rua Fernando Lamarca, 255
Bairro Distrito Industrial
CEP: 36092-030
Juiz de Fora – MG

Juiz de Fora

Map of juiz de fora

Paço Municipal de Juiz de Fora


No todo parece bem interessante. Dá pra tirar muitas fotos boas. Já teve outro thread bem legal sobre a cidade.






CARMEN DRAHL….Tribute to a Great Writer


Award-winning science communicator and social media power user based in Washington, DC.

Carmen Drahl is a multimedia science journalist and chemistry communicator based in Washington, DC.

A social media evangelist, Carmen started her first chemistry blog in 2006. Today, she regularly leverages Twitter, Facebook, and Google Plus Hangouts in her reporting.

Carmen has written about how life may have originated on Earth, explained how new medications get their names, and covered the ongoing issues plaguing the forensic science community. Her video on the food science behind 3D printed cocktail garnishes won the 2014 Folio Eddie Award for Best Association Video.

Until December 2014, Carmen worked at Chemical & Engineering News magazine. Her work has also been featured at Scientific American’s blog network, SiriusXM’s Doctor Radio, and elsewhere.

Carmen holds a Ph.D. in chemistry from Princeton University.


interviewing, science writing, social media, Twitter, Storify, YouTube,
public speaking, hosting, video production, iPhone videography,
non-linear video editing, blogging (WordPress and Blogger), HTML website

We have been reading her for the past several years and a inspiration for many

Carmen Drahl - Science Communicator



Carmen Drahl (@carmendrahl) | Twitter

Carmen Drahl – Google+

Carmen Drahl



Princeton University

Ph.D., Chemistry

2002 – 2007

Ph.D. with Erik J. SorensenShe was on a team that completed the first total synthesis of
abyssomicin C, a molecule found in small quantities in nature that
showed hints of promise as a potential antibiotic. I constructed
molecular probes from abyssomicin for proteomics studies of its
biological activity.

M.A. with George L. McLendon

toward developing a drug conjugate as a potential treatment for cancer. I
synthesized a photosensitizer dye-peptide conjugate for targeting the
cell death pathway called apoptosis.


At a reception before the Alumni Day luncheon, President Tilghman (third
from left) congratulated the winners of the University’s highest awards
for students: (from left) Pyne Prize winners Lester Mackey and Alisha
Holland; and Jacobus Fellowship recipients Sarah Pourciau, Egemen
Kolemen and Carmen Drahl. Unable to attend the event was Jacobus Fellowship winner William Slauter. (photo: Denise Applewhite

B.A., Chemistry

1998 – 2002

summa cum laude with specialized honors in chemistry. Honors thesis
entitled “Structural, kinetic, and mechanistic studies: the protein
tyrosine phosphatases CD45 and PTP1B”
Activities and Societies: Phi Beta Kappa

  Carmen Drahl, Class of 2002,



Science Journalist


January 2014 – Present Washington D.C. Metro Area

science journalist – I deliver clean products on time. Experience in
reporting on chemistry, food science, history of science, drug
development, science education.

Senior Editor, Chemical & Engineering News

American Chemical Society

August 2007 – December 2014 (7 years 5 months)Washington D.C. Metro Area

Reporting:Cover the science of chemistry for C&EN, the American Chemical
Society’s weekly magazine, circulation 160,000. Track new research
findings daily, particularly in forensic science, drug discovery,
organic chemistry, and food science.


Doubled circulation to C&EN’s YouTube channel in 2013. Scripted, narrated, edited footage.

Managed a core team of 4 and collaborated with other reporters to
produce 30 videos, some reproduced in The Atlantic, Scientific American,
Eater National, The Daily Mail.

Incepted, scripted, and co-hosted
“Speaking of Chemistry”, a monthly web show that summarizes top
chemistry news for the busy scientist.

Social Media:

Developed magazine-wide best practices for YouTube videos and Twitter. Ran staff workshops about Storify, Slashdot, and Reddit.

Hosting/Public Speaking:

Topics include communicating chemistry simply, transitioning from a
Ph.D. to careers in science communication. Moderated discussions on
chemophobia, social media usage in the chemical sciences. On-camera
co-host for web newscasts produced by ACS.


C&EN art and web teams, developed first-for-the-magazine features,
including a 90th anniversary commemorative timeline poster, a pullout
guide to top conference speakers, interactive quizzes and database

Carmen Drahl, senior editor of Chemical and Engineering News,
used her Ph.D. in chemistry as a springboard into the career she
envisioned for herself. Here she shares some advice that helped her make
the decision.

Carmen Drahl made the transition to a writing
career while earning a Ph.D. in chemistry at Princeton University. Born
and raised in New Jersey, she now lives in Washington, D.C., and reports
for Chemical and Engineering News (C&EN). At C&EN
she has written about how new medications get their names, explained
the science behind a controversial hair-straightening product, and
covered the scientific firestorm sparked by an alleged arsenic life
form. Her work has been featured on SiriusXM’s Doctor Radio, Radio New Zealand’s This Way Up, and elsewhere. Her coverage has also been recognized by MIT’s Knight Science Journalism Tracker.

(Open)1 honor or award
Scientific Cocktails: Award-winning video
Scientific Cocktails: Award-winning video
Speaking of Chemistry: All About Tinsel
Speaking of Chemistry: All About Tinsel

Carmen Drahl

Twitter Maven

World Central Kitchen

March 2013 – August 2014 (1 year 6 months)Washington D.C. Metro Area

she was the “voice of Twitter” for World Central Kitchen, the humanitarian
organization founded by renowned Chef José Andrés. Doubled followers to
Twitter account in 2013, developed Twitter strategy for projects and
events. Edited Annual Report, press releases and other communication
materials. Volunteered in person at outreach events.

Contributing Editor, AWIS Magazine

Association of Women in Science

December 2005 – August 2007 (1 year 9 months)

reported and wrote profiles of prominent women scientists in a range of
fields (molecular biology, physics, geoscience) for the Research
Advances column in AWIS Magazine.

Writer, various publications

Princeton University

April 2005 – May 2007 (2 years 2 months)

reported and wrote news for the Princeton University News Office’s
Research Notes, and wrote news and features for the Princeton University
Chemistry Department’s Industrial Affiliates Program Newsletter and
Chemistry Alumni Newsletter.

Honors & Awards

Eddie Digital Award- Best Video (B-to-B)

FOLIO Magazine

December 2014

Porter Ogden Jacobus Fellowship

Princeton University

February 2007

NSF Graduate Research Fellowship

National Science Foundation


Volunteer Experience & Causes

Board Member

Princeton Alumni Weekly Magazine

October 2013

Advisory Committee

American Institute of Physics News and Media Services

October 2013

Member, Graduate Alumni Leadership Council

Princeton University

2009 – 2012 (3 years)


Continuing with the tradition from last two years, I will occasionally post interviews with some of the participants of the ScienceOnline2010 conference that was held in the Research Triangle Park, NC back in January. See all the interviews in this series here. You can check out previous years’ interviews as well: 2008 and 2009.Today, I asked Carmen Drahl, Associate Editor for Science/Technology/Education at Chemical & Engineering News (find her as @carmendrahl on Twitter) to answer a few questions.Welcome
to A Blog Around The Clock. Would you, please, tell my readers a little
bit more about yourself? Where are you coming from (both geographically
and philosophically)? What is your (scientific) background?
i-b183f89fe33d3d9f0b308a6cb30d9b5b-Carmen Drahl pic1.JPGIt’s a pleasure and a privilege to be interviewed, Bora.Good
conversations make me happy. School was fun for me (well, maybe not
grad school) and that’s evolved into a desire to always be learning
something new. I enjoy doing nothing as much as I enjoy doing things. On
Mondays, if I’m not too busy, I take hip-hop dance classes.her hometown is Hackettstown, New Jersey. M&M’s are made there. I got a
bachelor’s in chemistry from Drew University and a Ph.D. in chemistry at
Princeton. Scientifically my expertise hovers somewhere around the
interface between organic chemistry and biochemistry. A short while
after defending my dissertation, I moved to Washington DC to write for Chemical & Engineering News, and that’s where I’ve been for almost three years now.When and how did you first discover science blogs?Scandal
led me to science blogs. Seriously. In March 2006 I was still an
organic chemistry grad student. Everyone in my lab was buzzing about a
set of retractions in the Journal of the American Chemical Society
(disclosure: today I work for the American Chemical Society, which
publishes JACS). A rising young organic chemistry star retracted the
papers because work by one of his graduate students couldn’t be
reproduced. It was a big deal and became an even bigger deal as the
inevitable rumors (salacious and otherwise) surfaced. The blogosphere
had the details first. So that’s where Google pointed me and the other
members of my lab when we searched for more information. I learned about
the awesome (but sadly now defunct) blogs Tenderbutton and The Endless
Frontier, by Dylan Stiles and Paul Bracher, both chemistry grad students
like me. I also discovered the solid mix of chemistry and pharma at
Derek Lowe’s In the Pipeline, which is still the first blog I visit every day.Tell us a little more about your career trajectory so far: interesting projects past and present?

i-b7bd4d4568d9689c2daf400303c886c3-Carmen Drahl pic2.JPGBy
the time I discovered science blogs I knew my career goals were
changing. I’d already been lucky enough to audit a science writing
course at Princeton taught by Mike Lemonick from TIME, and thought that
maybe science writing was a good choice for me. After reading chemistry
blogs for a while I realized “Hey, I can do this!” and started my own
blog, She Blinded Me with Science, in July 2006. It was the typical grad student blog, a mix of posts about papers I liked and life in the lab.

At C&E News I’ve contributed to its C&ENtral Science
blog, which premiered in spring 2008. I’ve experimented with a few
different kinds of posts- observations and on-the-street interviews when
I run into something chemistry-related in DC, in-depth posts from
meetings, and video demos of iPod apps. One of my favorite things to do
is toy with new audio/video/etc technology for the blog.

What is taking up the most of your time and passion these days? What are your goals?

In March I just started a new era in my web existence- I’m becoming a pharma blogger. I’m the science voice at The Haystack,
C&E News’s new pharma blog and one of seven new blogs the magazine
launched last month. My co-blogger is the talented Lisa Jarvis, who’s
written about the business side of pharma for ten years and who brings a
solid science background to the table as well. I kicked us off by
liveblogging/livetweeting a popular session at the American Chemical
Society’s meeting in San Francisco where drug companies reveal for the
first time the chemical structures of potential new drugs being tested
in clinical trials. The whole thing synced to FriendFeed as well. Folks
followed the talks from all three venues, which was great. I hope I can
continue doing that sort of thing in the future.

this August, I’m co-organizing a mini-symposium at the American
Chemical Society meeting in Boston about the chem/pharma blogosphere and
its impact on research and communication. I’m in the process of
inviting speakers right now. It’s my first time doing anything like this
and part of me is petrified that no one will show up. Tips on
organizing a conference session and how not to stress when doing so are

More broadly, I’d love to get more chemistry bloggers to
connect with the community that attends ScienceOnline. I don’t ever want
to become that old (or not-so-old) person who is clueless about
them-thar newfangled whosiwhatsits that the kids are using nowadays.

What aspect of science communication and/or particular use of the Web in science interests you the most?

few things come to mind, actually. I’d like to think that the web has
made grad school a helluva lot less isolating for science grad students.
You have the virtual journal clubs like Totally Synthetic, posts like SciCurious’s letter to a grad student, etc.

a journalist the web’s capacity to equalize fascinates me. I’m
extremely lucky to have a staff gig as a science writer without having
gone to journalism school or landed a media fellowhip and it’s weird to
think that my old blog might’ve helped my visibility. I didn’t know Ed
Yong’s story until Scio10 but I think he’s a highly talented example of
how the web can open doors.

The web’s equalizing power goes to
readers of science content as well as writers, of course. In the ideal
situation a reader can give a writer instant feedback and you can get a
real conversation going, something that was much harder with the
snail-paced system of letters to the editor and reader surveys. Not that
the conversation is always civil. Most of C&EN’s readers have a
decent amount of scientific training, but the debate that rages whenever
we run an editorial about climate change is as intense as any I’ve

In cases like that I don’t know that the web gives people a
good representation of what the consensus is. For folks who don’t have
scientific training, how do you ensure that people don’t just go to the
content that already confirms their pre-existing beliefs about autism or
global warming? John Timmer touched on this more eloquently in his interview with you,
and I agree with him that I don’t think we have an answer yet. Though
on a slightly different note, I will mention that I’ve been enjoying the
New York Times’s recent attempts to recapture the spontaneity of
flipping through the newspaper in online browsing, like the Times Skimmer for Google Chrome.

What are some of your favourite science blogs? Have you discovered any cool science blogs by the participants at the Conference?

In addition to the blogs I’ve already mentioned I enjoy Carbon-Based Curiosities, Wired Science, Chemistry Blog, and Terra Sigillata, to name a few of the 50 or so blogs on my feed reader.

I discovered scads of new blogs at Scio10 but I’ll focus on the one that’s become required reading for me these days: Obesity Panacea.
I’d covered obesity drug development for C&EN but I’d never met
Travis Saunders and Peter Janiszewski or heard of their blog until the

What was the best aspect of ScienceOnline2010 for
you? Is there anything that happened at this Conference – a session,
something someone said or did or wrote – that will change the way you
think about science communication, or something that you will take with
you to your job, blog-reading and blog-writing?

Dave Mungeris
my hero – his blogging 102 session was packed with practical tips that I
brought back to C&EN for incorporating into our blogs, such as the
use of the Disqus plugin for catching conversations on social networks,
getting smart about using stats and surveys, etc. Some of that’s already
happened, and some of the ideas are still in the works.

I came
for the nuts-and-bolts blogging tips but I stayed for the conversations,
especially the ones at the bar after the official program was done for
the night. And the icing on the cake was seeing folks I’d worked with
but never met, like Cameron Neylon and you, Bora, and catching up with
people I hadn’t seen in months, like Jean-Claude Bradley, Aaron Rowe,
Jennifer Ouellette and Nancy Shute.

It was so nice to meet you in person and thank you for the interview. I hope to see you again next January.

Company: GlaxoSmithKline

Meant to treat: tumors with loss-of-function in the tumor suppressor
protein PTEN (phosphatase and tensin homolog)- 2nd most inactivated
tumor suppressor after p53- cancers where this is often the case include
prostate and endometrial

Mode of action: inhibitor of
phosphoinositide 3-kinase-beta (PI3K-beta). Several lines of evidence
suggest that proliferation in certain PTEN-deficient tumor cell lines is
driven primarily by PI3K-beta.

Medicinal chemistry tidbits: The GSK
team seemed boxed in because in 3 out of 4 animals used in preclinical
testing, promising drug candidates had high clearance. It turned out
that a carbonyl group that they thought was critical for interacting
with the back pocket of the PI3K-beta enzyme wasn’t so critical after
all. When they realized they could replace the carbonyl with a variety
of functional groups, GSK2636771 eventually emerged. GSK2636771B (shown)
is the tris salt of GSK2636771.

Status in the pipeline: Phase I clinical trials……….


Posted By on Mar 24, 2012

Phone: 202-872-4502

Fax: 202-872-8727 or -6381

Company: GlaxoSmithKline

Meant to treat: tumors with loss-of-function in the tumor suppressor
protein PTEN (phosphatase and tensin homolog)- 2nd most inactivated
tumor suppressor after p53- cancers where this is often the case include
prostate and endometrial

Mode of action: inhibitor of
phosphoinositide 3-kinase-beta (PI3K-beta). Several lines of evidence
suggest that proliferation in certain PTEN-deficient tumor cell lines is
driven primarily by PI3K-beta.

Medicinal chemistry tidbits: The GSK
team seemed boxed in because in 3 out of 4 animals used in preclinical
testing, promising drug candidates had high clearance. It turned out
that a carbonyl group that they thought was critical for interacting
with the back pocket of the PI3K-beta enzyme wasn’t so critical after
all. When they realized they could replace the carbonyl with a variety
of functional groups, GSK2636771 eventually emerged. GSK2636771B (shown)
is the tris salt of GSK2636771.

Status in the pipeline: Phase I clinical trials……….


Posted By on Mar 24, 2012

Phone: 202-872-4502

Fax: 202-872-8727 or -6381

  1. Map of washington dc
Washington, D.C.



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