• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    New compounds of the formula …<CHEM>… or a pharmaceutically acceptable salt thereof, in which formula… R<1> form H, a straight or branched alkyl group containing 1-5 carbon atoms, a cycloalkyl group containing 3-6 carbon atoms, or a cycloalkylalkyl group containing 4-6 carbon atoms;… R<2> is H, Cl, Br or F;… n is 2, 3, or 4;… R<1><1> and R<1><2>, which are the same or different, are H, an alkyl group containing 1-4 carbon atoms, a hydroxyalkyl group containing 1-4 carbon atoms, an alkoxyalkyl group containing 2-4 carbon atoms in total, or R<1><1> and R<1><2> together with the adjacent nitrogen atom form a morpholino group, are described, as well as methods for their preparation, pharmaceutical preparations thereof and methods of treatment employing the same. The compounds are potent beta 1-selective adrenoceptor blockers having a degree of intrinsic activity.
    公开号:SU1169533A3
    申请号:SU833657075
    申请日:1983-10-31
    公开日:1985-07-23
    发明作者:Бениамин Рудольф Густавссон Билл；Андерс Хедберг Свен；Торстен Лундгрен Бо
    申请人:Актиеболагет Хессле (Фирма)；
    IPC主号:
    专利说明:

    The invention approaches the method of obtaining new derivatives. As with nopropanol, which have blocking / E-receptor activity and can be used in medicine. The aim of the invention is to obtain new: aNmHonpona ™ nol derivatives that exhibit heartbeat / S-adrenoblocking activity, Example. 35-3 g N 12 - {(2-OCI-3-C - (2-methoxyethoxy) phenoxy} propylamino J ethyl j urea and 2-6 g of 2- (2 hydroxy ethoxy) ethanol dimesylate are added to a solution of 500 mp of la and O, 5 g of sodium. The solution is first stirred at room temperature for 3 hours and then heated to reflux for 24 hours followed by evaporation, the residue is distributed between water and chloride and methylene. The organic phase is dried over sodium sulfate, filtered and concentrated. The residue is crystallized from ethyl acetate and simple ether to give (2 methoxyethoxy) phenoxy jiip pilamino J jaTmi y-4 - morpholine-carboxamide with m, pl. (base). The following compounds are obtained in a similar way: m {-2-C2 Oxy-3- 4- (2-ethoxy ethoxy) phenyl-1-propyl-1L-j-ethyl-4-mor folincarboxamide. i,: l, Ij-lT d (about novaniya). N- {2- 2 Oxy-3- 4- (2-tion of cycl-methoxyethioxy) phenoxy-propylamino ethyl 1-4-morpholium carboxes ID. T. pl. 80-81 0 (base). M- {2-C2-Oxy-3- 4 (2 cy1shobutyl methoxyethoxy) phenoxy | -propylami- "-h but JJsTtra j-4-morpholine-carbox m D. T. pl, 91-93 C (base). 2-OXY - 3- 4- (2-methyl1 ropi xi) ethoxyphenyl pronylamino1-methyl j-4-morpholinecarboxam 1 To T, mp, 9596 ° С (base), Y- {2 -2-Oxy 3- 4- (2 -propoxyethoxy) phenoxy pronylamino ethyl ethyl-4-morpholic carboxamide. T, pl. 88C (base). N- {2 C2-Oxy-3- 4- (2- (2, 2 - dimethyl-propoxy) ethoxy) -phenoxy (-propylamide i.oh1 J-4-morpholin-carboxamide, T. pl. (Base). C2-OXY - 3-2-bromo-4-C2-this sioethoxy) phenoxy2 propylamino jJaTHii in 4-morpholine-carboxamide, T, mp, 98 C. Biological activity of new compounds. Example 1. The activity of new compounds on cardiac and vascular / -adrenoceptors was studied as follows. 16 hours prior to anesthesia, cats (males and females) were given intramuscularly reserpine in an amount of 5 mg / kg body weight. Cats were anesthetized with pentobarbital sodium in an amount of 30 mg / kg body weight and artificially ventilated through the tracheal cannula. Both vagal nerves cut the heart rate recorded by OBOHH- by ocIll lm of blood pressure. A cannula was inserted into the femoral artery of one posterior leg. Selected blood was pumped into the distal part of the artery in a constant quality. Perfusion pressure measured; Chips, with changes indicating a change in peripheral vascular resistance. The intravenous dose of prekalin, which resulted in an increase in the heart rate of approximately 80% of the maximum effect of isoprenaline, was determined. This dose of isoprenaline was followed by dilation of the vessels in the hind leg, which was also equal to approximately 80% of the maximum response. After receiving; none of the control reactions, the experiments were conducted in cycles of 30 minutes. Each cycle was started by internal infusion of the test of the compounds, for 10 minutes; iin, Itypea 10 min after the end of the injection of the test compounds was given isoprenaline. For each dose of the test compound, the maximum decrease in the heart rate (ES) caused by isoprenaline and the perfusion pressure (, S1) were determined as a percentage blockade according to the formula: Reduction of the reaction caused by isoprenaline, „„ (ES: beating / min, DP: mm Hg .st.) iOOx Isoprenaline control reaction (ES: beat / min, DG1: mmHg) Minimum dose of the test compounds is 0.05 µmol / kg. This dose was increased by a factor of 4 in the hyede of uHKJ.iii. According to the percentage blockade of the heart rate and the perfusion pressure and the log dose of the test compounds, the dose was determined to characterize the blocking activity of the new compounds, Example 2. Sympathicimetic activity of the new The compounds were determined on cats (males and females), which, 16 hours prior to anesthesia with pentobarbital sodium (30 mg / kg), were given intraperitoneally reserpine in an amount of 5 mg / kg. In this case, the vagus nerve was cut. Heart beat frequency was recorded by oscillation of blood pressure through a carotid arterial catheter. After determining the maximum frequency of heartbeats caused by isoprenamine, the test compounds were slowly intravenously injected (for 2 minutes) every 12 minutes in increasing doses. The heart rate of beats was recorded 5 min after giving each dose of the test compound until the heart rate stopped. The maximum response to isoprenamine was then redetermined and the sympathicometric activity of the test compounds was determined as the percentage of the maximum effect of the isoprene amine according to the formula: Maximum effect of the test compound (beats / min) Maximum action of isoprenamine after giving the compound to be tested (beats / min). In Examples 1 and 2, the following activity of the compounds studied was detected. For the blocking D-adrenoceptor activity (ES), the ED dose of the studied compounds (example and Nr.I-VII) was 0.03-1.2 µmol / kg, and for the blocking () 2) renal activity receptor (DP), the dose of ED. these compounds ranged from 12 to 50 µmol / kg. At the same time, the EDU DPgED ES ratio was approximately 50-1000. The sympatomic activity of these compounds, defined as a positive chronotropic effect, was 15-35% of the maximum increase in heart rate. The known apylaminopropanol derivatives showed 25-40% less v-adrenoceptor blocking activity and 20-30% less sympathicomimetic activity.
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING AMINOPROPANOL DERIVATIVES of the General Formula
    OH about
    I P / - oc-HjC ^ ocHaR., Where R ^ is a hydrogen atom, C ^ -C ^ -alkyl or C e -C 4 -cycloalkyl, R 2 is a hydrogen or bromine atom, characterized in that the compound of the general formula
    HE ' " . '·
    QCVljtHCWjNUCUjCHiMWCQNHtCUi ^ lOtCMj ^ SOjCMj (έ ! AcHiCMjOCUjk, wherein R 3 and R 2 have the abovementioned meaning, are cyclized in a solvent in the presence of a base at the reflux temperature of the reaction mixture, followed by isolation of the expected product..
    SU, "1169533
    3>
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    法律状态:
    优先权:
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