Method of preparing amino-derivatives of propandiol or their pharmacetically adopted salts with acid

专利摘要:

公开号:SU850005A3
申请号:SU792807156
申请日:1979-08-31
公开日:1981-07-23
发明作者:Ричард Краска Аллен
申请人:Пфайзер Инк (Фирма)；
IPC主号:

专利说明:

am, methanesulfonate, lactate and suraine salts.
Preferred salts are base hydrochlorides.
Particularly valuable are the following compounds and their pharmaceutically acceptable salts: 1-G2,3-di (n-octadecyloxy-) propyl-4-aminomethyl-4-feH11ppiperidine; 1-C2, 3-di (n-hexadecyloxy) propyl-4-aminomethyl-4-phenylpiperidine and 1-C2,3-di-t-tetra-d-cycloxy) propyl-4-aminomethyl-4-phenylpiperidine.
The compounds of general formula 1 possess antiviral activity, which is determined using two independent techniques. In accordance with the first, the test compound was intraperitoneally administered to mice 18-24 hours before contacting them with a lethal dose of encephalomyocarditis virus (EHR). After contacting, survival data is determined and compared with data for animals that have not been protected.
In accordance with the second method, a monolayer of human cells of nasal polyps grown on microtiter plates is treated with the test compound approximately 18 hours before the treatment with an lethal dose of vesicular stomatitis virus (PBS). The test compound is washed from monolayers prior to treatment with the virus. Extracted culture medium from the plates after the incubation period after infection is titrated to the amount of infectious virus present in the microtiter plates of mouse (L-929) fibroblasts. The comparison is carried out with the virus yield data for the culture medium extracted from unprotected polyp cells.
In addition, for the synthesized compounds, their ability to enhance the known antiviral activity of polyinosinic (polycytidylic) acid is determined. Some of the compounds are tested for their ability to induce the production of circulating interferon in mice after parenteral administration.
Parenteral, topical, or intranasal use of the described amines for mammals prior to contact of mammals with an infectious virus provides for rapid formation of resistance to the virus. Consumption should be made 2-1 days before contact with the virus, although this value varies somewhat depending on the specific animal species and the specific infectious virus.
Example 1. 1- (2,3-di (n-hexadecyloxy) propyl 3-aminomethyl-4-phenylpiperidine dihydrochloride. A., 3- (n-hexadecyloxy) propanol II-4-diano-4-phenylpiperidine.
A mixture of 1,2-di-O- (n-hexadecyl) -3-0 (p-tosyl) -glycerin (6.96 g, 10 mmol), 4-cyano-4-phenylpiperidine hydrochloride (1.13 g, 10 mmol), triethylamine (2 ml), and N, N-dimethylformamide (40 ml) are stirred for 16 hours at 95-100 ° C. The reaction mixture is cooled, diluted with water (200 ml) and extracted with ethyl acetate (Sx -150 ml) . The combined ethyl acetate extract was dried (MgSO4), filtered and evaporated in vacuo to an oil (6 g), which was purified by column chromatography (elution with a mixture of benzene / ethyl acetate). (oil, IR spectrum (СНСе ,,) 2220 cm).
.B. The solution, 3-di (n-hexadecyloxy) ponyl-4-cyano-4-phenyl-piperidine (2.5 g, 3.6 mmol) in diethyl ether (100 ml) is treated with lithium-aluminum hydride (0.4 g, 10.5 mmol) and the resulting mixture is stirred for 4 hours at room temperature, then carefully treated with water (100 ml) and extracted with ether (3x lOO ml). The combined ether extract was dried (M9S04), filtered and evaporated in vacuo to an oil, which was purified by chromatography on silica gel (eluted with benzene / ethanol) and then dissolved in ether. The solution is treated with gaseous hydrogen chloride and then evaporated in vacuo to give a solid, which is recrystallized from ethyl acetate (1.1 g, a solid containing about 3/4 mol HdO per mole of the title product, 40% yield, mp. 132-134C.
Found,% g C 70.74, H 11.35, N 3.40.
Calculated% C 70.60, H 11.53, N 3.50.
Examples .2-4. Analogously to the procedure described in Example 1, the following compounds were prepared, starting from the corresponding 1,2-di-O- (n-alkyl or alkenyl) -3-0- (n-tosyl) glycerol.
The synthesized compounds of the general formula J or their pharmaceutically acceptable salts with acids can be used to combat viral infections of mammals. 2n-tetradecyl 3n-octadecyl 4n-octadecyl-9-enyl .. N 2Hse140-142 69,4611,253,7569,4511,003,45 С ,, 115-117 71,9511,603,2971,6711,193, 38 Yai U 118-120 71.1711.233.2571.0610.843.09

权利要求:
Claims (1)
[1]
Claim
A method of producing amino derivatives of propanediol of the general formula I l, o-en _g where R ₁ and 1 ^ each can be normal C _w ^ ₀ -alkyl or normal C. „-alkenyl not having a double bond in position k, or their pharmaceutically acceptable salts with acids, characterized in that the nitrile of the general formula II ,,.,. 30¾
20 I ₂ -0- <где where the values of HZ and R ^ are given as vian, are subjected to reduction with complex alkali metal hydride and the obtained target product is isolated in free form or in the form of a pharmaceutically acceptable salt.

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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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US05/825,535|US4166132A|1977-08-18|1977-08-18|Antiviral amine derivatives of glycerol and propanediols|

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