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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

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 30 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, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, 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 Open superstar 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 30 year tenure till date Dec 2017, Around 35 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, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , 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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New Patent, Tedizolid phosphate, Suzhou MiracPharma Technology Co Ltd, Zheren Pharmaceutical Nanjing Co Ltd, WO 2016058467


Tedizolid phosphate

Suzhou MiracPharma Technology Co Ltd; Zheren Pharmaceutical Nanjing Co Ltd

WO-2016058467   click for patent

SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD [CN/CN]; Room 1305, Building 1 Lianfeng Commercial Plaza, Industrial District Suzhou, Jiangsu 215000 (CN).
ZHEREN PHARMACEUTICAL NANJING CO., LTD [CN/CN]; Qiaolin Industry Park 32-71, Pukou District Nanjing, Jiangsu 211806 (CN)

Disclosed is a method for preparing tedizolid phosphate (I), and the preparation step thereof comprises producing the tedizolid phosphate (I) by means of a coupling reaction of a compound of formula II and a compound of formula III. The preparation method uses easily available raw materials and a simple process, is economical and environmentally friendly, and is suitable for industrial production.

front page image

Process for preparing tedizolid phosphate (TD-P), useful for treating bacterial infection. The present filing represents the first PCT and first filing to be seen from Suzhou Miracpharma and Zheren Pharmaceutical, respectively, that focuses on tedizolid; however this case was first seen as a Chinese national filing (assigned to Suzhou Miracpharma), published in February 2015. The drug was developed and launched by Dong-A ST and licensees Cubist Pharmaceuticals and Bayer, for treating acute bacterial skin and skin structure infections.

Tedizolid phosphate by Charpy Manchester (Cubist) pharmaceutical companies to develop a oxazolidinone antibiotics. Tedizolid phosphate in June 2014 to obtain FDA approval in the United States, the trade name Sivextro. The drug was first approved by the FDA in the second generation oxazolidinone antibiotics, and linezolid compared to the previous generation, Sivextro some bacteria in vitro inhibitory activity 2-8 times higher security to a certain extent also improved. Because compound Tedizolid not have standard Chinese translation, so the applicant where it is transliterated as “Thai to acetazolamide.”
Thailand phosphate to acetazolamide (Tedizolid phosphate) Chemical name: {(5R) -3- [3- fluoro-4- [6- (2-methyl–2H- tetrazol -5-yl) pyridine-3 yl] phenyl] -2-oxazolone -5-yl} methanol phosphate (I), having the formula:
Preparation of phosphate Thailand to acetazolamide has been reported, PCT Patent No. WO2005058886, No. WO2010042887 and “European Journal of Medicinal Chemistry” 2011 on 1027 – 1039 Section 46 were reported to temozolomide and phosphate Thai analog synthesis and related intermediates. Comparative summary of these methods, which are synthetic route from Intermediate A and Intermediate B (or intermediate B ‘) by an aryl coupling reaction to achieve.
Wherein 2- (2-methyl-tetrazol-5-yl) -5-bromopyridine (Intermediate A) is generated by a tetrazolium derivative azide reaction of 2-cyano-5-bromopyridine, and then the use of methyl iodide or dimethyl sulfate, etc. methylating reagent for tetrazole ring methylation reaction, to give 2- (2-methyl-tetrazol-5-yl) -5-bromopyridine (intermediate A ) and (1-methyl-tetrazol-5-yl) -5-bromo pyridine (by-product) in a mixture of 2, by column chromatography or recrystallization to give the intermediate separator A.
Intermediate B or B ‘by R-3- (3- fluoro-4-iodo-phenyl) -2-oxo-5-oxazolidinyl methanol formed organoboron reagent or an organotin reagent, the reagent is Stille or Suzuki coupling reactions, realize intermediate a coupling.
This shows that the existing preparation method has the steps for preparing long, difficult to obtain raw materials and high costs weaknesses; preparation and use of organotins on equipment and environmental requirements are high, there is environmental pollution risks. In addition, intermediate B or B ‘structure halogens fluorine and iodine exist, reducing the selective formation of organometallic reagents, so that an increase in side effects, product quality is difficult to be effectively controlled.
Example One:
Under a nitrogen atmosphere, in a three-necked reaction flask was added 2- (2-methyl-tetrazol-5-yl) pyridine-5-boronic acid (II) (2.15g, 10.5mmol) , R-3- (3- fluoro – 4-iodo – phenyl) -2-oxo-5-oxazolidinyl methanol phosphate (III) (4.17g, 10mmol) , tetrakis (triphenylphosphine) palladium (0.23g, 0.2mmol), 1M phosphoric acid 15mL of toluene solution of potassium 30mL, warmed to reflux, maintained the reaction at reflux for 10-12 hours, TLC the reaction was complete. Ethyl acetate was added 30mL, successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, the resulting oil was treated with n-hexane and ethyl acetate (1:1, V / V) was recrystallized, and dried in vacuo to give a white The solid phosphoric acid to Thailand acetazolamide (I) 3.82g, yield% 84.9, 1 the H NMR (of DMSO-d6): D 8.92 (S, IH), 8.20 (m, 2H), 7.74 (T, IH), 7.66 ( dd, 1H), 7.50 (dd , 1H), 4.95 (m, 1H), 4.46 (s, 3H), 4.21 (t, 1H), 4.05 (m, 2H), 3.91 (m, 1H), FAB-MS m / Z: 451 [the m the H +] + .
Example Two:
Under a nitrogen atmosphere, in a three-necked reaction flask was added 2- (2-methyl-tetrazol-5-yl) pyridine-5-boronic acid pinacol ester (II) (3.01g, 10.5mmol), R-3- (3 – fluoro-4-bromo – phenyl) -2-oxo-5-oxazolidinyl methanol phosphate (III) (3.69g, 10mmol), [1,1′- bis (diphenylphosphino) ferrocene Fe] dichloropalladium / dichloromethane complex (0.15g, 0.2mmol), potassium acetate (1.17g, 12mmol) and 1,4-dioxane 50mL, heated to 110 ℃, the reaction was stirred for 4-5 hours , TLC the reaction was complete. Ethyl acetate was added 50mL, successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, the resulting oil was treated with n-hexane and ethyl acetate (1:1, V / V) was recrystallized, and dried in vacuo to give a white Thai solid phosphoric acid to acetazolamide (I) 4.02g, yield 89.3%.
Example Three:
Under a nitrogen atmosphere, in a three-necked reaction flask was added 2- (2-methyl-tetrazol-5-yl) -5-bromo – pyridine (IV) (2.4g, 10mmol), alcohol-based dual which diborane ( 1.27g, 5mmol), 1,1′- bis (diphenylphosphino) ferrocene palladium dichloride (0.82g, 1mmol), potassium acetate (1.17g, 12mmol) and 1,4-dioxane 30mL , heated to 110 deg.] C, the reaction was stirred for 4 hours. Cooled to room temperature, still under nitrogen, was added to the system for R-3- (3- fluoro-4-bromo – phenyl) -2-oxo-5-oxazolidinyl methanol phosphate (III) (3.69 g, 10mmol), 1,4- dioxane and 20mL 5M potassium phosphate 0.5mL, again heated to 100 ℃, the reaction was stirred for 4 hours, TLC the reaction was complete. Ethyl acetate was added 50mL, filtered and the filtrate was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure, the resulting oil was treated with n-hexane and ethyl acetate (1:1, V / V) was recrystallized vacuo Thai dried to give a white solid phosphoric acid to acetazolamide (I) 3.34g, yield 74.2%.
IV (Preparation of the intermediate II) Example:
In a three-necked reaction flask 2- (2-methyl-tetrazol-5-yl) -5-bromo – pyridine (IV) (2.4g, 10mmol) was dissolved in 25mL anhydrous tetrahydrofuran, cooled to -55 deg.] C, was added dropwise isopropylmagnesium chloride (1M, 15ml), dropwise after completion of the reaction was stirred for 30 minutes. To the reaction system was added trimethylborate (1.25g, 12mmol), stirring was continued for 4-5 hours the reaction. At low temperature with saturated ammonium chloride solution to quench the reaction, and the reaction solution was poured into dilute hydrochloric acid and 30mL 1N reaction at room temperature for 1 hour. Extracted three times with ethyl acetate, the combined organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate. Concentrated under reduced pressure, the resulting solid is washed with petroleum ether, and then recrystallized from water to give a white solid of 2- (2-methyl-tetrazol-5-yl) pyridine-5-boronic acid (II) 1.6g, 78.0% yield, m the MS-FAB / Z: 206 [the m the H +] + .
Embodiment 5 (preparation of intermediate II):
In a three-necked reaction flask was added 2- (2-methyl-tetrazol-5-yl) -5-bromo – pyridine (IV) (2.4g, 10mmol) , alcohol-based dual which diborane (1.27g, 5mmol ), 1,1′-bis (diphenylphosphino) ferrocene palladium dichloride (0.82g, 1mmol), potassium acetate (1.17g, 12mmol) and 1,4-dioxane 50mL, heated to 110 ℃, the reaction was stirred for 8-10 hours to complete the reaction by TLC. Extracted three times with ethyl acetate, the combined organic phases were washed with brine, dried over anhydrous sodium sulfate. Concentrated, ethyl acetate and n-hexane (1:4) recrystallized to give an off-white solid 2- (2-methyl-tetrazol-5-yl) pyridine-5-boronic acid pinacol ester (II) 2.48g, yield 86.4 %, the MS-FAB m / Z: 288 [the m the H +] + .
Six (preparation of intermediate III) Example:
Under nitrogen, in a three-necked reaction flask R- glycidyl tosylate (TG) (2.28g, 10mmol) and N, N- dimethylformamide 25mL, stirred and dissolved, was added cesium carbonate (0.33 g, 1mmol) and 3-fluoro-4-bromo – phenyl isocyanate (V) (2.15g, 10mmol) , was heated to 100 ℃, after 1 hour, TLC detection completion of the reaction. Recovery of the solvent under reduced pressure, the residue was dissolved with dichloromethane and water, the organic phase was separated, the aqueous phase was extracted twice with methylene chloride, concentrated under reduced pressure to give an oil which was R-3- (3- fluoro-4-bromo – phenyl) -2-oxo-5-oxazolidinyl methanol p-toluenesulfonate (the VI), without further purification, 1N hydrochloric acid was added directly to the reaction at 50 ℃ 5 hours and extracted three times with dichloromethane The combined organic phase was successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was dissolved in 30mL of triethyl phosphate was added at room temperature, phosphorus oxychloride (2.2mL, 24mmol), stirred for 2-3 hours. 30mL of ethyl acetate was added, stirred for half an hour, poured into 50g of ice-water, and stirring was continued for 2 hours at 0 deg.] C, and a solid white precipitate was filtered, the filter cake washed with acetone and dried to give an off-white solid R-3- (3-fluoro-4-bromo – phenyl) -2-oxo-5-oxazolidinyl methanol phosphate (III) 2.45g, yield 66.4%, FAB-MS m / z: 369 [m + H ] + .
Six (preparation of intermediate III) Example:
Under nitrogen, in a three-necked reaction flask R- glycidyl tosylate (TG) (2.28g, 10mmol) and tetrahydrofuran 50mL, stirred and dissolved, was added lithium iodide (0.14g, 1mmol) and 3- fluoro-4 – phenyl isocyanate (V) (2.63g, 10mmol) , was heated to reflux. after 2 hours, TLC detection completion of the reaction. Recovery of the solvent under reduced pressure, the residue was dissolved with dichloromethane and water, the organic phase was separated, the aqueous phase was extracted twice with methylene chloride, concentrated under reduced pressure to give an oil which was R-3- (3- fluoro-4 – phenyl) -2-oxo-5-oxazolidinyl methanol p-toluenesulfonate (the VI), without further purification, 1N hydrochloric acid was added directly to the reaction at 50 ℃ 5 hours and extracted three times with dichloromethane The combined organic phase was successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was dissolved in 30mL of triethyl phosphate was added at room temperature, phosphorus oxychloride (2.2mL, 24mmol), stirred for 2-3 hours. 30mL of ethyl acetate was added, stirred for half an hour, poured into 50g of ice-water, and stirring was continued for 2 hours at 0 deg.] C, and a solid white precipitate was filtered, the filter cake washed with acetone and dried to give an off-white solid R-3- (3-fluoro-4-iodo – phenyl) -2-oxo-5-oxazolidinyl methanol phosphate (III) 2.65g, yield 63.7%, FAB-MS m / z: 417 [m + H ] + .

//////New Patent, Tedizolid phosphate, Suzhou MiracPharma Technology Co Ltd,  Zheren Pharmaceutical Nanjing Co Ltd, WO 2016058467

TR 700, TR 701FA, Tedizolid phosphate


Figure US08426389-20130423-C00003

“TR-700”

5R)-3-{3-Fluoro-4-[6-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)-pyridin-3-yl]-phenyl}-5-hydroxymethyl-1,3-oxazolidin-2-one

Trius Therapeutics, Inc.

US Patent Publication No. 20070155798, which is hereby incorporated by reference in its entirety, recently disclosed a series of potently anti-bacterial oxazolidinones including

Figure US08426389-20130423-C00001

wherein R═H, PO(OH)2, and PO(ONa)2.

(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate, CAS 856867-55-5

Image for unlabelled figure

DISODIUM SALT

CAS 856867-39-5

  • C17 H16 F N6 O6 P . 2 Na
  • 2-​Oxazolidinone, 3-​[3-​fluoro-​4-​[6-​(2-​methyl-​2H-​tetrazol-​5-​yl)​-​3-​pyridinyl]​phenyl]​-​5-​[(phosphonooxy)​methyl]​-​, sodium salt (1:2)​, (5R)​-
    • DA 7218, Tedizolid phosphate disodium salt

In addition, improved methods of making the free acid are disclosed in U.S. patent application Ser. No. 12/577,089, which is assigned to Trius Therapeutics, Inc., and which is incorporated herein by reference

crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate 1 (R═PO(OH)2), was more stable and non-hygroscopic than the salt forms that were tested. In addition, unlike typical crystallizations, where the crystallization conditions, such as the solvent and temperature conditions, determine the particular crystalline form, the same crystalline form of 1 (R═PO(OH)2) was produced using many solvent and crystallization conditions. Therefore, this crystalline form was very stable, was made reproducibly, and ideal for commercial production because it reduced the chances that other polymorphs would form contaminating impurities during production. However, in all preliminary testing, the free acid crystallized as fine particles, making filtering and processing difficult.

To overcome difficulties in filtering and processing crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate 1 (R═PO(OH)2), processes described herein result in significantly reduced filtering time, avoid more toxic solvents, and significantly increased ease of preparing dosage forms such as tablets. It has been found that implementing various processes can control the particle size distribution of the resulting material, which is useful for making the crystalline form, and for commercial production and pharmaceutical use. Surprisingly, the process for increasing the particle size reduces the amount of the dimer impurity, in comparison to the process for making the free acid disclosed in U.S. patent application Ser. No. 12/577,089. Thus, various methods of making and using the crystalline form are also provided.

In addition, by using methods of making the free acid disclosed in U.S. patent application Ser. No. 12/577,089, which is assigned to the same assignee as in the present application, and by using the crystallization methods described herein, a crystalline free acid having at least 96% purity by weight may be formed that comprises a compound having the following formula:

Figure US08426389-20130423-C00002

(hereinafter “the chloro impurity”), i.e., (R)-5-(chloromethyl)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)oxazolidin-2-one in an amount less than 1%.

Similarly, by using methods of making the free acid disclosed in U.S. patent application Ser. No. 12/577,089, which is assigned to the same assignee as in the present application, and by using the crystallization methods described herein, a crystalline free acid having at least 96% purity by weight may be formed that comprises a compound having the following formula:

Figure US08426389-20130423-C00003

(hereinafter “TR-700”), i.e., 5R)-3-{3-Fluoro-4-[6-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)-pyridin-3-yl]-phenyl}-5-hydroxymethyl-1,3-oxazolidin-2-one, in an amount less than 1%.

The crystalline free acid may have one or more of the attributes described herein.

In some aspects, a purified crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate, i.e., the free acid, has a purity of at least about 96% by weight. In some embodiments, the crystalline free acid has a median volume diameter of at least about 1.0 μm.

BRIEF DESCRIPTION OF THE DRAWINGS……http://www.google.com/patents/US8426389

FIG. 1 the FT-Raman spectrum of crystalline 1 (R═PO(OH)2).

FIG. 2 shows the X-ray powder pattern of crystalline 1 (R═PO(OH)2).

http://www.google.com/patents/US8426389

FIG. 3 shows the differential scanning calorimetry (DSC) thermogram of crystalline 1 (R═PO(OH)2).

http://www.google.com/patents/US8426389

FIG. 4 shows the 1H NMR spectrum of 1 (R═PO(OH)2).

FIG. 5 depicts the TG-FTIR diagram of crystalline 1 (R═PO(OH)2).

http://www.google.com/patents/US8426389

FIG. 6 is a diagram showing the dynamic vapor sorption (DVS) behavior of crystalline 1 (R═PO(OH)2).

FIG. 7 is a manufacturing process schematic for 1 (R═PO(OH)2) (TR-701 FA) in a tablet dosage form.

FIG. 8 is a manufacturing process schematic for 1 (R═PO(OH)2) (TR-701 FA) Compounding Solution for Lyophilization.

FIG. 9 is a manufacturing process schematic for 1 (R═PO(OH)2) (TR-701 FA) for Injection, 200 mg/vial: sterile filtering, filling, and lyophilization.

FIG. 10 is a representative particle size distribution of crystalline free acid without regard to controlling particle size distribution as also described herein.

FIG. 11 is a representative particle size distribution of crystalline free acid made using laboratory processes to control particle size described herein.

FIG. 12 is a representative particle size distribution of crystalline free acid made using scaled up manufacturing processes to control particle size described herein.

 

These impurities include

Figure US08426389-20130423-C00004

i.e., 5R)-3-{3-Fluoro-4-[6-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)-pyridin-3-yl]-phenyl}-5-hydroxymethyl-1,3-oxazolidin-2-one (“TR-700”) and/or

Figure US08426389-20130423-C00005

i.e., (R)-5-(chloromethyl)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)phenyl)oxazolidin-2-one (“chloro impurity”).

 

Cited Patent Filing date Publication date Applicant Title
US4128654 Feb 10, 1978 Dec 5, 1978 E. I. Du Pont De Nemours And Company 5-Halomethyl-3-phenyl-2-oxazolidinones
US4250318 Aug 9, 1978 Feb 10, 1981 Delalande S.A. Novel 5-hydroxymethyl oxazolidinones, the method of preparing them and their application in therapeutics
US4340606 Oct 23, 1980 Jul 20, 1982 E. I. Du Pont De Nemours And Company 3-(p-Alkylsulfonylphenyl)oxazolidinone derivatives as antibacterial agents
US4461773 Jan 5, 1984 Jul 24, 1984 E. I. Dupont De Nemours And Company P-Oxooxazolidinylbenzene compounds as antibacterial agents
US4476136 Feb 24, 1982 Oct 9, 1984 Delalande S.A. Aminomethyl-5 oxazolidinic derivatives and therapeutic use thereof
US4948801 Jul 29, 1988 Aug 14, 1990 E. I. Du Pont De Nemours And Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
US5523403 May 22, 1995 Jun 4, 1996 The Upjohn Company Tropone-substituted phenyloxazolidinone antibacterial agents
US5565571 Apr 28, 1994 Oct 15, 1996 The Upjohn Company Substituted aryl- and heteroaryl-phenyloxazolidinones
US5652238 Sep 27, 1994 Jul 29, 1997 Pharmacia & Upjohn Company Esters of substituted-hydroxyacetyl piperazine phenyl oxazolidinones
US5688792 Aug 16, 1994 Nov 18, 1997 Pharmacia & Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
US6365751 Apr 17, 2001 Apr 2, 2002 Zeneca Ltd. Antibiotic oxazolidinone derivatives
US6627646 * Jul 17, 2001 Sep 30, 2003 Sepracor Inc. Norastemizole polymorphs
US6689779 May 18, 2001 Feb 10, 2004 Dong A Pharm. Co., Ltd. Oxazolidinone derivatives and a process for the preparation thereof
US7129259 Dec 1, 2004 Oct 31, 2006 Rib-X Pharmaceuticals, Inc. Halogenated biaryl heterocyclic compounds and methods of making and using the same
US7141583 Apr 23, 2001 Nov 28, 2006 Astrazeneca Ab Oxazolidinone derivatives with antibiotic activity
US7144911 Dec 24, 2003 Dec 5, 2006 Deciphera Pharmaceuticals Llc Anti-inflammatory medicaments
US7202257 Jul 6, 2004 Apr 10, 2007 Deciphera Pharmaceuticals, Llc Anti-inflammatory medicaments
US7396847 Sep 9, 2002 Jul 8, 2008 Astrazeneca Ab Oxazolidinone and/or isoxazoline as antibacterial agents
US7462633 Jun 29, 2004 Dec 9, 2008 Merck & Co., Inc. Cyclopropyl group substituted oxazolidinone antibiotics and derivatives thereof
US7473699 Feb 25, 2003 Jan 6, 2009 Astrazeneca Ab 3-cyclyl-5-(nitrogen-containing 5-membered ring)methyl-oxazolidinone derivatives and their use as antibacterial agents
US7498350 Nov 24, 2003 Mar 3, 2009 Astrazeneca Ab Oxazolidinones as antibacterial agents
US7816379 Dec 17, 2004 Oct 19, 2010 Dong-A Pharm. Co., Ltd. Oxazolidinone derivatives
US20020115669 Aug 29, 2001 Aug 22, 2002 Wiedeman Paul E. Oxazolidinone chemotherapeutic agents
US20030166620 May 18, 2001 Sep 4, 2003 Jae-Gul Lee Novel oxazolidinone derivatives and a process for the preparation thereof
US20040180906 Dec 24, 2003 Sep 16, 2004 Flynn Daniel L Anti-inflammatory medicaments
US20050038092 Jun 29, 2004 Feb 17, 2005 Yasumichi Fukuda Cyclopropyl group substituted oxazolidinone antibiotics and derivatives thereof
US20050107435 Sep 9, 2002 May 19, 2005 Gravestock Michael B. Oxazolidinone and/or isoxazoline as antibacterial agents
US20050288286 Jul 6, 2004 Dec 29, 2005 Flynn Daniel L Anti-inflammatory medicaments
US20060116386 Nov 24, 2003 Jun 1, 2006 Astrazeneca Ab Oxazolidinones as antibacterial agents
US20060116400 Nov 24, 2003 Jun 1, 2006 Astrazeneca Ab Oxazolidinone and/or isoxazoline derivatives as antibacterial agents
US20060270637 Feb 24, 2004 Nov 30, 2006 Astrazeneca Ab Hydroxymethyl substituted dihydroisoxazole derivatives useful as antibiotic agents
US20070155798 Dec 17, 2004 Jul 5, 2007 Dong-A Pharm. Co., Ltd. Novel oxazolidinone derivatives
US20070185132 Jun 29, 2004 Aug 9, 2007 Yasumichi Fukuda Cyclopropyl group substituted oxazolidinone antibiotics and derivatives thereo
US20070191336 Dec 23, 2004 Aug 16, 2007 Flynn Daniel L Anti-inflammatory medicaments
US20070203187 Jan 22, 2007 Aug 30, 2007 Merck & Co., Inc. Cyclopropyl group substituted oxazolidinone antibiotics and derivatives thereof
US20070208062 May 24, 2005 Sep 6, 2007 Astrazeneca Ab 3-(4-(2-dihydroisoxazol-3-ylpyridin-5-yl)phenyl)-5-triazol-1-ylmethyloxazolidin-2-one derivatives as mao inhibitors for the treatment of bacterial infections
US20080021012 May 24, 2005 Jan 24, 2008 Astrazeneca Ab 3-[4-{6-Substituted Alkanoyl Pyridin-3-Yl}-3-Phenyl]-5-(1H-1,2,3-Triazol-1-Ylmethyl)-1,3-Oxazolidin-2-Ones As Antibacterial Agents
US20080021071 May 24, 2005 Jan 24, 2008 Astrazeneca Ab 3-{4-(Pyridin-3-Yl) Phenyl}-5-(1H-1,2,3-Triazol-1-Ylmethyl)-1,3-Oxazolidin-2-Ones as Antibacterial Agents
US20080064689 May 24, 2004 Mar 13, 2008 Astrazeneca Ab 3-[4-(6-Pyridin-3-Yl)-3-Phenyl] -5-(1H-1,2,3-Triazol-1-Ylmethyl)-1,3-Oxazolidin-2-Ones as Antibacterial Agents
US20090018123 Jun 19, 2006 Jan 15, 2009 Milind D Sindkhedkar Oxazolidinones Bearing Antimicrobial Activity Composition and Methods of Preparation
US20090192197 Jul 30, 2009 Dong-A Pharm. Co., Ltd. Novel oxazolidinone derivatives
US20100093669 Oct 9, 2009 Apr 15, 2010 Trius Therapeutics Methods for preparing oxazolidinones and compositions containing them
US20100227839 Sep 9, 2010 Trius Therapeutics Crystalline form of r)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin- 5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate
AU2004299413A1 Title not available
AU2009200606A1 Title not available
CA2549062A1 Dec 17, 2004 Jun 30, 2005 Dong-A Pharm. Co., Ltd. Novel oxazolidinone derivatives
CN101982468A Dec 17, 2004 Mar 2, 2011 东亚制药株式会社 Novel oxazolidinone derivatives and pharmaceutical compositions comprising the derivatives
EP0312000A1 Oct 12, 1988 Apr 19, 1989 The Du Pont Merck Pharmaceutical Company Aminomethyl oxooxazolidinyl aroylbenzene derivatives useful as antibacterial agents
EP0352781A2 Jul 27, 1989 Jan 31, 1990 The Du Pont Merck Pharmaceutical Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
EP1699784A1 Dec 17, 2004 Sep 13, 2006 Dong-A Pharmaceutical Co., Ltd. Novel oxazolidinone derivatives
EP2305657A2 Dec 17, 2004 Apr 6, 2011 Dong-A Pharmaceutical Co., Ltd. Oxazolidinone derivatives
EP2435051A1 May 27, 2010 Apr 4, 2012 Trius Therapeutics Oxazolidinone containing dimer compounds, compositions and methods to make and use
IN236862A1 Title not available
JPS5799576A Title not available
KR20110071107A Title not available
NZ547928A Title not available
NZ575842A Title not available
WO1993009103A1 Oct 5, 1992 May 13, 1993 Upjohn Co Substituted aryl- and heteroarylphenyloxazolidinones useful as antibacterial agents
WO1993023384A1 Apr 21, 1993 Nov 25, 1993 Upjohn Co Oxazolidinones containing a substituted diazine moiety and their use as antimicrobials
WO1995007271A1 Aug 16, 1994 Mar 16, 1995 Michael R Barbachyn Substituted oxazine and thiazine oxazolidinone antimicrobials
WO1995014684A1 Sep 27, 1994 Jun 1, 1995 Michel R Barbachyn Esters of substituted-hydroxyacetyl piperazine phenyl oxazolidinones
WO2001094342A1 May 18, 2001 Dec 13, 2001 Cho Jong Hwan Novel oxazolidinone derivatives and a process for the preparation thereof
WO2002081470A1 Apr 3, 2002 Oct 17, 2002 Astrazeneca Ab Oxazolidinones containing a sulfonimid group as antibiotics
WO2003022824A1 Sep 9, 2002 Mar 20, 2003 Astrazeneca Ab Oxazolidinone and/or isoxazoline as antibacterial agents
WO2003035648A1 Oct 23, 2002 May 1, 2003 Astrazeneca Ab Aryl substituted oxazolidinones with antibacterial activity
WO2003047358A1 Dec 2, 2002 Jun 12, 2003 Vaughan Leslie Crow Cheese flavour ingredient and method of its production
WO2003072575A1 Feb 25, 2003 Sep 4, 2003 Astrazeneca Ab 3-cyclyl-5-(nitrogen-containing 5-membered ring) methyl-oxazolidinone derivatives and their use as antibacterial agents
WO2003072576A2 Feb 25, 2003 Sep 4, 2003 Astrazeneca Ab Oxazolidinone derivatives, processes for their preparation, and pharmaceutical compositions containing them
WO2004048350A2 Nov 24, 2003 Jun 10, 2004 Astrazeneca Ab Oxazolidinones as antibacterial agents
WO2004083205A1 Mar 16, 2004 Sep 30, 2004 Astrazeneca Ab Antibacterial 1, 3- oxazolidin -2- one derivatives
WO2005005398A2 Jun 29, 2004 Jan 20, 2005 Yasumichi Fukuda Cyclopropyl group substituted oxazolidinone antibiotics and derivatives thereof
WO2005051933A1 Nov 23, 2004 Jun 9, 2005 Vijay Kumar Kaul An improved process for the synthesis of 4-(4-benzyloxy-carbonylamino-2-fluorophenyl)-piperazine-1-carboxylic acid tert-butyl ester, a key intermediate for oxazolidinone antimicrobials and compounds prepared thereby
WO2005058886A1 Dec 17, 2004 Jun 30, 2005 Dong A Pharm Co Ltd Novel oxazolidinone derivatives
WO2005116017A1 May 24, 2005 Dec 8, 2005 Astrazeneca Ab Process for the preparation of aryl substituted oxazolidinones as intermediates for antibacterial agents
WO2006038100A1 Oct 6, 2005 Apr 13, 2006 Ranbaxy Lab Ltd Oxazolidinone derivatives as antimicrobials
WO2007023507A2 Jun 19, 2006 Mar 1, 2007 Milind D Sindkhedkar Oxazolidinones bearing antimicrobial activity composition and methods of preparation
WO2007138381A2 Oct 13, 2006 Dec 6, 2007 Delorme Daniel Phosphonated oxazolidinones and uses thereof for the prevention and treatment of bone and joint infections
WO2010042887A2 Oct 9, 2009 Apr 15, 2010 Trius Therapeutics Methods for preparing oxazolidinones and compositions containing them
WO2010091131A1 Feb 3, 2010 Aug 12, 2010 Trius Therapeutics Crystalline form of r)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate
WO2010138649A1 May 27, 2010 Dec 2, 2010 Trius Therapeutics, Inc. Oxazolidinone containing dimer compounds, compositions and methods to make and use
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