Process for preparing derivatives of taurine

专利摘要:
Taurine derivatives with the chemical structure: (FORMULA) where R<u1>u = H; R<u2>u = a lower alkyl group with up to 4 carbon atoms or an acetyl group or where NR<u1>uR<u2>u = (FORMULA) These compounds were found in pharmacological studies to have qualities which make them useful as drugs.
公开号:SU1097198A3
申请号:SU823461553
申请日:1982-07-05
公开日:1984-06-07
发明作者:Хенрик Андерсен Ларс；Альбин Ингемар Лэйф
申请人:Медика Фармасьютикал Компани Лтд (Фирма)；
IPC主号:

专利说明:

midoethanesulfonyl chloride, 4.02 g of norm-propylamine hydrochloride, 120 ml of methylene chloride and -21 ml of a saturated solution of potassium carbonate. Recrystallization from 90% ethanol and ethyl acetate gives 4.87 g of suponfamide, m.p. 112-114 ° C. Calculated,%: C 52.7; H-5.4; N 9, 5 10.8, S3 045; Found,%: C 52.9; H 5.4; N 9.5 S 10.8, PRI me R 6. 2-phapimidoethanesulfonisopropylamide. 45 ml of methylene chloride and 2.48 g of isopropylamine are added to 21 ml of a saturated solution of potassium carbonate. 8.22 g of 2-phthalimidoethanesulfonyl chloride is dissolved in 45 ml of methylene chloride and the resulting solution is added to the reaction mixture. Recrystallization with ethanol gives 8.01 g of sulfonamide, mp. 137-139 ° C, yield 90% of theoretical. Calculated,%: C 52.7; H 5.4; N 9, S 10.8; C, j H, c. Found,%: C 53.0; H 5.5; N 9.5. 5 10.9. PRI me R 7. 2-Phthalimidoethansul background-nor-butylamide. 1.00 g of n-butylamine was added to a mixture of 2.40 g of phthalimidoethanesulfonyl chloride and 25 ml of methylene chloride and immediately thereafter, with stirring, 20 ml of 2.3 norms of sodium carbate solution. After that, the mixture is stirred for 10 minutes and the organic phase is separated, which is washed with water, dried and evaporated. During recrystallization from cyclohexane, 1.85 products are obtained, m.p. 71-73c. Yield 68% of theoretical. Calculated,%: C 54.2; H 5.8; N 9.0; S 10.3, C, 18 2 ° 4 S Found,%: C53.3; H5.8; N 9.1 S 10.3. PRI me R 8. 2-Phthalimidoethanesulfone-tert-butylamide. 36.1 g of 2-phthalimidoethanesulfonyl chloride in 98.2 ml of pyridine are cooled to 0-3 ° C. 4.8 g of tert-butylamine are added with stirring and the mixture is kept cold for 0.5 h, and then at room Tewnep for 2 h. The reaction mixture is poured into a mixture consisting of 300 g of ice, 70 MP of water and 130 ml of concentrated hydrochloric acid. The precipitate formed is filtered off, washed with water, dried and washed with ether. Recrystallization from ethyl acetate gives 27.5 g of sulfonamide, melting at 163-165 ° C. Yield 68% of theoretical. Calculated,%: C 54.2; H 5.8; N 9.0; 5 10.3, Cl4 "ie V Find,%: C 54.2; H 5.9; N 9.1; S 10.3. PRI me R 9. 2-Phthalimidoethanesulfonylpyridine. About half of the 6.48 g of 2-phthalimidoethanesulfonyl chloride was added to a mixture of 40 ml of ocetonitrile and 2.1 ml of pyrrolidine, while the temperature rose to 42 ° C. A further 2.1 ml of pyrrolidine is added and the temperature rises to 48 s. The remaining 2-phthalimidoethanesulfonyl chloride is added. When the reaction becomes slow, the mixture is boiled under reflux for 2.5 hours, after which it is cooled and filtered. Water is added and the precipitate is filtered off. When recrystallized from ethyl acetate, 2.97 g of amide are obtained, melting at 176-178 ° C. The yield is 39% of theoretical. Calculated,%: C 54.5; H 5.2; N 9.1; 5 10.4,. Found,%: C 54.4; H 5.2; N 9.1; 5 10.4. The anticonvulsant effect of the compounds has been studied in three types of experimental epilepsy. Convulsions are caused in mice with subcutaneous administration of pentylenetetrazol or strychnine or electrical stimulation with a current of 50 mA. Several compounds protect against convulsions in all three tests, both after oral and after intraperitoneal administration. The ED5 / dose effective for 50% of treated animals ranges from 103 mg / kg to 300 mg / kg (Table 1). Sedation is not observed. In table 1 antiepileptic creaking is presented.
Compound
Table 1
Anticonvulsant activity
mg / kg
ip
MET
STP
2-Phthalimidoethanesulfonamide
2-Phthalimido ethanesulfone-tert-Butnlamide
2-Phthalimidoethanesulfonylpyrrolide
2-Phthalimidoethanesulfonacetamide
2-Phthalimidoethanesulfonmethylamide
2-Phthalimidoethanesulfonylmethylamide
2-Phalimido ethanesulfone-nor-butylamide
2-Phthalimidoethanesulfonyl
2-Phthalimidoethanesulfonisopropylamide
2-Phalimido ethanesulfone-nor-propylamide Note. To study the antiarrhythmic effect of the compounds, an isolated perfused rat heart, prepared according to the Langendorff method, and an isolated spontaneously contracted atrium of the rat Arrhythmias caused by K deficiency and aknoinitis were used. A clear antiarrhythmic effect was shown (Tables 2 and 3. Some of the compounds have a better effect than the control compounds: lidocaine-2- (diethylamino) -M (2,6-dimethylphenyl acetamide, quinidine (b-methoxycinononan-9-6l and propanolol 1 - Isopropylamino-3- (1-naphthyloxy) 2-propanol. In addition to the tests described above, an MES test with a maximum electroshock test was used in METR, a MET test using D-pentylenetetrazole metra-el as a threshold convulsant. - strychnine in a living organism, i.e. about The tivoarrhythmic effect of the compounds is studied in guinea pigs with arrhythmias / induced by Ouabain. When new compounds are administered to the MopcKHM pigs, large doses of Ouabkin are required to cause arrhythmia (Table 4J. PropraMolol, which is used as a control compound in this test, causes Bradick Ardia, which the test subjects do not cause.Table 2 shows the effect of compounds on arrhythmia caused by K deficiency on the Langendorff-perfused heart of the rat.
2-Phthalimidoethanesulfon-nor-propylamide Table. 3 shows the ability of the tested compounds to provide protection against the development of arrhythmias in the controlled Quinidine
Propanolol
Lidocain
table 2
3 10
+10.3 secretly shrinking isolated. rat atria after administration of 2.5 10 M aconitine. T a b l and c a 3
Table 4 shows the ability of 60 test compounds to protect the continuation of Table 3.
development of arrhythmias in guinea pigs after infusion of 20 mg / kg / min. The central nervous system was studied in mice. For the study of motor coordination, a rotating rod method was used. For all tested compounds, the dose at which 50% of animals are knocked down with rod-5 is always higher than the anti-convulsant DB gg (dose preventing convulsions in 50% of animals). Although a sedative effect cannot be observed in these tests, sleep is caused by young hexabariturate, longer in mice after administration of the tested compounds, which, as it was found, have an anticonvulsant effect. 2-Phthalimido ethane-5 sulfonyl acetamide, which has anti-arrhythmic, but not anti-convulsive action, does not prolong sleep time. The hot plate method does not detect any analgesic effect on mice. Test compounds have neither diuretic (diuretic effect on non-anesthetized rats, nor any effect on blood circulation in normal-pressure anesthetized urethane rats. It was found that the compounds are non-toxic: oral after injection of 2 g / kg .

权利要求:
Claims (1)
[1]
METHOD FOR PRODUCING PRODUCTION OF ₇ NEW TAURINES of the general formula where R ₁ is hydrogen;
R ₂ is methyl, ethyl, n-propyl, isopropyl, n-butyl or R ″, h R together with the nitrogen atom form a radical ό due to the fact that phthalimidoethanesulfonyl chloride undergo γ-interaction with an amine of the general formula where R _n and R ₂ - have the indicated meanings, or with pyrrolidone in an organic solvent medium at 0-50 ° C in the presence of a base.
SU ... 10971
CO>
1097193

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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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SE8004261A|SE434638B|1980-06-06|1980-06-06|NEW THERAPEUTIC WORLDFUL TAURIN DERIVATIVES AND THEIR PREPARATION|

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