Method of producing 2-amino-3-ethoxycarbonylamino-6-(n-fluorobenzylamino)-pyridine gluconate

专利摘要:

公开号:SU1398772A3
申请号:SU853884101
申请日:1985-04-26
公开日:1988-05-23
发明作者:Хеттхе Хельмут；Эмиг Петер；Энгель Юрген
申请人:Дегусса Аг (Фирма)；
IPC主号:

专利说明:

(21) 3884101 / 23-04
(22) 04/26/85
(31) P 3416609.2
(32) 05.05.84
(33) DE
(46) 05.23.88. Bul No. 19
(7) Degussa AG (DE)
(72) Helmut Hetthe, Peter Emig
and Jürgen Engel (DE)
(53) 547,822.2.07 (088.8)
(56) Patent of Germany No. 1670522,
cl. C 07 D 213/75, 1978.
Patent of Germany No. 1795858, cl. C 07 D 213/75, 1979.
Patent. USSR № 1091855, cl. C 07 D 213/75. 10.09.81.
(54) METHOD FOR PREPARING 2-A SHNO-3-ETOXYCARBONYLAMINO-6- (p-FLUTORBENZYL-AMINO) -PYRIDINGHYLONCONATE - (p-fluorobenzylamino) -pyridine gluconate, which has anti-inflammatory and analgesic effects. The goal is to develop a method for obtaining new compounds with these properties. The preparation of the target compound is carried out from 2-amino-3-ethoxycarbonylamino-6- (p-fluorobenzylamino) -pyridine, which is reacted with gluconic acid with either cG-lactone gluconic acid in a mixture of solvent and water at 40-90 C. 2 Il. tab.
§
U)
with
with so
00
J m
HS

cm
113987722
This invention relates to novel quino-3-ethoxycarbonylamino-6- (p-fluoric compounds, namely, a pyridine derivative, gluconate-2-amiF; CH2-NH
possessing anti-inflammatory and analgesic effects.
The purpose of the invention is to create, on the basis of known methods, a method of obtaining a new compound with valuable pharmacological properties.
Figures / 1 and 2 show IR spectra in KBG.
Example 1, 3.043 g (0.01 mol) of 2-amino-3-ethoxycarbonylamino-6- (p-fluorobenzylamino) -pyridine is suspended in 10 ml of absolute ethanol under a nitrogen atmosphere and mixed with the solution prepared at 1.731 for 30 minutes g (0.01 mol) of 5-lactone of gluconic acid in 10 ml of water. Heat for about 15 minutes until a clear solution is obtained and then evaporated in vacuo to dryness. The residue with 10 ml of absolute ethanol is continued to evaporate and dried under vacuum at 50 ° C.
Yield 4.33 g (90% of theory) of flupirtin gluconate (2-amino-3-ztoxycarbonylamino-6- (n fluorobenzylamino) - pyridine gluconate), t. Pl. 117-123 C. Solubility in water is about 0.01% at 25 g.
The IR spectrum in KBG ::. Is shown in FIG. 1 and 2..
Example 2. 3.043 g (0.01 mol) of 2-amino-3-ethoxycarbonylamino-6- (p-fluorobenzylamino) -pyridine is vigorously mixed with 1.96 g (0.01 mol) of gluconic acid and heated under nitrogen for 30 minutes to 140 C. The melt is cooled, triturated with a small amount of 50% ethanol and filtered. Wash with a small amount of cold ethanol and dry in vacuum at 50 ° C.
The yield of 4.1 g, so pl. 116-123 C.
Example 3. 3.043 g (0.01 mol) of 2-amino-3-ethoxycarbonyl mino-6- (p-fluorobenzylamino) -pyridine is suspended in 10 ml of absolute ethanol under nitrogen atmosphere, after which the resulting suspension is mixed with that prepared at 40 ° C within 40 min
benzylamino) -pyridine formula
BN-C-O-CgNs
AND
Shg O
CeHijOT
five
0
five
0
five
0
50
five
a solution of 1.781 g (0.01 mol) O-lactone of gluconic acid in 10 ml of water. The reaction mixture is heated for 45 minutes at 50 ° C until a clear solution is formed, after which the mixture is evaporated to dryness in vacuum at 40 ° C. The resulting residue is further evaporated with 10 ml of absolute ethanol and the product is dried in vacuum at 50 ° C.
Yield 4.33g.
Example 4. 3, 043 g (0.01 mol) of 2-amino-3-ethoxycarbonylamino-6- (p-fluoroben: 3ylamino) -pyridine is suspended in 10 ml of absolute ethanol under nitrogen atmosphere, after which the resulting suspension is smeared with the prepared at 80 ° C for 30 min with a solution of 1.781 g (0.01 mol) of C5-lactone gluconic acid in 1 O ml of water. The reaction mixture is heated at 90 ° C for 10 minutes to form a clear solution, after which the mixture is evaporated, dried under vacuum at 60 ° C. The resulting residue is further evaporated with 10 ml of absolute ethanol and the product is dried under vacuum at 50 ° C
Output 4.33 g.
The analgesic effect of flupirtine gluconate and flupirtine hydrochloride administered intravenously on the pain of dental pulp in awake dogs.
On a model of dental pulp of awake heterogeneous dogs, fpupyrtine gluconate and flupirtine hydrochloride are examined for their central analgesic effect after intravenous administration. The pain of dental pulp is caused by irritation with electricity. Already 15 minutes after intravenous administration, flupirtine shows a distinct, depending on dose, anesthetic effect. 30 min after intravenous administration, flupirtine gluconate with 0.72 mg / kg (w / base) is as strongly active as flupirtine hydrochloride with an EDgjj 0.69 mg / kg (calculated as base) . In the case of salts of both forms
СН2-1Щ
characterized in that with glucono2-aminr-3-ethoxycarbonylamino-6- (p-acid in a mixture, fluorobenzylamino) -pyridine with or with a CO-lactone glucono-2-amino-3-pyridine is fed at 40-90 s. interaction with gluconic acid
Flupirtin1Sh-S-0-C2H5
1Shg about
SBN
choo
500
3000
(Rig.1
Table continuation
2500 „2000 woo, 1500
bojiHOdof body, cn
1600 1 fOO1200 iOOOBOO600liOO200
4uc / fo, c / i
Fy

权利要求:
Claims (2)
[1]
Claim
The method of producing 2-amino-3-ethoxycarbonylamino-6— (p-fluorobenzylamino) - pyridinedluconate of the formula o-c _{g 5} • SBN _and O characterized in that
[2]
2-amino-3-ethoxycarbonylamino-6- (p ~ fluorobenzylamino) pyridine is reacted with gluconic acid
25 at 140 ^σ 0 or with O'-lactone of gluconic acid in a solvent-water mixture at 40-90 ° С.
Substance Dose, mg / kg (base) Number of animals Activity,% in relation to control animals  fifteen' thirty' 60 ' 90 ' 120 * Flupirtin gluconate 0.44 3 X -11, 8 -7.9 6.1 -10.8 -13.5 + SD 23.9 14.1 4.6 7.6 3.2 0.68 3 X 54,2 76.6 45.9 38,4 52.8 + SD 46.6 53,4 31,4 42.5 37.8 0.89 3 X 64,4 48.3 71.6 67.7 62,4 + SD 49.4 26.0 51, 6 59.3 57.1 eleveneleveneleven1 w 11 Q 1ι ω ιeleven 0.73 0.72 0.70 0.76 0.73 n.a. ♦ Flupirtine 0.22 3 X 17.7 23.3 34.3 14.8 27.7 hydrochloride. + SD 10,2 17,2 11, 6 12.1 16.3
Table continuation
K ---- ηSubstance Dose, Quantity Activity,% in relation to control animals mg / kg state (based on stomach-fifteen* thirty* 60 * 90 * 120 * waning) ny - ———- • --------——------ - 0.44 3 X 25.3 34,4 19.6 21.0 27.4 + SD 11, 9 16.7 18.2 10.9 17.3 0.89 3 X 40.3 58.3 72.5 43.6 40.3 + sd 9.8 16,2 . ’1.3 17.4 14.3 0.78 0.66
n h.
| Note, n.a. - insignificant, x - average value, SD - standard deviation.
FIG. 2
Forgiven

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引用文献:

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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DE19843416609|DE3416609A1|1984-05-05|1984-05-05|2-AMINO-3-ETHOXYCARBONYLAMINO-6-- PYRIDINE GLUCONATE AND PHARMACEUTICAL PREPARATIONS THAT CONTAIN THIS SUBSTANCE|

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