Method of preparing pyridine derivatives (its versions)

专利摘要:
The present invention relates to new compounds having anti-hypertensive effect, which compounds are of the formula wherein R1 is selected from the group consisting of -CH1, -C2H5, -CH2CH2OCH3, - CH2CH2OC2H5, and (CH2CH2O)2CH3, and R2 is selected from the group consisting of -C2H3, -CH(CH3)2, -C(CH3)3, -CH(CH1)C2H3, -CH2CH2OCH(CH3)2, -CH(CH3)CH2OCH3, C(CH3)2CH2OCH3, -CH2C=CH, and -CH2C(CH3)=CH2, whereby R' and R are not the same, R' is selected from the group consisting of chloro and methoxy, and R' is selected from the group consisting of chloro, methyl, and methoxy, process for the preparation of said compounds, and pharmaceutical preparations containing said compounds.
公开号:SU856380A3
申请号:SU792781817
申请日:1979-06-29
公开日:1981-08-15
发明作者:Бернхард Бернтссон Педер；Айк Ингемар Карлссон Стиг；Эрнульф Гаардер Ян；Рихард Люнг Бенгт
申请人:Аб. Хессле (Фирма)；
IPC主号:

专利说明:

The invention relates to a process for the preparation of new pyridine derivatives (its variants), which have valuable pharmacological properties and can be used in medicine. A known method for producing pyridine derivatives from (-dicarbonyl compounds and ft-enaminocarboxylic compounds t. The purpose of the invention is to develop a method for producing pyridine derivatives that can be used in the pharmaceutical industry, based on a known method. where R is methyl, ethyl, methoxyztil, me.toxyethoxyethyl, ethoxyethyl, diethoxymethyl; l - ETHYL, isopropyl, tert-butyl, methylpropyl, methoxymethylethyl, isoproxyxyethyl, method xydimethylstil, ethoxyethyl, propargyl, methylallyl, and R and R do not have the same meaning; - chlorine, methoxy; - chlorine methyl, methoxy, the preparation of which implies that the compound of general form 3. and R have the indicated value. or R, interact with the compound of the general formula C; (where R has the meaning of the radical R, if R has the meaning of the radical R, or the value of the radical R, if R has the value of the radical n, and the target product is isolated or its other variant is that the compound of the indicated general formulas podverggiot reacted with a compound of general formula ° ° ,, HidOF wherein R has the meaning indicated for R, or I, in the presence of ammonia, n the desired product isolated. Example 1. 2.87 g of 2.3 dichlorobenzene 1-acetone acetic acetic acid methyl ester and 1.3 g of 3-aminocrotonic acid ethyl ester are dissolved in 10 mp of tertiary butanol. The reaction mixture is left at room temperature 8 for 4 days, after which the tertiary butanol is distilled off, the residue is dissolved and stirred with a small amount of isopropyl ether. At the same time, the target product is cris 1 tg. After recrystallization |} and from isopropyl ether, a pure 3-ester of methyl ester — 5-ester of 2,6-dimethyl-4- (2,3-dichlorophenyl) -1,4-dihydrospyridin-3, 5- dicarboxylic acid with so pl. 145C 75% yield of theory. Example 2. 5.74 g of 2,3-dichlorobenzylideneacetylacetic acid, methyl ester, 2.6 g of ethyl acetoacetate and 2.8 ml of concentrated ammonia are dissolved in 25 ml of tertiary butanol. The reaction mixture was left at room temperature for 5 days, after which the tertiary butanol was distilled off and the residue was dissolved in isopropyl ether. After the building has cooled, the target product is crystallized. After recrystallization from isopropyl ether, a semi-pure pure 3-methyl ester is a 5-complex ethyl ester of 2,6-dimethyl-4- (2,3-dichlorophenyl -1, 4-dihydropyridine-3, 5-dicarboxylic acid with m.p. .145 ° C. Yield of 59% of theory. Analogously to Examples 1.2, the compounds listed in Table 1 were obtained.Tabl 1. Biological tests: The antihypertensive effect of new compounds; The scientific research institutes are being studied for manifesting spontaneous hypertension. catheters are implanted into the abdominal aorta through the femoral artery. Median arterial blood flow The pressure and heart rate are continuously changed. After a two-hour period every 2 h control animals are given the test compound as a suspension in methocel {5 ml / kg body weight). In this case, doses are 1.5 and 25 µmol / kg body weight. Antihypertensive activity, i.e. the decrease in blood pressure after giving each dose is determined in percent of the initial control value of the coronary pressure and in relation to the dose embedded in the logarithmic scale. Then, the dose that reduces blood pressure by 20% is determined by interpolation. The results are summarized in table 2. table 2
40
oos
where R is methyl, ethyl, metroxyethyl, methoxyethoxyethyl, ethoxyethyl, diethoxymethyl; R is methyl, isopropyl, tert-butyl, methylpropyl, methoxymethyl ethyl, isopropyloxyethyl, -methoxymethyl methyl, ztokoiztil, propargyl, methylallyl, and R and R do not have the same value;
R
five
chlorine, methoxy; chlorine, methyl, methoxy,
characterized in that
compound of general formula 11
,AT
sg:

权利要求:
Claims (2)
[1]
K-J -., ... The specificity of smooth muscle relaxation is determined in the following way. An isolated rat portal vein and an isolated papilar heart muscle of the same rats are fed to the bath. The integrated compressive activity of the portal vein muscle and the maximum amplitude of the papillary heart muscle are measured. The corresponding activities for 30 min are taken as 100%, and the change in activity under the influence of the test compound is determined as a percentage of the activity for 30 minutes. The test compound is given every 10 minutes. At the same time, the activity in relation to vasodilatation {-log U of the portal vein) and in relation to the suppression of the activity of the cardiac muscle - papillary muscle) is determined by interpolation. The activity of each compound is determined by averaging the differences between the dB values obtained for dilating the vessels and suppressing the activity of the heart muscle. These logarithmic values are recalculated into simple numerical values, which are also listed in Table 2. A commercial product nifedipine — 3,5-complex dimethyl ester 2, b-dimethyl-4CH2-nitrophenyl -1, 4-dihydropyridine-3, 5-dicarboxylic acid is used as a comparison. Claims 1. Method for producing pyridine derivatives of general formula
. Where R and R- have the indicated values R has the meaning indicated
for R or R,
subjected to interaction with the compound of the General formula
 Hjm j
;: e-en-
Uz FROM
where R is the value of the radical R, if R has the value of the radical R, the value of the radical R, if R has the value of the radical R,
followed by the target
product.
[2]
2. The method of obtaining derivatives
pyridine total floscula I
dOOB
R is methyl, ethyl, methoxyethyl, methoxyethoxy ethyl, ethoxyethyl, diethoxymethyl; R is ethyl, isopropyl, tert-butyl, methylpropyl, methoxymethylethyl, isopropyloxyethyl, methoxymethyl methyl, ethoxyethyl, propargyl, methylallyl, and R and R do not have the same value;
OZ
; chlorine, methoxy; chlorine, methyl, methoxy, characterized in that the compound of general formula I
R and R have the indicated meanings; R has the meanings indicated for
Rfl or
subjected to the interaction of the formula IV
“H.
: tCHj 0y
/
where R has the meaning specified for R or R in the presence of ammonia, followed by isolation of the target product.
Sources of information taken into account when examining
1. Joel J., Smith G. Fundamentals of Chemistry of Heterocyclic Compounds. M., 1975, p.90.

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同族专利:

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公开号 | 公开日

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SE7807404L|1979-12-31|

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US4264611A|1981-04-28|

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NL930054I1|1993-09-01|

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AU529116B2|1983-05-26|

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LU88306I2|1994-05-04|

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NL940012I1|1994-08-01|

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US4264611B1|1984-07-17|

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IE48650B1|1985-04-03|

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NL930054I2|1994-02-16|

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HU178568B|1982-05-28|

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FI70573C|1986-09-24|

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CS241021B2|1986-03-13|

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NO1996006I1|1996-06-24|

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AT1237T|1982-07-15|

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SE429652B|1983-09-19|

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DK148978C|1986-08-18|

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SU915799A3|1982-03-23|

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JPS6121550B2|1986-05-27|

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BG61420B2|1997-07-31|

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CA1117530A|1982-02-02|

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FI792058A|1979-12-31|

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NO1994026I1|1994-12-21|

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DK275079A|1979-12-31|

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SG26085G|1986-01-24|

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DD144667A5|1980-10-29|

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HK60585A|1985-08-23|

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IE791217L|1979-12-30|

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DK148978B|1985-12-09|

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NO151965B|1985-04-01|

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NO792112L|1980-01-03|

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LU88666I2|1996-02-01|

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NZ190809A|1982-03-09|

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AU4831679A|1980-02-07|

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JPS559083A|1980-01-22|

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CY1299A|1985-10-18|

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EP0007293B1|1982-06-23|

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ZA792804B|1980-06-25|

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NO151965C|1985-07-10|

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DE2963150D1|1982-08-12|

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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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SE7807404A|SE429652B|1978-06-30|1978-06-30|2,6-dimethyl-4--1,4-dihydropyridine-3,5-dicarboxylic acid 3-methyl 5-ethyl ester|LV930698A| LV5473A3|1978-06-30|1993-06-28|Attempt to obtain pyridine derivatives|

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LTRP941A| LT2247B|1978-06-30|1993-09-06|PIRIDINE'S WORKSHOP BETWEEN / YOUR OPTIONS /|