RU97118364A - PHENOETHYLAMINE DERIVATIVES, possessing a high affinity for the 5-HT1A receptor, a method for their production, their use as a medicinal product and a pharmaceutical composition on their basis - Google Patents

Claims (15)

1. Derivatives of phenoxyethylamine of General formula I:

wherein Ar is phenyl substituted with one or more substituents;
R is a hydrocarbon radical containing from 1 to 10 carbon atoms selected from alkyl, alkenyl, straight-chained or branched alkynyl radicals, cycloalkyl, cycloalkylalkyl or alkylcycloalkyl radicals, monocyclic or polycyclic, saturated or unsaturated;
a pyridyl or isoquinolyl radical;
phenyl, possibly substituted by one or more substituents,
and their salts. 2. Compounds of general formula I according to claim 1, characterized in that the substituent or substituents that may have a phenyl radical, denoted as Ar, is selected from halogen, lower alkyl, lower alkoxy, cyano, nitro, C (O) radicals NR ¹ R ² , C (O) NHOR ³ , NHC (O) R ⁴ , NHC (O) NHR ⁵ , CH ₂ NHC (O) NHR ⁶ , CH ₂ OR ⁷ ,
CH ₂ NHC (O) R ⁸ , CO ₂ R ⁹ , NHCO ₂ R ¹⁰ , C (O) R ¹¹ , SR ¹² ; in which R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ means independently from each other a hydrogen atom or lower alkyl, and R ⁹ , R ¹⁰ , R ¹¹ , R ¹² means independently lower alkyl; and the substituent or substituents that the phenyl radical may have, denoted as R, are selected from lower alkyl, lower alkoxy, halogen, hydroxy, nitro, amino or acylamino radicals. 3. Compounds of general formula I according to claim 1 or 2, characterized in that Ar means a phenyl radical substituted by a substituent selected from hydroxy, methoxy, —C (O) NH methyl, —NHC (O) methyl, —NHCO ₂ R _'10 wherein R' ₁₀ represents a methyl or ethyl radical, -NHCONH _2, -C (O) NHOH, and R is cyclopentyl, cyclohexyl, cycloheptyl, cyclopentylmethyl, adamantyl, tert-butyl, neopentyl, phenyl, fluorophenyl. 4. Compounds of general formula I in PP.1-3, which are the following compounds: —N [4- {2- (2-methoxyphenoxy) ethyl} aminobutyl] benzamide; -N [4- {2- (2-methoxyphenoxy) ethyl} aminobutyl] adamantamide; -N [4- {2- (2-methylaminocarbonylphenoxy) ethyl} aminobutyl] benzamide; -N [4- {2- (2-hydroxyphenoxy) ethyl} aminobutyl] benzamide; -N [4- {2- (2-methoxyphenoxy) ethyl} aminobutyl] cyclohexylamide; -N [4- {2- (2-methoxyphenoxy) ethyl} aminobutyl] cycloheptylamine; -N [4- {2- (2-methoxyphenoxy) ethyl} aminobutyl] 2-bicyclo [2.2.1] heptylamine,
and salts of these compounds with inorganic or organic acids. 5. The method of obtaining compounds of General formula I, described in claim 1, characterized in that
a) either carry out the reaction of the compounds of formula II

in which Ar has the meaning given in paragraph 1, with a compound of formula III

in which X is halogen or pseudohalogen, to obtain the compounds of formula IV

which is subjected to the reaction of removal of phthalimido groups to obtain the compounds of formula V

which is treated with an acid derivative of RCO ₂ H as an acylating agent, in which R has the meaning given in paragraph 1 to obtain a product of formula VI

b) either carry out the reaction of the compounds of formula VII

with N-benzylethanolamine formula

to obtain the compounds of formula VIII

which is converted to a compound of formula IX

wherein Y is a halogen or pseudohalogen radical, the resulting compound of formula IX is converted to a compound of formula VI described above by reacting with a phenol derivative of formula ArOH, a compound of formula VI is converted to a compound of formula I by cleaving the benzyl function and, if desired, the compound of formula I converted into acidic salts by reaction with the corresponding acid.  6. The compounds of formula I according to claim 1, as well as their addition salts with pharmaceutically acceptable inorganic or organic acids as a medicine.  7. The compounds of formula I in claims 2 to 4, as well as their addition salts with pharmaceutically acceptable inorganic or organic acids as a medicine.  8. Pharmaceutical formulations containing as active principle at least one of the medicines specified in one of paragraphs 6 or 7.  9. The compounds of formula I according to any one of paragraphs.1 to 4, characterized in that they are used for the manufacture of antiemetic drugs.  10. The compounds of formula I according to any one of paragraphs.1 to 4, characterized in that they are used for the manufacture of medicines intended to reduce gastric secretion.  11. The compounds of formula I according to any one of paragraphs.1 to 4, characterized in that they are used for the manufacture of medicines designed to accelerate the relaxation of the stomach.  12. The compounds of formula I according to any one of paragraphs.1 to 4, characterized in that they are used for the manufacture of medicines intended to accelerate the passage through the intestines.  13. The compounds of formula I according to any one of paragraphs.1 to 4, characterized in that they are used for the manufacture of medicines intended for the treatment of anxiety, depression, sleep disorders.  14. The compounds of formula I according to any one of paragraphs.1 to 4, characterized in that they are used for the manufacture of medicines intended for the treatment of cardiovascular diseases, in particular hypertension.  15. As new industrial products of the compound of formulas IV, V, VI, VIII and IX, defined in paragraph 5.