BS B2B Bureau | Mumbai April 12, 2016 Last Updated at 10:27 IST
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/////inhaler, Novartis Healthcare, Sequadra, indacaterol, glycopyrronium inhaler, Lupin, inhaler, brand name, Loftair, India
P7435
Piramal Enterprises Mumbai, India
P-7435; P7435-DGAT1, P7435, P 7435
| Latest Stage of Development | Phase I |
| Standard Indication | Metabolic (unspecified) |
| Indication Details | Treat metabolic disorders |
https://clinicaltrials.gov/ct2/show/NCT01910571
https://clinicaltrials.gov/ct2/show/NCT01764425
Chairman Ajay Piramal
Nandini Piramal, Executive Director, Piramal Enterprises
http://www.pharmabiz.com/NewsDetails.aspx?aid=76992&sid=2
Our Bureau, Mumbai
Tuesday, August 06, 2013, 12:25 Hrs [IST]
Piramal Enterprises Ltd has received US Food and Drug Administration (FDA) approval for its Investigational New Drug (IND) P7435. This is a novel, potent and highly selective, oral diacylglycerolacyltransferase 1 (DGAT1) inhibitor.
P7435 has been developed by the NCE Research Division of PEL for the management of metabolic disorders such as lipid abnormalities and diabetes. It is well-established that increased lipid levels’ (including triglycerides) is one of the major risk factors for cardiovascular disease (CVD). It has been reported by the World Health Organisation, that CVD, is the number one cause of deaths globally, representing approximately 30 per cent of all deaths. Currently, there is a significant medical need for effective and safe drugs for the management of lipid abnormalities and metabolic disorders.
P7435 has demonstrated its lipid lowering potential in various preclinical studies by showing significant reduction in triglyceride levels, glucose and insulin levels,and decrease in food intake and body weight gain -factors which are associated with lipid abnormalities and metabolic disorders.
PEL has established the safety and tolerability of P7435 in a phase I trial recently completed in India. This extension trial in the US will further evaluate the safety and efficacy of P7435 in a larger population.
Dr Swati Piramal, vice chairperson, Piramal Enterprises, said, “The NCE Research division of PEL continues its ambitious diabetes/metabolic disorders programme to discover and develop NCEs to fight against diseases like diabetes and lipid disorders. With P7435 we are looking at addressing a serious need for effective and well-tolerated drugs that treat lipid disorders, which are commonly associated with diabetes and CVDs. Expansion of this trial will allow testing this NCE in a wider population,which is critical to the development of this drug and will provide therapeutic solutions not just to India but also to the rest of the world.”
The NCE Research division of Piramal Enterprises focuses on the discovery and development of innovative small molecule medicines to improve the lives of patients suffering from cancer, metabolic disorders and inflammatory conditions. The key elements of its strategy include capitalizing on Piramal’s strengths, in particular the India advantage, and leveraging external partnerships to achieve high levels of R&D productivity. Piramal’s state-of-the-art Research Centre in Mumbai has comprehensive capabilities spanning target identification all the way through clinical development. Its robust pipeline, including 8 compounds in clinical development, bears testimony to its innovative and rigorous drug discovery process.
PAPER
European Journal of Medicinal Chemistry (2012), 54, 324-342
http://www.sciencedirect.com/science/article/pii/S0223523412003133
PATENT
WO 2010023609
http://www.google.co.in/patents/WO2010023609A1?cl=en
/////////Piramal Enterprises, Mumbai, India, P-7435, P7435-DGAT1, P7435, P 7435, GDAT1 inhibitor
O=C(O)[C@@H](NC(=O)c1cc(no1)c2ccc(cc2)Nc3nc4ccc(F)cc4s3)C(C)C
Cas 1260006-20-9
Novartis
Target: CYP17/CYP11B2
Disease: Castration-resistant prostate cancer
MF C14H13ClN4O
MW: 288.0778
Elemental Analysis: C, 58.24; H, 4.54; Cl, 12.28; N, 19.40; O, 5.54
Steroid 17-alpha-hydroxylase inhibitors
CFG920 is a CYP17 inhibitor, is also an orally available inhibitor of the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17), with potential antiandrogen and antineoplastic activities. Upon oral administration, CYP17 inhibitor CFG920 inhibits the enzymatic activity of CYP17A1 in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells.
https://clinicaltrials.gov/ct2/show/NCT01647789
NCT01647789: A Study of Oral CFG920 in Patients With Castration Resistant Prostate Cancer2012
In August 2015, preclinical data were presented at the 250th ACS meeting in Boston, MA. In monkeys, treatment with CFG-920 (3 mg/kg, po) showed good bioavailability with F value of 93%, Tmax of 0.5 h, Cmax of 1382 nM.dn and AUC of 2364 nM.h, while CFG-920 (10 mg/kg, po) showed F value of 183%, Cmax of 1179 nM.dn and Tmax of 1.04 h
Bethany Halford on Twitter: “CFG920 – @Novartis CMOS for …
Novartis is developing CFG-920 (structure shown), an oral CYP17 inhibitor, for the potential treatment of metastatic castration-resistant prostate cancer. In March 2013, a phase I/II trial was initiated and at that time, the study was expected to complete in January 2015; in August 2015, clinical data were presented
2015 250th (August 19) Abs MEDI 341
Discovery of CFG920, a dual CYP17/CYP11B2 inhibitor, for the treatment of castration resistant prostate cancer
American Chemical Society National Meeting and Exposition
Christoph Gaul, Prakash Mistry, Henrik Moebitz, Mark Perrone, Bjoern Gruenenfelder, Nelson Guerreiro, Wolfgang Hackl, Peter Wessels, Estelle Berger, Mark Bock, Saumitra Sengupta, Venkateshwar Rao, Murali Ramachandra, Thomas Antony, Kishore Narayanan, Samiulla Dodheri, Aravind Basavaraju, Shekar Chelur
| Aurigene Discovery Technologies Limited, an independent subsidiary of Dr Reddy’s, CSN Murthy is chief executive officer |
WO 2010149755
Prostate cancer is the most commonly occurring cancer in men. Doctors often treat the metastatic stage of the disease by depriving the patient of sex hormones via chemical or surgical castration. But if it progresses far enough, the cancer can survive this therapy, transforming into the castration-resistant form. “Once the cancer becomes castration-resistant, the prognosis is poor,” said Novartis’s Christoph Gaul.
In recent years, CYP17, a bifunctional 17α-hydroxylase/17,20-lyase cytochrome P450 enzyme, has emerged as a target for treating castration-resistant prostate cancer. The enzyme catalyzes the biosynthesis of sex hormones, including testosterone, and blocking it can starve prostate cancer of the androgens it needs to thrive.
Johnson & Johnson’s CYP17 inhibitor, abiraterone acetate (Zytiga), a steroid that binds irreversibly to CYP17, was approved by the Food & Drug Administration in 2011. But Novartis scientists thought they could make a better CYP17 inhibitor, Gaul told C&EN. They teamed up with researchers at Aurigene, in Bangalore, India, and came up with their clinical candidate, CFG920.
Unlike abiraterone, CFG920 isn’t a steroid, and it inhibits CYP17 reversibly. It also reversibly inhibits another cytochrome P450 enzyme, CYP11B2, which is involved in the synthesis of the mineralocorticoids, hormones that regulate cardiac function.
Treating prostate cancer patients by lowering their androgen levels turns out to have negative cardiac side effects: Patients’ lipid metabolism is thrown off and their mineralocorticoid levels jump, leading to increases in blood pressure. Those changes can be stressful for the heart. “If prostate cancer patients don’t die because of the cancer, a lot of times they die because of cardiac disease,” Gaul said.
Because CFG920 also keeps mineralocorticoid levels in check, Novartis is hoping the drug candidate will ameliorate some of the cardiac side effects of inhibiting CYP17. The compound is currently in Phase I clinical trials.
PATENT
WO 2010149755
Example 58
Prύpιn”ation ofI'(2’ChIoroψ}ri(ibi-^’\l)’3’f4’metMψ}τUin’3’yl)-imiJazoliJin’2’θne (5HA)-
Using the same reaction conditions as in Example 14. 1-(4-methyl-pyridin-3-yl)- itnida/olidin-2-onc ().-.!.4b: 600 mg. 3.3898 mmol) uas reacted with 2-chloro-4-iodo- py.idine (974 mg.4.067 mmol). 1 , 4-dioxane (60 mL). copper iodide (65 mg, 0.3398 mmol), /r<w.v-1.2-diamino cycK)hexane (0.12 ml,, 1.0169 mmol) and potassium phosphate (2.15 g, 10.1694 mmol) to afford 810 mg of the product (83% yield).
1H NMR (C1DCI3. 300 Mi l/): 6 8.5-8.4 (m. 211). 8.3 (d. IH), 7.6-7.5 (m, 2H). 7.2 (S. 111). 4.1-3.9 (ni. 4H), 2.35 <s. 3H)
LCVIS puιϊt>: 90.8%. nι-7 – 289.1 (M M)
HPl C: 97.14%
REFERENCES
1: Gomez L, Kovac JR, Lamb DJ. CYP17A1 inhibitors in castration-resistant prostate cancer. Steroids. 2015 Mar;95:80-7. doi: 10.1016/j.steroids.2014.12.021. Epub 2015 Jan 3. Review. PubMed PMID: 25560485; PubMed Central PMCID: PMC4323677.
2: Yin L, Hu Q, Hartmann RW. Recent progress in pharmaceutical therapies for castration-resistant prostate cancer. Int J Mol Sci. 2013 Jul 4;14(7):13958-78. doi: 10.3390/ijms140713958. Review. PubMed PMID: 23880851; PubMed Central PMCID: PMC3742227.
///////CFG-920, CYP17 inhibitor (prostate cancer), Novartis, CFG 920, Novartis scientists, team up , researchers , Aurigene, Bangalore, India,
The generic APIs market is expected to continue to rise faster than the branded/innovative APIs, by 7.7%/year to reach $30.3 billion in 2016. Asia-Pacific is expected to show the fastest growth rates (10.8%/year). The 24 fastest growing markets will include 11 in Asia-Pacific, seven in Eastern Europe and CIS, four in Africa-Middle East and two in Latin America (Figure ).
Figure – Top growth markets for generic APIs to 2016
By 2016, China will account for 27.7% of the global generic API merchant market, while the US will have fallen to 23.8%; the mature markets as a whole will see their share fall from 41.8% in 2012 to 36.9%. India will be the third largest, with a 7.2% share.
………………………….
WO 2005009970
http://www.google.com/patents/WO2005009970A1?cl=en
preparation of Gatifloxacin hemihydrate from Ethyl-1- Cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylate through boron difluoride chelate. Ethyl-1-cyclopropyl- 6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylate is reacted with aqueous hydrofluoroboric acid followed by condensation with 2-methyl piperazine in polar organic solvent resulting in an intermediate l-Cyclopropyl-7- (3-methyl piperazin-1- yl). -6-fluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic acid boron difluoride chelate. This intermediate may be further hydrolyzed to yield Gatifloxacin. Gatifloxacin so obtained may needs purification to yield high purity product. However to obtain directly high purity Gatifloxacin it is desirable to isolate the intermediate by cooling to low temperatures . Treating with an alcohol or mixture of alcohols purifies this intermediate. The purified condensed chelate in aqueous ethanol on hydrolysis with triethylamine followed by crystallization in ethanol gives Gatifloxacin hemihydrate with high purity.
STAGE – I:
Ethyl l-cyclopropyl-6,7-difluoro-8-met oxy l-Cycloproρyl-6, 7-difluoro-8-methoxy -4-oxo-l, -dihydro-3-quinoline -4-oxo-l, 4-dihydro-3-quinoline carboxylate carboxylic acid boron difluoride chelate
STAGE – II :
l-Cycloprop l-7- ( 3-methylpiperazin-l-yl.
6-fluoro~8-methoxy-4-oxo-l , 4-dihydro-3- carboxylicacid borondifluoride chelate quinoline carboxylicacid borondifluoride chelate
STAGE -III :
l-Cyclopropyl-7- (3- ethylpiperaz.in-l-yl . GATIFLOXACIN
-6-fluoro-8-methoxy-4-oxo-l , 4-dihydro-3- quinoline carboxylicacid borondifluoride chelate
Example-I: Preparation of Gatifloxacin • with isolation of intermediate (boron difluoride chelate derivative)
Stage-1: Preparation of l-cyclopropyl-6, 7-di luoro-8-methoxy-4-oxo- 1, 4-dihydro-3-quinoline carboxylic acid boron difluoride chelate. Ethyl-l-cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, -dihydro-3- quinόline carboxylate (100g)is suspended in ,40%aq..hydrofluoroboric acid -(1000 ml). Temperature of • the reaction mass is raised and maintained at 95°C to 100°C for 5hrs followed by cooling to 30°C – 35°C. Water (400 ml) is added and maintained at 25°C – 30°C for 2hrs . Product is filtered, washed with water (500 ml) and dried at 40°C – 45°C to constant weight. Dry weight of the product: 101.6 g (Yield: 95.8 %)
Stage-2: Preparation of 1- Cyclopropyl-7- (3-methylpiperazin-l-yl) – 6-fluoro-8-methoxy-4-oxo-l, -dihydro-3-quinoline carboxylic acid boron difluoride chelate
100 g of Boron difluoride chelate derivative prepared as above in stage-1 is suspended in acetonitrile (800 ml) , to that 2-methyl piperazine (44.0 g, 1.5 mole equiv.) is added and mixed for 15 min to obtain a clear solution. The reaction mass is maintained at 30°C – 35°C for 12 hrs followed by cooling to -10°C to -5°C. The reaction mass is maintained at -10°C to -5°C for 1 hr. The product is filtered and dried at 45°C – 50°C to constant weight. Dry weight of the product: 116.0 g (Yield: 93.9 %) .
The condensed chelate (100 g) prepared as above is suspended in methanol (1500 ml), maintained at 40°C – 45°C for 30 min. The reaction mass is gradually cooled, maintained for 1 hr at -5°C to 0°C. The product is filtered, washed with methanol (50 ml) and dried at 45°C – 50°C to constant weight. Dry weight of the product: 80.0 g (Yield: 80.0 %)
Stage -3: Preparation of Gatifloxacin (Crude)
The pure condensed chelate (100.0 g) prepared as above in stage-2 is suspended in 20% aq. ethanol (1000 ml) , the temperature is raised and maintained at 75°C to 80°C for 2 hrs. The reaction mass is cooled, filtered to remove insolubles, distilled under vacuum to remove solvent. Fresh ethanol (200 ml) is added and solvent is removed under vacuum at temperature below 50°C. Ethanol (200 ml) is added to the residue and gradually cooled to -10°C to -5°C. The reaction mass is mixed at -10°C to -5°C for 1 hr and then filtered. The wet cake is washed with ethanol (25 ml) and dried at 45°C – 50°C to constant weight.
The dry weight of the Gatifloxacin is 83.3 g (Yield: 91.7 %)
Stage- 4: Purification of crude Gatifloxacin
Crude Gatifloxacin (100.0 g) prepared as above in stage-3 is suspended in methanol (4000 ml), the temperature is raised and maintained at 60°C to 65°C for 20 min. to get a clear solution. Activated carbon (5 g) is added, maintained for 30 min and the solution is filtered. The filtrate is concentrated to one third of its original volume under vacuum at temperature below 40°C. The reaction mass is gradually cooled and maintained at -10°C to -5°C for 2 hrs. The product is filtered, washed with methanol (50 ml) and dried at 45°C – 50°C to constant weight. The dry weight of the pure Gatifloxacin is 76.0 g (Yield: 76.0 %)
Example-II: Preparation of Gatifloxacin without isolation of intermediate (boron difluoride chelate derivative)
Stage-1: Preparation of l-cyclopropyl-6, 7-difluoro-8-methoxy-4- oxo-1, 4-dihydro-3-quinoline carboxylic acid boron difluoride chelate.
Ethyll-cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3- quinoline carboxylate (lOOg) is suspended in 40% aq. hydrofluoroboric acid (1000 ml) . Temperature of the reaction mass is raised and maintained at 95°C to 100°C for 5 hrs followed by cooling to 30°C – 35°C. 400 ml DM water is added, maintained at 25°C – 30°C for 2hrs . The product is filtered, washed with DM water (500 ml) and dried at 40°C – 45°C to constant weight. The dry wt is 102.5 g (Yield: 96.6 %)
Stage – 2: Preparation of Gatifloxacin (Crude)
The boron difluoride chelate derivative (100 g) prepared as above in stage-1 is suspended in acetonitrile (800 ml) , 2-methyl piperazine (44 g, 1.5 mole equiv.) is added and mixed for 15 min to obtain a clear solution. The reaction mass is maintained at 30°C – 35°C for 12 hrs. Removed the solvent by vacuum distillation. 20% Aq. ethanol (1000 ml) is added, raised the temperature and maintained at 75°C to 80°C for 2 hrs. The reaction mass is cooled, filtered to remove insolubles. The filtrate is distilled under vacuum to remove solvent completely. Fresh ethanol (250 ml) is added and distilled under vacuum at temperature below 50°C. Fresh Ethanol (250 ml) is added to the residue and gradually cooled to -10°C to -5°C. The reaction mass is maintained at -10°C to -5°C for 1 hr and filtered. The wet cake is washed with ethanol (30 ml) and dried at 45°C – 50°C to constant weight.
The dry weight of the Gatifloxacin is 73.5 g (Yield: 65.4 %)
Stage -3: Purification of crude Gatifloxacin
Crude Gatifloxacin (80.0 g) prepared as above in stage-2 is suspended in methanol (2000 ml) , the temperature is raised and maintained at 60°C to 65°C for 20 min. to get a clear solution. The reaction mixture is filtered. The filtrate is gradually cooled and maintained at -10°C to -5°C for 2 hrs. The product is filtered, washed with methanol (50 ml) and dried at 45°C – 50°C to constant weight.
The dry weight of the pure Gatifloxacin is 56.0 g (Yield: 70.0 %)
……………………….
WO 2005047260
http://www.google.co.in/patents/WO2005047260A1?cl=en
Gatifloxacin is the international common name of l-cyclopropyl-6-fluoro-l, 4-dihydro-8-methoxy- 1- (3-methyl-l-piperazinyl) -4-oxo-3-guinolin-carboxylic acid of formula (I) , with application in medicine and known for its antibiotic activity:
European patent application EP-A-230295 discloses a process for obtaining gatifloxacin that consists on the reaction of compound (II) with 2-
In this process the gatifloxacin is isolated in the form of a hemihydrate after a laborious process of column chromatography and recrystallisation in methanol, which contributes towards making the final yield lower than 20% by weight. Moreover, in said process an undesired by-product is formed, resulting from demethylation at position 8 of the ring. European patent application EP-A-241206 discloses a process for preparing gatifloxacin, whose final steps are as follows:
(III) H ft N Me H DMSO
Gatifloxacin (I)
(IV) This process uses the intermediate compound (III) , which has been prepared and isolated in a separate operation, while the intermediate compound (IV) is also isolated before proceeding to its conversion into gatifloxacin by treatment with ethanol in the presence of triethylamine. The overall yield from these three steps is lower than 40%. These disadvantages — a synthesis involving several steps, low yields, and the need to isolate the intermediate products — hinder the production of gatifloxacin on an industrial scale. There is therefore a need to provide a process for preparing gatifloxacin with a good chemical yield, without the need to isolate the intermediate compounds and that substantially avoids demethylation in position 8 of the ring. The processes termed in English “one pot” are characterised in that the synthesis is carried out in the same reaction vessel, without isolating the intermediate compounds, and by means of successive addition of the reacting compounds. The authors of the present invention have discovered a simplified process for preparing gatifloxacin which does not require isolation of the intermediate compounds .
Example 1: Preparing gatifloxacin from compound (II) 10 g (0.0339 moles, 1 equivalent) of compound
(II) is placed in a flask, 30 ml of acetonitryl (3 volumes) is added and this is heated to a temperature of 76-80° C.
Once reflux has been attained, and being the temperature maintained, 3.28 g (0.0203 moles, 0.6 equivalents) of hexamethyldisilazane (HMDS) is added with a compensated adding funnel. Once addition is completed, the reaction is maintained with stirring for 1 hour at a temperature of 76-80° C. Once this period has elapsed, the reaction mixture is cooled to a temperature ranging between 0 and 15° C, and 5.78 g (0.0407 moles, 1.2 equivalents) of boron trifluoride ethyletherate is added while keeping the temperature below 15° C. Once addition is completed, the temperature is allowed to rise to 15- 25° C and it is kept under these conditions for approximately 2 hours. The pH of the mixture is then adjusted to an approximate value of 9 with triethylamine (approximately 2 ml) . To the resulting suspension is added a solution of 10.19 g (0.1017 moles, 3 equivalents) of 2-methylpiperazine in 28 ml of acetonitryl, while maintaining the temperature between 15 and 25° C. The resulting amber solution is kept with stirring under these conditions for approximately 3 hours . Once the reaction has been completed, the solution is distilled at low pressure until a stirrable paste is obtained. At this point 50 ml of methanol is added, the resulting suspension is raised to a temperature of 63-67° C and is kept under these conditions for approximately 5 hours . Once the reaction has been completed, the mixture is cooled to a temperature of 25-35° C in a water bath, and then at a temperature of 0-5° C in a water/ice bath for a further 1 hour. The resulting precipitate is filtered, washed with cold methanol (2 x 10 ml) and dried at 40° C in a vacuum oven to constant weight. 10.70 g of crude gatifloxacin is obtained, having a water content of 2.95% by weight. The yield of the process is 81.8%.
The crude product is crystallised in methanol by dissolving 20 g of crude gatifloxacin in 1 1 of methanol (50 volumes) at a temperature of 63-67° C. Once all the product has been dissolved, the solution is left to cool to a temperature of 30-40° C, and then to a temperature of 0-5° C in a water/ice bath, maintaining it under these conditions for 1 hour. The resulting suspension is filtered and the solid retained is washed with 20 ml (1 volume) of cold methanol. The solid obtained is dried at 40° C in a vacuum oven to provide 18.65 g of gatifloxacin with a water content of 2.36% by weight.
The overall yield from the compound (II) is 77.7%, with a purity exceeding 99.8% as determined by HPLC chromatography. The content of by-product resulting from demethylation in position 8 of the ring is lower than 0.1% as determined by HPLC chromatography.
 |
|
| Systematic (IUPAC) name | |
|---|---|
| 1-cyclopropyl-6-fluoro- 8-methoxy-7-(3-methylpiperazin-1-yl)- 4-oxo-quinoline-3-carboxylic acid | |
| Clinical data | |
| Trade names | Zymar |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a605012 |
|
|
| Oral (discontinued), Intravenous(discontinued) ophthalmic |
|
| Pharmacokinetic data | |
| Protein binding | 20% |
| Half-life | 7 to 14 hours |
| Identifiers | |
112811-59-3  |
|
| J01MA16 S01AE06 | |
| PubChem | CID: 5379 |
| DrugBank | DB01044 |
| ChemSpider | 5186 |
| UNII | 81485Y3A9A |
| KEGG | D08011 |
| ChEBI | CHEBI:5280 |
| ChEMBL | CHEMBL31 |
| NIAID ChemDB | 044913 |
| Chemical data | |
| Formula | C19H22FN3O4 |
| 375.394 g/mol | |
PAPER
An improved process to obtain gatifloxacin (1) through use of boron chelate intermediates has been developed. The methodology involves an initial activation step which accelerates the formation of the first chelate under low-temperature conditions and prevents demethylation of the starting material. To increase the overall yield and to avoid the isolation and manipulation of the resulting intermediates, the process has been designed to be carried out in one pot. As a result, we present here an easy, scaleable and substantially impurity-free process to obtain gatifloxacin (1) in high yield.
DSC analysis showed two endothermic peaks at 166.2 °C (T onset = 164.3 °C) and 190.0 °C (T onset = 188.2 °C) and an exothermic one at 168.1 °C. The shape of this DSC curve is characteristic of a monotropic transition between crystalline forms
Although there are several hydrates described for gatifloxacin such as, among others, the hemimydrate, sesquihydrate, and pentahydrate(Raghavan, K. S.; Ranadive, S. A.;Gougoutas, J. Z.; Dimarco, J. D.; Parker, W. L.; Dovich, M.; Neuman, A.Gatifloxacin pentahydrate. WO 2002/22126 A1, 2002) , the Gatifloxacin obtained by the present procedure does not seem to form a stoichometric hydrate, but instead it retains moisture.
Thus, the product is usually obtained with a Karl-Fischer value below 1% after drying, but it can absorb moisture until a final content of about 3%. This water content can vary between 2.0% and 3.5%, depending on the relative humidity of the environment. DSC analysis revealed a broad endothermic signal with minimum at 76 °C, while TGA analysis showed that the product loses all the water below 80 °C.
No loss of weight is registered when the product melts, and the weight is constant until the decomposition of the material at about 200 °C. On the basis of these results, it can be said that the water content of the gatifloxacin obtained by the present process is retained moisture instead of water belonging to the lattice. The shape of the derivative of the weight curve at the beginning of the analysis shows that the sample has already lost part of the moisture when the register starts. This is probably due to the sample starting to lose weight when makes contact with the dry atmosphere of the TGA oven that could explain the different values obtained for water content of the analyzed sample by TGA (1.90%) and Karl-Fischer (2.64%) methods.
A Canadian study published in the New England Journal of Medicine in March 2006 claims Tequin can have significant side effectsincluding dysglycemia.[2] An editorial by Dr. Jerry Gurwitz in the same issue called for the Food and Drug Administration (FDA) to consider giving Tequin a black box warning.[3] This editorial followed distribution of a letter dated February 15 by Bristol-Myers Squibb to health care providers indicating action taken with the FDA to strengthen warnings for the medication.[4] Subsequently it was reported on May 1, 2006 that Bristol-Myers Squibb would stop manufacture of Tequin, end sales of the drug after existing stockpiles were exhausted, and return all rights to Kyorin.[5]
Union Health and Family Welfare Ministry of India on 18 March 2011 banned the manufacture, sale and distribution of Gatifloxacin as it caused certain adverse side effects[6]
Gatifloxacin is currently available only in the US and Canada as an ophthalmic solution.
In China it is sold in tablet as well as in eye drop formulations.
Ophthalmic anti-infectives are generally well tolerated. The concentration of the drug observed following oral administration of 400 mg gatifloxacin systemically is approximately 800 times higher than that of the 0.5% Gatifloxacin eye drop. Given as an eye drop, Gatifloxacin Ophthalmic Solution 0.3% & 0.5% cause very low systemic exposures. Therefore, the systemic exposures resulting from the gatifloxacin ophthalmic solution are not likely to pose any risk for systemic toxicities.
 |
|
Title: Gatifloxacin
CAS Registry Number: 112811-59-3
CAS Name: 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid
Trademarks: Tequin (BMS); Zymar (Allergan)
Molecular Formula: C19H22FN3O4
Molecular Weight: 375.39
Percent Composition: C 60.79%, H 5.91%, F 5.06%, N 11.19%, O 17.05%
Literature References: Fluorinated quinolone antibacterial. Prepn: K. Masuzawa et al., EP 230295; eidem, US 4980470 (1987, 1990 both to Kyorin); J. P. Sanchez et al., J. Med. Chem. 38, 4478 (1995); of the sesquihydrate: T. Matsumoto et al., US5880283 (1999 to Kyorin). In vitro antibacterial activity: A. Bauernfeind, J. Antimicrob. Chemother. 40, 639 (1997); H. Fukuda et al., Antimicrob. Agents Chemother. 42, 1917 (1998). Clinical pharmacokinetics: M. Nakashima et al., ibid. 39, 2635 (1995). Clinical study in urinary tract infection: H. Nito, 10th Mediterranean Congr. Chemother. 1996, 327; in respiratory tract infection: S. Sethi, Expert Opin. Pharmacother. 4, 1847 (2003).
Properties: Pale yellow prisms from methanol as hemihydrate, mp 162°.
Melting point: mp 162°
Derivative Type: Sesquihydrate
CAS Registry Number: 180200-66-2
Manufacturers’ Codes: AM-1155
Molecular Formula: C19H22FN3O4.1½H2O
Molecular Weight: 384.40
Percent Composition: C 59.37%, H 6.03%, F 4.94%, N 10.93%, O 18.73%
Therap-Cat: Antibacterial.
Keywords: Antibacterial (Synthetic); Quinolones and Analogs
|
| EP0610958A2 * | 20 Jul 1989 | 17 Aug 1994 | Ube Industries, Ltd. | Intermediates in the preparation of 4-oxoquinoline-3-carboxylic acid derivatives |
| ES2077490A1 * | Title not available |
| Citing Patent | Filing date | Publication date | Applicant | Title |
|---|---|---|---|---|
| WO2008126384A1 | 31 Mar 2008 | 23 Oct 2008 | Daiichi Sankyo Co Ltd | Method for producing quinolone carboxylic acid derivative |
| CN101659654B | 28 Aug 2008 | 6 Nov 2013 | 四川科伦药物研究有限公司 | 2-Methylpiperazine fluoroquinolone compound and preparation method and application thereof |
| CN102351843A * | 18 Aug 2011 | 15 Feb 2012 | 张家口市格瑞高新技术有限公司 | Synthesis method of 2-methyl piperazine lomefloxacin |
| EP1832587A1 * | 2 Mar 2007 | 12 Sep 2007 | Quimica Sintetica, S.A. | Method for preparing moxifloxacin and moxifloxacin hydrochloride |
| US7365201 | 2 Mar 2006 | 29 Apr 2008 | Apotex Pharmachem Inc. | Process for the preparation of the boron difluoride chelate of quinolone-3-carboxylic acid |
| US7875722 | 30 Sep 2009 | 25 Jan 2011 | Daiichi Sankyo Company, Limited | Method for producing quinolone carboxylic acid derivative |
| EP0464823A1 * | Jul 4, 1991 | Jan 8, 1992 | Kyorin Pharmaceutical Co., Ltd. | (6,7-Substituted-8-alkoxy-1-cyclopropyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid-O3,O4)bis(acyloxy-O)borates and the salts thereof, and methods for their manufacture |
| US4997943 * | Mar 31, 1987 | Mar 5, 1991 | Sankyo Company Limited | Quinoline-3-carboxylic acid derivatives |
| Citing Patent | Filing date | Publication date | Applicant | Title |
|---|---|---|---|---|
| CN101659654B | Aug 28, 2008 | Nov 6, 2013 | 四川科伦药物研究有限公司 | 2-Methylpiperazine fluoroquinolone compound and preparation method and application thereof |
| CN102351843A * | Aug 18, 2011 | Feb 15, 2012 | 张家口市格瑞高新技术有限公司 | Synthesis method of 2-methyl piperazine lomefloxacin |
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Amritsar, punjab, India
Amritsar is one of the largest cities of the Punjab state in India. The city origin lies in the village of Tung, and was named after the lake founded by the fourth Sikh …
GOLDEN TEMPLE
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Tandoori chicken at Surjit Food Plaza. amritsar
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The Jallianwalla Bagh in 1919, months after the massacre
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The holy water
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Laboratory-scale spray dryer.
A=Solution or suspension to be dried in, B=Atomization gas in, 1= Drying gas in, 2=Heating of drying gas, 3=Spraying of solution or suspension, 4=Drying chamber, 5=Part between drying chamber and cyclone, 6=Cyclone, 7=Drying gas is taken away, 8=Collection vessel of product, arrows mean that this is co-current lab-spraydryer
Spray drying is a method of producing a dry powder from a liquid or slurry by rapidly drying with a hot gas. This is the preferred method of drying of many thermally-sensitive materials such as foods and pharmaceuticals. A consistent particle size distribution is a reason for spray drying some industrial products such as catalysts. Air is the heated drying medium; however, if the liquid is a flammable solvent such as ethanol or the product is oxygen-sensitive then nitrogen is used.[1]
All spray dryers use some type of atomizer or spray nozzle to disperse the liquid or slurry into a controlled drop size spray. The most common of these are rotary disks and single-fluid high pressure swirl nozzles. Atomizer wheels are known to provide broader particle size distribution, but both methods allow for consistent distribution of particle size.[2] Alternatively, for some applications two-fluid or ultrasonic nozzles are used. Depending on the process needs, drop sizes from 10 to 500 µm can be achieved with the appropriate choices. The most common applications are in the 100 to 200 µm diameter range. The dry powder is often free-flowing.[3]
The most common spray dryers are called single effect as there is only one drying air on the top of the drying chamber (see n°4 on the scheme). In most cases the air is blown in co-current of the sprayed liquid. The powders obtained with such type of dryers are fine with a lot of dusts and a poor flowability. In order to reduce the dusts and increase the flowability of the powders, there is since over 20 years a new generation of spray dryers called multiple effect spray dryers. Instead of drying the liquid in one stage, the drying is done through two steps: one at the top (as per single effect) and one for an integrated static bed at the bottom of the chamber. The integration of this fluidized bed allows, by fluidizing the powder inside a humid atmosphere, to agglomerate the fine particles and to obtain granules having commonly a medium particle size within a range of 100 to 300 µm. Because of this large particle size, these powders are free-flowing.
The fine powders generated by the first stage drying can be recycled in continuous flow either at the top of the chamber (around the sprayed liquid) or at the bottom inside the integrated fluidized bed. The drying of the powder can be finalized on an external vibrating fluidized bed.
The hot drying gas can be passed as a co-current or counter-current flow to the atomiser direction. The co-current flow enables the particles to have a lower residence time within the system and the particle separator (typically a cyclone device) operates more efficiently. The counter-current flow method enables a greater residence time of the particles in the chamber and usually is paired with a fluidized bed system.
Alternatives to spray dryers are:[4]
Spray drying nozzles.
Schematic illustration of spray drying process.
A spray dryer takes a liquid stream and separates the solute or suspension as a solid and the solvent into a vapor. The solid is usually collected in a drum or cyclone. The liquid input stream is sprayed through a nozzle into a hot vapor stream and vaporised. Solids form as moisture quickly leaves the droplets. A nozzle is usually used to make the droplets as small as possible, maximising heat transfer and the rate of water vaporisation. Droplet sizes can range from 20 to 180 μm depending on the nozzle.[3] There are two main types of nozzles: high pressure single fluid nozzle (50 to 300 bars) and two-fluid nozzles: one fluid is the liquid to dry and the second is compressed gas (generally air at 1 to 7 bars).
Spray dryers can dry a product very quickly compared to other methods of drying. They also turn a solution, or slurry into a dried powder in a single step, which can be advantageous for profit maximization and process simplification.
The spray drying process is older than might commonly be imagined. Earliest descriptions date from 1860 with the first patented design recorded in 1872. The basic idea of spray drying is the production of highly dispersed powders from a fluid feed by evaporating the solvent. This is achieved by mixing a heated gas with an atomized (sprayed) fluid of high surface-to-mass ratio droplets, ideally of equal size, within a vessel (drying chamber), causing the solvent to evaporate uniformly and quickly through direct contact.
Spray drying can be used in a wide range of applications where the production of a free-flowing powder is required. This method of dehydration has become the most successful one in the following areas:
Almost all other methods of drying, including use of ovens, freeze dryers or rotary evaporators, produce a mass of material requiring further processing (e.g. grinding and filtering) therefore, producing particles of irregular size and shape. Spray drying on the other hand, offers a very flexible control over powder particle properties such as density, size, flow characteristics and moisture content.
The challenges facing both designers and users are to increase production, improve powder quality and reduce costs. This requires an understanding of the process and a robust control implementation.
Spray drying consists of the following phases:
1. Pressure nozzle atomization: Spray created by forcing the fluid through an orifice. This is an energy efficient method which also offers the narrowest particle size distribution.
2. Two-fluid nozzle atomization: Spray created by mixing the feed with a compressed gas. Least energy efficient method. Useful for making extremely fine particles.
3. Centrifugal atomization: Spray created by passing the feed through or across a rotating disk. Most resistant to wear and can generally be run for longer periods of time.
A control system must therefore provide flexibility in the way in which accurate and repeatable control of the spray drying is achieved and will include the following features:
Spray drying often is used as an encapsulation technique by the food and other industries. A substance to be encapsulated (the load) and an amphipathic carrier (usually some sort of modified starch) are homogenized as a suspension in water (the slurry). The slurry is then fed into a spray drier, usually a tower heated to temperatures well over the boiling point of water.
As the slurry enters the tower, it is atomized. Partly because of the high surface tension of water and partly because of thehydrophobic/hydrophilic interactions between the amphipathic carrier, the water, and the load, the atomized slurry forms micelles. The small size of the drops (averaging 100 micrometers in diameter) results in a relatively large surface area which dries quickly. As the water dries, the carrier forms a hardened shell around the load.[5]
Load loss is usually a function of molecular weight. That is, lighter molecules tend to boil off in larger quantities at the processing temperatures. Loss is minimized industrially by spraying into taller towers. A larger volume of air has a lower average humidity as the process proceeds. By the osmosis principle, water will be encouraged by its difference in fugacities in the vapor and liquid phases to leave the micelles and enter the air. Therefore, the same percentage of water can be dried out of the particles at lower temperatures if larger towers are used. Alternatively, the slurry can be sprayed into a partial vacuum. Since the boiling point of a solvent is the temperature at which the vapor pressure of the solvent is equal to the ambient pressure, reducing pressure in the tower has the effect of lowering the boiling point of the solvent.
The application of the spray drying encapsulation technique is to prepare “dehydrated” powders of substances which do not have any water to dehydrate. For example, instant drink mixes are spray dries of the various chemicals which make up the beverage. The technique was once used to remove water from food products; for instance, in the preparation of dehydrated milk. Because the milk was not being encapsulated and because spray drying causes thermal degradation, milk dehydration and similar processes have been replaced by other dehydration techniques. Skim milk powders are still widely produced using spray drying technology around the world, typically at high solids concentration for maximum drying efficiency. Thermal degradation of products can be overcome by using lower operating temperatures and larger chamber sizes for increased residence times.[6]
Recent research is now suggesting that the use of spray-drying techniques may be an alternative method for crystallization of amorphous powders during the drying process since the temperature effects on the amorphous powders may be significant depending on drying residence times.[7][8]
Food: milk powder, coffee, tea, eggs, cereal, spices, flavorings, starch and starch derivatives, vitamins, enzymes, stevia, colourings, etc.
Pharmaceutical: antibiotics, medical ingredients, additives
Industrial: paint pigments, ceramic materials, catalyst supports, microalgae
The nano spray dryer offers new possibilities in the field of spray drying. It allows to produce particles in the range of 300 nm to 5 μm with a narrow size distribution. High yields are produced up to 90% and the minimal sample amount is 1 mL.
Pharmaceutical Spray drying is a very fast method of drying due to the very large surface area created by the atomization of the liquid feed. As a consequence, high heat transfer coefficients are generated and the fast stabilisation of the feed at moderate temperatures makes this method very attractive for heat sensitive materials.
Spray drying provides unprecedented particle control and allows previously unattainable delivery methods and molecular characteristics. These advantages allow exploration into employing previously unattainable delivery methods and molecular characteristics.
Five things you might not know about spray drying
The spray drying process
Spray drying is a very fast method of drying due to the very large surface area created by the atomization of the liquid feed and high heat transfer coefficients generated. The short drying time, and consequently fast stabilisation of feed material at moderate temperatures, means spray drying is also suitable for heat-sensitive materials.
As a technique, spray drying consists of four basic stages:
Ahmednagar is a medieval city. Numerous Mughal-era buildings dot the environs
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Patent EP0922715B1 – Stimuli-responsive polymer utilizing keto …
Carbonyl compounds (aldehydes, ketones, carboxylic esters, carboxylic amides) react aselectrophiles at the sp2 hybridized carbon atoms and as nucleophiles if they contain an H-atom in the α-position relative to their C=O or C=N bonds. This is because this H is acidic and it can be removed by a base leaving behind an electron pair for nucleophilic attacks.
For most compounds in organic chemistry all the molecules have the same structure – even if this structure cannot satisfactory represented by a Lewis formula – but for many compounds there is a mixture of two or more structurally distinct compounds that are in rapid equilibrium. This phenomenon is called tautomerism.
Tautomerism is the phenomenon that occurs in any reaction that simply involves the intramolecular transfer of a proton. An equilibrium is established between the two tautomers (structurally distinct compounds) and there is a rapid shift back and forth between the distinct compounds.
A very common form of tautomerism is that between a carbonyl compound containing an α–hydrogen and its enol form (Fig. I.1).
An enol is exactly what the name implies: an ene-ol. It has a C=C double bond (diene) and an OH group (alcohol) joined directly to it.
Notice that in the above reaction as in any keto-enol reaction there is no change in pH since a proton is lost from carbon and gained on oxygen. The reaction is known as enolization as it is the conversion of a carbonyl compound into its enol.
Notice also that in the above reaction the product is almost the same as the starting material since the only change is the transfer of one proton and the shift of the double bond.
In simple cases (R2 = H, alkyl, OR, etc.) the equilibrium of the keto-enol reaction lies well to the left (keto structure) (Table I.1). The reason can be seen by examining the bond energies in Table I.2.
|
Compound |
Enol Content, % |
|
Acetone |
6 * 10-7 |
|
PhCOCH3 |
1.1 * 10-6 |
|
CH3CHO |
6 * 10-5 |
|
Cyclohexanone |
4 * 10-5 |
|
Ph2CHCHO |
9.1 |
|
PhCOCH2COCH3 |
89.2 |
Table I.1: The enol content of some carbonyl compounds
If keto-enol reactions are common for aldehydes and ketones why don’t simple aldehydes and ketones exist as enols?
IR and NMR Spectra of carbonyl compounds show no signs of enols. The equilibrium lies well over towards the keto form (the equilibrium constant k for cyclohexanone is about 10-5).
|
|
Bond (Energy, kJ/mol) |
Sum ( kJ/mol) |
||
|
keto form |
C-H (413) |
C-C (350) |
C=O (740) |
1503 |
|
enol form |
C=C (620) |
C-O (367) |
O-H (462) |
1449 |
Table I.2: Bond energies in the keto and in the enol form. The keto form is thermodynamically more stable than the enol form by approximately 50 kJ/mol
The approximate sum of the bond energies in the keto form is 1503 kJ/mol while in the enol form 1449. Therefore, the keto form is thermodynamically more stable than the enol form by approximately 50 kJ/mol.
In most cases, enol forms cannot be isolated since they are less stable and are formed in minute quantities. However, there are some exceptions and in certain cases a larger amount of the enol form is present and it can be even the predominant species:
Is there experimental evidence that keto-enol reactions are common for aldehydes and ketones?
If the NMR spectrum of a simple carbonyl compound in D2O is obtained – such as pinacolone’s (CH3)3CCOCH3 – the signal for protons next to the carbonyl group very slowly disappears. The isolated compound’s mass spectrum (after the above mentioned reaction with D2O is over) shows that those hydrogen atoms have been replaced by deuterium atoms. There is a peak at (M+1)+ or (M+2)+ or (M+3)+ instead of M+. The reaction is shown in Fig. I.3:
What mechanism can be proposed for the above reaction?
Enolization is a slow process in neutral solution, even in D2O, and is catalyzed by acid or base in order to happen.
In the acid-catalyzed reaction the molecule is first protonated on oxygen and then loses the C-H proton in a second step (Fig. I.4). When the enol form reverts to the keto – since this is an equilibrium process – it picks up a deuteron instead of a proton since the solution is D2O.
In the base-catalyzed reaction the C-H proton is removed first by the base (for example hydroxide ion OH–, OD– in our case) and the proton (or D+ in our case) added to the oxygen atom in a second step (Fig. I.5).
Notice that the enolization reactions in Fig. I.4 and Fig. I.5 are catalytic. In the acid-catalyzed mechanism the D+ (or H+ if water is the solvent) is regenerated at the end (catalyst). In the base-catalyzed mechanism OD– (or OH– if water is the solvent) is regenerated at the end (catalyst).
The enolate ion generated from the enol (Fig. I.6) in the base-catalyzed mechanism is nucleophilic due to:
An enolate ion is an ion with a negative charge on oxygen with adjacent C-C double bond.
Enolates are reactive nucleophiles. Although the major enolate Lewis contributor shows concentration of electron density on the electronegative oxygen when it reacts as a nucleophile, it behaves like the electron density is concentrated on the α-carbon next to carbonyl group.
Enolates react with alkyl halides, aldehydes/ketones and esters and these reactions are shown in the post entitled “The chemistry of enolate ions – Enolate ion reactions”.
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http://www.slideshare.net/chemsant/nmr-dynamic
http://article.sapub.org/10.5923.j.ajoc.20140401.01.html
2-fluoro-3-hydroxycyclopent-2-enone and 2-fluoro- 1,3-cyclopentanedione (1c): This compound was obtained as a 52:48 mixture of keto-enol and diketo tautomers in 50% yield as a yellow-brown solid, mp 70-72°C. NMR:1H: δ 2.36 (t, 3JH-H = 16.2 Hz, 2H), 2.85 (m, 2H), 5.91 (d, 2JH-F = 47.7 Hz, 1H). 13C: δ31.1, 90.8 (d, 1JC-F = 251.3 Hz), 122.3 (d, 1JC-F = 233.9 Hz), 210.1 (d, 2JC-F = 31.0 Hz). 19F: keto-enol: δ-161.4 (s, 1F); diketo: δ-195.5 (d, 2JF-H = 47.7 Hz, 1F). Analysis calcd for C5H5FO2: C, 51.73, H, 4.34. Found: C, 51.48, H, 4.31.
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Surat, previously known as Suryapur, is a city in the Indian state of Gujarat. It is the administrative capital of the Surat district. The city is located 306 km south of …
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ISKCON
Surat-European tombs
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Kathiyavadi food, Garden Restaurant, Restaurant in surat, Restaurant, Restaurant Services, Food
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Amalner, India is a city and a municipal council in Jalgaon district in the state of Maharashtra, India, situated on the bank of the Bori River. Amalner is the …
10000 devout Hindus were present for the Hindu Dharmajagruti Sabha at Amalner, Maharashtra
end of amalner…………
Daulatabad also known as Devagiri is a town which includes the Devagiri-Daulatabad fort It carries the distinction of remaining undefeated in battle.
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WEBSITE http://www.scientificupdate.co.uk/
TRAINING COURSE 2-3 DEC 2014
Process Development for Low Cost Manufacturing
When:02.12.2014 – 03.12.2014
Tutors:
Where: National Chemical Laboratory – Pune, India
Brochure:View Brochure
Register http://scientificupdate.co.uk/training/scheduled-training-courses.html
Chemical process research and development is recognised as a key function during the commercialisation of a new product particularly in the generic and contract manufacturing arms of the chemical, agrochemical and pharmaceutical industries.
The synthesis and individual processes must be economic, safe and must generate product that meets the necessary quality requirements.
This 2-day course presented by highly experienced process chemists will concentrate on the development and optimisation of efficient processes to target molecules with an emphasis on raw material cost, solvent choice, yield improvement, process efficiency and work up, and waste minimisation.
Process robustness testing and reaction optimisation via stastical methods will also be covered.
A discussion of patent issues and areas where engineering and technology can help reduce operating costs.
The use of engineering and technology solutions to reduce costs will be discussed and throughout the course the emphasis will be on minimising costs and maximising returns.
Conference 4-5 DEC 2014
TITLE . Organic Process Research & Development – India
Subtitle:The 32nd International Conference and Exhibition
When:04.12.2014 – 05.12.2014
Where:National Chemical Laboratory – Pune, India
Brochure:View Brochure
Register..http://scientificupdate.co.uk/conferences/conferences-and-workshops.html
for
Benefits
The efficient conversion of a chemical process into a process for manufacture on tonnage scale has always been of importance in the chemical and pharmaceutical industries. However, in the current economic and regulatory climate, it has become increasingly vital and challenging to do so efficiently. Indeed, it has never been so important to keep up to date with the latest developments in this dynamic field.
At this Organic Process Research & Development Conference, you will hear detailed presentations and case studies from top international chemists. The hand-picked programme of speakers has been put together specifically for an industrial audience. They will discuss the latest issues relating to synthetic route design, development and optimisation in the pharmaceutical, fine chemical and allied fields. Unlike other conferences, practically all our speakers are experts from industry, which means the ideas and information you take home will be directly applicable to your own work.
The smaller numbers at our conferences create a more intimate atmosphere. You will enjoy plenty of opportunities to meet and network with speakers and fellow attendees during the reception, sit-down lunches and extended coffee breaks in a relaxed and informal environment. Together, you can explore the different strategies and tactics evolving to meet today’s challenges.
This is held in Pune, close proximity to Mumbai city, very convenient to stay and travel to either in Pune or Mumbai. I feel this should be an opportunity to be grabbed before the conference is full and having no room
Hurry up rush
References
1 http://newdrugapprovals.org/scientificupdate-uk-on-a-roll/
2 http://scientificupdate.co.uk/conferences/conferences-and-workshops.html
3 http://en.wikipedia.org/wiki/Pune
PROFILES
Dr Will Watson gained his PhD in Organic Chemistry from the University of Leeds in 1980. He joined the BP Research Centre at Sunbury-on-Thames and spent five and a half years working as a research chemist on a variety of topics including catalytic dewaxing, residue upgrading, synthesis of novel oxygenates for use as gasoline supplements, surfactants for use as gasoline detergent additives and non-linear optical compounds.
In 1986 he joined Lancaster Synthesis and during the next 7 years he was responsible for laboratory scale production and process research and development to support Lancaster’s catalogue, semi-bulk and custom synthesis businesses.
In 1993 he was appointed to the position of Technical Director, responsible for all Production (Laboratory and Pilot Plant scale), Process Research and Development, Engineering and Quality Control. He helped set up and run the Lancaster Laboratories near Chennai, India and had technical responsibility for the former PCR laboratories at Gainesville, Florida.
He joined Scientific Update as Technical Director in May 2000. He has revised and rewritten the ‘Chemical Development and Scale Up in the Fine Chemical & Pharmaceutical Industries’ course and gives this course regularly around the world. He has been instrumental in setting up and developing new courses such as ‘Interfacing Chemistry with Patents’ and ‘Making and Using Fluoroorganic Molecules’.
He is also involved in an advisory capacity in setting up conferences and in the running of the events. He is active in the consultancy side of the business and sits on the Scientific Advisory Boards of various companies.
………………………………………………………………………………………………….
Dr John Knight gained a first class honours degree in chemistry at the University of Southampton, UK. John remained at Southampton to study for his PhD in synthetic methodology utilizing radical cyclisation and dipolar cyloaddition chemistry.
After gaining his PhD, John moved to Columbia University, New York, USA where he worked as a NATO Postdoctoral Fellow with Professor Gilbert Stork. John returned to the UK in 1987 joining Glaxo Group Research (now GSK) as a medicinal chemist, where he remained for 4 years before moving to the process research and development department at Glaxo, where he remained for a further 3½ years.
During his time at Glaxo, John worked on a number of projects and gained considerable plant experience (pilot and manufacturing). In 1994 John moved to Oxford Asymmetry (later changing its name to Evotec and most recently to Aptuit) when it had just 25 staff. John’s major role when first at Oxford Asymmetry was to work with a consultant project manager to design, build and commission a small pilot plant, whilst in parallel developing the chemistry PRD effort at Oxford Asymmetry.
The plant was fully operational within 18 months, operating to a 24h/7d shift pattern. John continued to run the pilot plant for a further 3 years, during which time he had considerable input into the design of a second plant, which was completed and commissioned in 2000. After an 18-month period at a small pharmaceutical company, John returned to Oxford in 2000 (by now called Evotec) to head the PRD department. John remained in this position for 6.5 years, during which time he assisted in its expansion, established a team to perform polymorph and salt screening studies and established and maintained high standards of development expertise across the department.
John has managed the chemical development and transfer of numerous NCE’s into the plant for clients and been involved in process validations. He joined Scientific Update in January 2008 as Scientific Director.
Pune images
From top:1 Fergusson College, 2 Mahatma Gandhi Road, Shaniwarwada 3 the HSBC Global Technology India Headquarters, and the 4National War Memorial Southern Command
NCL PUNE
The National Chemical Laboratory is located in the state of Maharashtra in India. Maharashtra state is the largest contributor to India’s GDP. The National Chemical Laboratory is located in Pune city, and is the cultural capital of Maharashtra. Pune city is second only to Mumbai (the business capital of India) in size and industrial strength. Pune points of interest include: The tourist places in Pune include: Lal Deval Synagogue, Bund Garden, Osho Ashram, Shindyanchi Chhatri and Pataleshwar Cave Temple.
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KEYWORDS
JOHN KNIGHT, WILL WATSON, SCIENTIFIC UPDATE, PROCESS, COURSE, CONFERENCE, INDIA, PUNE, PROCESS DEVELOPMENT, LOW COST, MANUFACTURING, SCALEUP
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tandoori chicken
