VORICONAZOLE
CAS 137234-62-9
(2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol
Voriconazole (vor-i-KON-a-zole, brand name Vfend, Pfizer) is a triazole antifungal medication that is generally used to treat serious, invasive fungal infections. These are generally seen in patients who are immunocompromised, and include invasive candidiasis, invasive aspergillosis, and certain emerging fungal infections
1H NMR......... http://file.selleckchem.com/downloads/nmr/S144202-Voriconazole-HNMR-Selleck.pdf
1H NMR DMSO-d6, peak at 3.3 is HOD
13 C NMR
DMSO-d6
CAS 137234-62-9
(2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol
| Chemical Names: | Voriconazole; Vfend; 137234-62-9; UK-109496; Voriconazol; Voriconazolum |
|---|---|
CAS 137234-62-9
(aR,bS)-a-(2,4-Difluorophenyl)-5-fluoro-b-methyl-a-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimideethanol
2R,3S-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
Manufacturers' Codes: UK-109496
Trademarks: Vfend (Pfizer)
MF: C16H14F3N5O
MW: 349.31
Percent Composition: C 55.01%, H 4.04%, F 16.32%, N 20.05%, O 4.58%
Properties: mp 127°. [a]D25 -62° (c = 1 in methanol).
Melting point: mp 127°
Optical Rotation: [a]D25 -62° (c = 1 in methanol)
Therap-Cat: Antifungal (systemic)
|
Voriconazole (vor-i-KON-a-zole, brand name Vfend, Pfizer) is a triazole antifungal medication that is generally used to treat serious, invasive fungal infections. These are generally seen in patients who are immunocompromised, and include invasive candidiasis, invasive aspergillosis, and certain emerging fungal infections
1H NMR......... http://file.selleckchem.com/downloads/nmr/S144202-Voriconazole-HNMR-Selleck.pdf
1H NMR DMSO-d6, peak at 3.3 is HOD
m.p=134
1H-NMR (300 MHz, DMSO-d6) δ
(ppm):
9.04 (1H),
8.84 (1H),
8.23 (1H),
7.61 (1H),
7.28 (1H),
7.17 (1H),
6.91 (1H),
5.97 (1H),
4.80 (1H),
4.34 (1H),
3.93 (1H),
1.1 (3H).............US8263769
9.04 (1H),
8.84 (1H),
8.23 (1H),
7.61 (1H),
7.28 (1H),
7.17 (1H),
6.91 (1H),
5.97 (1H),
4.80 (1H),
4.34 (1H),
3.93 (1H),
1.1 (3H).............US8263769
13 C NMR
DMSO-d6
1H NMR PREDICT
13C NMR PREDICT
COSY PREDICT
HMBC PREDICT
HPLC
To date, only two methods for preparing voriconazole have been reported. One is based on a coupling reaction using an organic lithium salt, and the other, on Reformatsky-type coupling reaction.
For example, Korean Patent No. 1993-0011039 and European Patent No. 0,440,372 disclose a method shown in Reaction Scheme A for preparing the desired enantiomeric pair by a) adding an organic lithium derivative of 4-chloro-6-ethyl-5-fluoropyrimidine to 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone at −70° C.˜−50° C. to obtain an enantiomer mixture; and b) separating the desired enantiomer by chromatography.
PCT Publication No. WO 2006/065726 discloses a method shown in Reaction Scheme B for preparing the desired enantiomeric pair by repeating the procedure of Reaction Scheme A except for using a different solvent.
In order to solve the problems, as shown in Reaction Scheme C, Korean Patent Publication No. 1999-0036174 and U.S. Pat. No. 6,586,594 B1 disclose a method for preparing voriconazole by conducting Reformatsky-type reaction to enhance the stereoselectivity and yield, and then reductively removing the chlorine substituent in the presence of a palladium catalyst.
Further, the literature ([Organic Process Research & Development 2001, 5, 28-36], Pfizer Inc.) teaches that the chlorine substituent of the pyrimidine derivative adversely influences the coupling reaction pattern as shown in Reaction Scheme D and Table 1.
| TABLE 1 | ||||||
| Reformatsky-type reaction of compounds (VI, VII) and (IV) | ||||||
| Compound | Compound | Unreacted | Debrominated | Compound | Compound | |
| Pyrimidine | (VIII) (%) | (IX) (%) | pyrimidine (%) | pyrimidine (%) | (X) (%) | (XI) (%) |
| Compound | 47.5 | 24.0 | 0.0 | 15 | 4.3 | 9.2 |
| (VI) | ||||||
| Compound | 5.3 | 4.6 | 8.5 | 28 | 0.0 | 51.6 |
| (VII) | ||||||
MORE..................
In the synthesis of Voriconazole, it is
thought that two important steps are step i) of preparing the pyrimidine
derivative as an intermediate for use in the subsequent coupling
reaction with high yield and high purity, and step ii) of increasing
stereoselectivity in carrying out the coupling reaction between the
pyrimidine derivative and the ketone derivative to obtain the resultant
tertiary alcohol with high purity and high yield.
First, the pyrimidine derivative has been
prepared as depicted in the following Reaction Scheme 1 under reflux
without any solvent according to Korean Patent No. 1993-0011039 and EP
0440372. It is reported that the yield of pyrimidine derivative is as
low as 66%. However, the method of Reaction Scheme 1 is not suitable for
mass production owing to its severe reaction condition and low yield.
In addition, Korean Patent No. 10-0269048
and EP 0871625 disclose that the pyrimidine derivative is prepared via
the method of Reaction Scheme 1 in the presence of a solvent, and the
yield of the target product is 90%. However, in this case, there are
problems in that phosphoryl chloride used in an excessive amount is
hardly removed and the resultant product has low purity.
Meanwhile, Korean Unexamined Patent
Publication No. 10-2009-0014468 discloses a process for preparing
substituted thiopyrimidine derivatives by introducing a thiol group to a
pyrimidine derivative, as shown in the following Reaction Scheme 2, to
increase the purity of the pyrimidine derivative.
However, the above process is not amenable
to industrial mass production due to the increased number of steps as
compared to Reaction Scheme 1, the use of expensive thiol derivatives,
and the bad odor generated during the step using thiol. Next, Korean
Patent No. 1993-0011039 and EP 0440372 disclose processes for carrying
out a coupling reaction between pyrimidine derivatives and ketone
derivatives. Herein, as shown in the following Reaction Scheme 3, LDA
(lithium diisopropylamide), a strong base, or sodium
bis(trimethylsilyl)amide is used to perform the coupling reaction.
However, the above methods are problematic
in that they use highly explosive strong bases and require equipment
capable of cryogenic reaction. Above all, the methods provide very low
yield due to the low stereoselectivity and difficulty in separating
isomers, and thus are not amenable to mass production.
To overcome the above-mentioned problems,
Korean Patent No. 10-0269048 and EP 0871625 disclose a method by which
the stereoselectivity is increased through the Reformatsky-type coupling
reaction as depicted in the following Reaction Scheme 4, and
enantiomeric pairs (2R,3S/2S,3R) are separated in the form of their
hydrochloride salts via crystallization, thereby increasing the yield.
However, the method is problematic in that
it results in a relatively low yield of 65% despite a high ratio of the
enantiomeric pairs of 9:1 (2R,3S/2S,3R:2R,3R/2S,3S).
The method has another problem related to the removal of halo after the hydrochloride salts are treated with base.
EP 0069442 discloses a method for
preparing 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone, one
of the main intermediates of Voriconazole, according to the following
Reaction Scheme 5.
However, the above method provides a low yield of 40%.
..............................
Scheme E.
Example 7
Preparation of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butane-2-ol(voriconazole)
10 g of
(2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butane-2-ol
(R)-camsylate obtained in Example 6 was added to a mixture of 50 ml of
water and 50 ml of dichloromethane, and a 40% sodium hydroxide solution
was slowly added thereto to adjust the pH to 11˜12. The organic layer
was separated therefrom and dried over magnesium sulfate, and the
organic solvent was removed under a reduced pressure. The resulting
solution was crystallized with 18 ml of isopropanol, cooled to 0° C.,
stirred for 2 hours, and dried to obtain the white title compound (5.56
g, yield: 93%).
m.p=134
1H-NMR (300 MHz, DMSO-d6) δ
(ppm): 9.04 (1H), 8.84 (1H), 8.23 (1H), 7.61 (1H), 7.28 (1H), 7.17 (1H),
6.91 (1H), 5.97 (1H), 4.80 (1H), 4.34 (1H), 3.93 (1H), 1.1 (3H)
The optical purity of the compound obtained from HPLC analysis was >99.9%.
Comparative Example
Preparation of
(2R,3S)/(2S,3R)-(2R,3R)/(2S,3S)-3-(4-chloro-5-fluoropyrimidine-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butane-2-ol
hydrochloride
5.29 g of zinc powder treated with 1N HCl and 0.26 g
of lead powder were added to 33.5 ml of tetrahydrofuran and stirred,
and 3.98 g of iodine dissolved in 10.6 ml of tetrahydrofuran was slowly
added thereto for 10 min while heating to 45° C. The resulting mixture
was cooled to 2° C., and a solution dissolving 3.53 g of
1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone in 30 ml of
tetrahydrofuran, 5 g of 6-(1-bromo-ethyl)-4-chloro-5-fluoropyrimidine
and 0.32 g of iodine were slowly added thereto for 10 min. The obtained
mixture was heated to 25° C. and reacted for 1 hour.
4.67 g of glacial acetic acid and 12 ml of water
were added to the reaction solution, solid metal residue was filtered
out, and tetrahydrofuran was removed under a reduced pressure.
The resulting residue was extracted twice with 66 ml
of ethyl acetate, and the extract was successively washed with 4.67 g
of disodium ethylenediaminetetraacetate dehydrate dissolved in 12 ml of
water, and 30 ml of brine. The organic layer was concentrated to 40 ml
volume, and 0.86 g of HCl dissolved in 4.3 ml of isopropanol was added
thereto at 25° C.
The obtained crystal was filtrated, washed with 10
ml of ethyl acetate, and dried to obtain the title compound as a yellow
crystal (2.81 g, yield: 42%).
m.p=126˜130° C.
1H-NMR (300 MHz, DMSO-d6) δ (ppm): 8.84 (1H), 8.73 (1H), 7.93 (1H), 7.28 (1H), 7.20 (1H), 6.91 (1H), 4.82 (1H), 4.54 (1H), 3.93 (1H), 1.14 (3H)
The enantiomer ratio obtained from HPLC analysis of
the reaction solution by using an internal standard material was 10:1,
and 14.39% of unknown byproduct was formed. Further, the ratio of
(2R,3S)/(2S,3R)- and (2R,3R)/(2S,3S)-enantiomeric pair obtained from
HPLC analysis of the crystallized hydrochloride was 94.4%:4.8%.
.........................Patent WO2007132354A2
..................
http://www.google.co.in/patents/WO2009024214A1?cl=en
Example 18
(2R.3S)-2-(2.4-Difluorophenvn-3-(5-fluoropyrimidin-4-yl)-1 -d H-1.2.4-triazol-
1-yl)butan-2-ol (voriconazole), compound of Formula (\) To a solution of the racemic material as obtained in example 15 (1.28 g, 3.66 mmol) in acetone (29 ml) was added a solution of (1R)-10-camphorsulfonic acid (0.85 g, 3.66 mmol) in methanol (9.6 ml). The solvents were removed at reduced pressure, and the residue was dissolved in a mixture of acetone (10 ml) and methanol (2 ml). Crystals formed spontaneously after 3 h. Acetone (10 ml) was added, and the mixture was stirred overnight. The solid was isolated by filtration, washed with a small amount of acetone and dried. The solid was dissolved in a mixture of acetone (14 ml) and methanol (4 ml) at reflux. The solution was cooled to rt and stirred for 90 min. Isolation of the precipitate formed by filtration, washing with acetone and drying afforded 0.72 g of the acid addition salt. 0.70 g of the solid material was taken up in dichloromethane (10 ml) and water (10 ml), and the pH was adjusted to 11 by addition of aqueous sodium hydroxide (15% sol.). The layers were separated, and the aqueous layer was extracted with dichloromethane (5 ml). The combined organic layers were washed with water (3 x 10 ml) and brine, and dried (sodium sulfate). Concentration at reduced pressure afforded 0.36 g (28% yield, 56% of the available enantiomer) of voriconazole as a white crystalline solid. Purity, HPLC: 99.8% (RT=4.91 min). Mp. 122.6 0C (Lit. 134 0C). MS, m/z (% rel. int.): 224.0 (27), 350.1 (100), 391.0 (10). 1H NMR (600 MHz, DMSO-d6): δ 9.02 (1H, d, J 3.0 Hz)1 8.83 (1 H1 d, J 1.8 Hz), 8.21 (1 H1 s), 7.59 (1 H1 s), 7.24 (1H1 ddd, J 7.0 Hz, J 9.0 Hz, J 9.0 Hz), 7.16 (1H, ddd, J 2.4 Hz, J 9.0 Hz, J 11.8 Hz), 6.89 (1H, ddd, J 2.4 Hz, J 8.4 Hz, J 8.4 Hz), 5.95 (1 H, s), 4.77 (1 H, d, J 14.4 Hz), 4.31 (1H, d, J 14.4 Hz), 3.90 (1 H, q, J 7.0 Hz), 1.08 (3H1 d, J 7.0 Hz).
Example 19
(2R.3S)-2-(2.4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1 -d H-1.2.4-triazol-
1 -yl)butan-2-ol (voriconazole), compound of Formula (I) (2R,3S)-2-(2,4-Difluorophenyl)-3-[5-fluoropyrimidin-4-yl]-1-(1 H-1 ,2,4-triazol- 1-yl)butan-2- ol (R)-10-camphorsulfonate (656 g, 1.13 mol) was parted between dichloromethane (3 L) and water (3 L), and the pH of the aqueous phase was slowly adjusted to pH 12.3 with aqueous sodium hydroxide (40% w/v, 130 mL). The phases were separated, and the aqueous layer was extracted with dichloromethane (1 L). The combined organic layers were washed with water (3 x 1.5 L) and filtered. The solvent was changed to isopropanol (1.3 L) via gradual addition/evaporation at reduced pressure. After stirring for 3 h at 20 0C, the temperature was lowered to -5 0C. The mixture was stirred for another 1.5 h, and the product was isolated by suction filtration, washed with isopropanol (0.3 L) and dried at 20 0C and vacuum for 2.5 days. 285 g (72% yield) of the title compound was obtained as a white solid. Purity, HPLC: 99.8%. Optical purity, HPLC: >99.9%. 1H NMR (300 MHz, DMSO-d6): δ 9.05 (1H1 d, J 3.0 Hz), 8.86 (1H1 d, J 1.8 Hz), 8.24 (1H, s), 7.62 (1H, s), 7.24 (2H, m), 6.92 (1H, dt, J 2.1, 8.0 Hz), 5.99 (1H, s), 4.81 (1H1 d, J 14.1 Hz), 4.34 (1H1 d, J 14.4 Hz), 3.93 (1H, q, J 7.2 Hz), 1.11 (3H1 d, J 6.9 Hz). 13C NMR spectrum and IR spectrum for the isolated compound are attached.
......................
PAPER
PAPER
J. Org. Chem., 2013, 78 (22), pp 11396–11403
DOI: 10.1021/jo4019528
..........................
Org. Proc. Res. Dev., 2001, 5 (1), pp 28–36
DOI: 10.1021/op0000879
(2R,3S)-2-(2,4-Difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (1). ...............to provide the title compound as a white solid (7.6 g, 40% mass yield or 80% of available enantiomer), mp 134 °C
1H NMR (DMSO-d6) δ 1.1 (d, 3H), 3.93 (q, 1H), 4.34 (d, 1H), 4.80 (d, 1H), 5.97 (bs, 1H), 6.91 (ddd, 1H), 7.17 (ddd, 1H), 7.28 (ddd, 1H), 7.61 (s, 1H), 8.23 (s, 1H), 8.84 (s, 1H), 9.04 (s, 1H) ppm.
| Cited Patent | Filing date | Publication date | Applicant | Title |
|---|---|---|---|---|
| US6586594 | 26 Jul 1996 | 1 Jul 2003 | Pfizer, Inc. | Preparation of triazoles by organometallic addition to ketones and intermediates therefor |
| CN1488630A | 8 Oct 2002 | 14 Apr 2004 | 张文更 | Method for preparing triazole antifungal agent |
| CN1814597A | 9 Dec 2005 | 9 Aug 2006 | 北京丰德医药科技有限公司 | New method for preparing voriconazole |
| EP0440372A1 | 24 Jan 1991 | 7 Aug 1991 | Pfizer Limited | Triazole antifungal agents |
| GB2452049A | Title not available | |||
| WO1993007139A1 | 1 Oct 1992 | 15 Apr 1993 | Pfizer Ltd | Triazole antifungal agents |
| WO1997006160A1 | 26 Jul 1996 | 20 Feb 1997 | Michael Butters | Preparation of triazoles by organometallic addition to ketones and intermediates therefor |
| WO2006065726A2 | 13 Dec 2005 | 22 Jun 2006 | Reddys Lab Ltd Dr | Process for preparing voriconazole |
| WO2007013096A1 | 26 Jun 2006 | 1 Feb 2007 | Msn Lab Ltd | Improved process for the preparation of 2r, 3s-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol (voriconazole) |
| WO2007132354A2 | 29 Jan 2007 | 22 Nov 2007 | Medichem Sa | Process for preparing voriconazole, new polymorphic form of intermediate thereof, and uses thereof |
| WO2009024214A1 * | 10 Jul 2008 | 26 Feb 2009 | Axellia Pharmaceuticals Aps | Process for the production of voriconazole |
| WO2009084029A2 | 2 Dec 2008 | 9 Jul 2009 | Venkatesh Bhingolikar | Improved process for the preparation of (2r,3s)-2-(2,4- difluqrophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol |
| US8575344 * | 1 Feb 2011 | 5 Nov 2013 | Dongkook Pharmaceutical Co., Ltd. | Process for preparing voriconazole by using new intermediates |
| US20130005973 * | 1 Feb 2011 | 3 Jan 2013 | Dongkook Pharmaceutical Co., Ltd. | Process for preparing voriconazole by using new intermediates |
| |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Butters et al., "Process Development of Voriconazole: A Novel Broad-Spectrum Triazole Antifungal Agent," Organic Process Research & Development, 2001, vol. 5, pp. 28-36. | ||||||||||||||||||||||||||||||||||||
References:
Ergosterol biosynthesis inhibitor. Prepn: S. J. Ray, K. Richardson, EP 440372; eidem, US 5278175 (1991, 1994 both to Pfizer); R. P. Dickinson et al., Bioorg. Med. Chem. Lett. 6, 2031 (1996).
Mechanism of action: H. Sanati et al.,Antimicrob. Agents Chemother. 41, 2492 (1997). In vitro antifungal spectrum: F. Marco et al., ibid. 42, 161 (1998).
HPLC determn in plasma: R. Gage, D. A. Stopher, J. Pharm. Biomed. Anal. 17, 1449 (1998).
Review of pharmacology and clinical development: P. E. Verweij et al., Curr. Opin. Anti-Infect. Invest. Drugs 1, 361-372 (1999); J. A. Sabo, S. M. Abdel-Rahman, Ann. Pharmacother. 34, 1032-1043 (2000).
Clinical pharmacokinetics: L. Purkins et al., Antimicrob. Agents Chemother. 46, 2546 (2002).
Clinical comparison with amphotericin B: T. J. Walsh et al., N. Engl. J. Med. 346, 225 (2002).
MOLFILE FOR STRUCTURE..........COPY THE CENTERED CODE IN BLUE
START
64684.molChemDraw07261512442D
26 28 0 0 0 0 0 0 0 0999 V2000
0.5118 1.1267 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.2030 0.7149 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.9179 0.3031 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
-0.6206 1.4298 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.2030 2.1447 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
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-1.8559 2.1447 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.4441 1.4298 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
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0.2088 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.5062 -0.4117 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0
0.9236 0.4118 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.9236 1.2411 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
1.5928 1.7215 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.3354 2.5107 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.5118 2.5107 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.2545 1.7215 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0
0.6205 -0.7149 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.2088 -1.4297 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.6205 -2.1446 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.4440 -2.1446 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.8559 -2.8595 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
1.8559 -1.4297 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.4440 -0.7149 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.8559 0.0000 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
2 3 1 1
2 4 1 0
2 11 1 0
4 5 1 0
4 9 2 0
5 6 2 0
6 7 1 0
7 8 2 0
8 9 1 0
9 10 1 0
11 12 1 1
11 13 1 0
11 19 1 0
13 14 1 0
14 15 1 0
14 18 1 0
15 16 2 0
16 17 1 0
17 18 2 0
19 20 1 0
19 25 2 0
20 21 2 0
21 22 1 0
22 23 1 0
22 24 2 0
24 25 1 0
25 26 1 0
M END
END
 |
|
 |
|
| Systematic (IUPAC) name | |
|---|---|
(2R,3S)-2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
|
|
| Clinical data | |
| Trade names | VFEND |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a605022 |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy category |
|
| Legal status |
|
| Routes of administration |
IV, oral |
| Pharmacokinetic data | |
| Bioavailability | 96% |
| Protein binding | 58% |
| Metabolism | Hepatic cytochrome P450 enzymes CYP2C19, CYP2C9, CYP3A4 |
| Biological half-life | Dose-dependent |
| Identifiers | |
| CAS Registry Number | 137234-62-9  |
| ATC code | J02AC03 |
| PubChem | CID: 71616 |
| DrugBank | DB00582 |
| ChemSpider | 64684 |
| UNII | JFU09I87TR |
| KEGG | D00578 |
| ChEBI | CHEBI:10023 |
| ChEMBL | CHEMBL638 |
| Chemical data | |
| Formula | C16H14F3N5O |
| Molecular mass | 349.311 g/mol |
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