4-amino-tetrahydro-2-naphthoic acid derivatives

Details 4-amino-tetrahydro-2-naphthoic acid derivatives 4-amino-tetrahydro-2-naphthoic acid derivatives

1984-05-07

1986-07-01

Trousof, Natalie

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

514567, 514619, 560 47, 562456, 564163, A61K 31215, A61K 31195, A61K 31165, C07C10322

Patent

active

045980934

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD AND DISCLOSURE OF INVENTION

This invention relates to novel and therapeutically useful 4-amino-1,2,3,4-tetrahydro-2-naphthoic acid derivatives of the formula: ##STR2## and salts thereof, wherein X is halogen atom, i.e. fluorine, chlorine, bromine or iodine; n is 1 or 2; R.sup.1 is hydroxy group, lower alkoxy group, e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, etc. or amino group; and R.sup.2 is hydrogen atom, lowr alkanoyl group, e.g. acetyl, propionyl, isopropionyl, butyryl, isobutyryl, etc. or carbamoyl group.
Japanese Patent Publication No. 43-22097 (1968), Chem. Pharm. Bull., 14, 324 (1966) and J. Med. Chem., 21, 1105 (1978) make mention of compounds useful as an intermediate for the synthesis of a certain kind of analgesics, which compounds are represented by the formula: ##STR3## wherein X' is hydrogen atom or methoxy group, R.sup.1 ' is hydroxy group or lower alkoxy group, and R.sup.2 ' is hydrogen or lower alkanoyl group.
The present inventors have synthesized a variety of the derivatives having gamma-aminobutyric acid (hereinafter abbreviated as GABA) moiety in their structure and investigated into their usefullness. As a result, this invention has been accomplished on the basis of the new finding that the compounds of the invention unexpectedly have potent diuretic and blood pressure lowering actions, although they show little protecting effects on the functions in which only the central nervous system participates such as convulsions or fatal convulsions induced by a GABA antagonist such as bicuculline or picrotoxin.
To the contrary, with the aforementioned known comounds these actions are extremely weak or are not substantially apparent.
The compounds of formula (I) wherein R.sup.2 is hydrogen can be produced for example by the following Methods 1 to 3:


Method 1

Method of reducing an oxime compound of the formula: ##STR4## wherein X, n and R.sup.1 are the same as defined above. Preferably, catalytic reduction is carried out in the presence of a metallic catalyst such as Raney nickel, platinum oxide or palladium carbon in an inert solvent, preferably a lower alkanol such as methanol, ethanol or the like or a lower alkanoic acid such as acetic acid, if desired in the presence of ammonia for prevention of possible polymerization, at a temperature of room temperature to 150.degree. C., preferably 50.degree. to 100.degree. C. under normal pressure or 50 to 150 atm of hydrogen. Here, hydrogen or hydrazine may be used as a hydrogen source. Otherwise, the reduction may be carried out by the use of metallic sodium in liquid ammonia containing methanol or by the use of both hydrochloric acid or acetic acid and zinc or tin.


Method 2

Method of subjecting a compound of the formula: ##STR5## to ammonolysis in water or lower alkanol, wherein X, n and R.sup.1 are the same as defined above, and Y is halogen atom, methylsulfonyloxy group, p-tolylsulfonyloxy group or a like reactive residue.


Method 3

Method of subjecting a compound of the formula: ##STR6## to Leukart reaction, wherein X, n and R.sup.1 are the same as defined above. That is, a compound of formula (IV) and urea, ammonium formate or the like undergo fusion reaction in the presence of formic acid at 150.degree.-200.degree. C. and the resulting product is hydrolyzed to give the intended compounds.
The compounds of formula (I) wherein R.sup.2 is hydrogen are allowed to react with a reactive derivative of lower alkanoic acid such as acid halide, acid anhydride or the like to give the compounds of formula (I) wherein R.sup.2 is lower alkanoyl group. They are allowed to react with potassium cyanate or sodium cyanate in an aqueous lower alkanol to give the compounds of formula (I) wherein R.sup.2 is carbamoyl.
The compounds of formula (I) wherein R.sup.1 is hydroxy group are allowed to esterify with a lower alkanol in the presence of mineral acid such as hydrochloric acid or sulfuric acid to give the compounds of formula (I) wherein R.sup.1 is lower alkoxy. The ester compounds thus obtained or their free carboxyli

REFERENCES:
patent: 3953506 (1976-04-01), Spicer et al.
patent: 3978124 (1976-08-01), Fried et al.
Lipschitz et al, J. Pharmacol. Exp. Therap., vol. 79, pp. 97-110 (1943).
Topliss, J. Med. Chem., vol. 20, No. 4, pp. 463-469, (1977).
Topliss, J. Med. Chem., vol. 15, No. 10, pp. 1006-1011, (1972).
Willard et al, Arch. Int. Pharmacodyn., vol. 173, pp. 11-15, (1968).
Loscher, Arch. Int. Pharmacodyn., vol. 257, pp. 32-58, (1982).
Kometani et al, J. Med. Chem., vol. 21, pp. 1105-1110, (1978).
Shiotani et al, Chemical and Pharmaceutical Bulletin, vol. 14, No. 4, pp. 324-329, 1966.

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