Aminotetralols
AssigneeTakeda Chemical Industries, Ltd.
InventorsHirosada Sugihara, Masazumi Watanabe, Michio Motohashi, Masao Nishikawa, Yasushi Sanno
Life of this patent
Estimating the term…
Abstract
Novel aminotetralol compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, acyl derived from carboxylic acid, or a hydrocarbon group which may be substituted; --OZ.sup.1 is hydroxyl which may be protected; Y is hydrogen, acyl, hydroxyl which may be protected, amino which may be substituted, nitro, cyano or halogen; and n is zero, 1 or 2 with a proviso that when Y is hydrogen or hydroxyl which may be protected, n is not zero, and their salts, have excellent pharmacological activities such as strong bronchodilating activity. They are useful as medicines, for example, for treatment of asthma.
Claims49
A compound selected from the group consisting of compounds of the formula ##STR60## wherein R.sup.1 is (1) hydrogen, (2) alkyl of up to 6 carbon atoms, (3) alkenyl of up to 6 carbon atoms, (4) alkynyl of up to 6 carbon atoms,
- said alkyl, alkenyl and alkynyl groups being unsubstituted or substituted by at least one of (a) cycloalkyl of 3-7 carbon atoms, (b) cycloalkenyl of 3-7 carbon atoms, (c) cycloalkylidene of 3-6 carbon atoms, (d) phenyl, (e) naphthyl, (f) hydroxyl, (g) alkoxy of 1-4 carbon atoms, (h) phenoxy, (i) naphthoxy, (j) halogen, (k) acetyl, (l) propionyl, (m) butyryl, (n) benzoyl, (o) unsubstituted amino and (p) nitro,
- said cycloalkyl, cycloalkenyl, phenyl and naphthyl groups being unsubstituted or substituted by at least one of (a) alkyl of 1-4 carbon atoms, (b) hydroxyl, (c) alkoxy of 1-4 carbon atoms and (d) halogen, (5) cycloalkyl of 3-7 carbon atoms, (6) cycloalkenyl of 3-7 carbon atoms, (7) phenyl, or (8) naphthyl,
- said last referred to cycloalkyl, cycloalkenyl, phenyl and naphthyl groups being unsubstituted or substituted by at least one of (a) alkyl of 1-4 carbon atoms, (b) hydroxyl, (c) alkoxy of 1-4 carbon atoms and (d) halogen,
- Oz.sup.1 is unprotected hydroxyl or protected hydroxyl,
- Y is (1) hydrogen, (2) unprotected hydroxyl, (3) protected hydroxyl, (4)unsubstituted amino, (5) monoalkylamino of not more than 3 carbon atoms, (6) dialkylamino of not more than 3 carbon atoms in each alkyl group, (7) nitro or (8) halogen,
- n is zero, 1 or 2, with the proviso that when Y is hydrogen, uprotected hydroxyl or protected hydroxyl n is 1 or 2,
- and physiologically acceptable salts thereof.
Trans-2-cyclobutylamino-1,6-dihydroxy-5-hydrox ymethyl-1,2,3,4-tetrahydronaphthalene.
Trans-5-amino-2-cyclobutylamino-1, 6-dihydroxy-1,2,3,4-tetrahydronaphthalene.
Trans-2-cyclobutylamino-1,6-dihydroxy- 5-methylamino-1,2,3,4-tetrahydronaphthalene.
Trans-1,6-dihydroxy-5-hydroxymethyl-2-is opropylamino-1,2,3,4-tetrahydronaphthalene.
Trans-5-amino-1,6-dihydroxy-2-isopropyl amino-1,2,3,4-tetrahydronaphthalene.
Trans-1,6-dihydroxy-2-isopropyla mino-5-methylamino-1,2,3,4-tetrahydronaphthalene.
Trans-2-tert-butylamino-1,6-dihydroxy-5-hydro xymethyl-1,2,3,4-tetrahydronaphthalene.
5-amino-2-tert-butylamino-1,6-dihydroxy-1,2,3,4-tetrahydronaphthalene.
Trans-2-tert-butylamino-1,6-dihydroxy-5-methylamino-1,2,3,4-tetrahydron aphthalene.
Trans-1 ,6-dihydroxy-5-hydroxymethyl-2-(.alpha.-methyl-p-hydroxyphenethylamino)-1,2 ,3,4-tetrahydronaphthalene.
5-amino-1,6-dihydroxy-2 -(.alpha.-methyl-p-hydroxyphenethylamino)-1,2,3,4-tetrahydronaphthalene.
Trans-1,6-dihydroxy-5-hydroxymethyl-2-(.alpha.-methyl-p-methoxyphenethy lamino)-1,2,3,4-tetrahydronaphthalene.
Trans-5-amino-1,6-dihydroxy-2-(.al pha.-methyl-p-methoxyphenethylamino)-1,2,3,4-tetrahydronaphthalene.
Trans-1,6-dihydroxy-5-methylamino-2-(.alpha.-methyl-p-methoxyph enethylamino)-1,2,3,4-tetrahydronaphthalene.
Trans-2-cyclopentylamino-1,6-dihydroxy-5 -hydroxymethyl-1,2,3,4-tetrahydronaphthalene.
Trans-5-ethylamino-1,6-dihydroxy-2-isopro pylamino-1,2,3,4tetrahydronaphthalene.
A compound selected from the group consisting of compounds of the formula ##STR61## wherein R.sup.1 is alkyl of up to 6 carbon atoms, said alkyl being unsubstituted or substituted by phenyl, said phenyl being unsubstituted or substituted by hydroxyl or alkoxy of 1-4 carbon atoms, or R.sup.1 is cycloalkyl of 3-7 carbon atoms,
- Oz.sup.1 is unprotected hydroxyl,
- Y is unprotected hydroxyl, unsubstituted amino or monoalkylamino of not more than 3 carbon atoms,
- n is zero when Y is unsubstituted amino or monoalkylamino of not more than 3 carbon atoms, and n is 1 when Y is unprotected hydroxyl,
- and physiologically acceptable salts thereof.
A pharmaceutical composition which comprises
- A. as active ingredient, at least one compound selected from the group consisting of compounds of the formula ##STR62## wherein R.sup.1 is (1) hydrogen, (2) alkyl of up to 6 carbon atoms, (3) alkenyl of up to 6 carbon atoms, (4) alkynyl of up to 6 carbon atoms,
- said alkyl, alkenyl and alkynyl groups being unsubstituted or substituted by at least one of (a) cycloalkyl of 3-7 carbon atoms, (b) cycloalkenyl of 3-7 carbon atoms, (c) cycloalkylidene of 3-6 carbon atoms, (d) phenyl, (e) naphthyl, (f) hydroxyl, (g) alkoxy of 1-4 carbon atoms, (h) phenoxy, (i) naphthoxy, (j) halogen, (k) acetyl, (l) propionyl, (m) butyryl, (n) benzoyl, (o) unsubstituted amino and (p) nitro,
- said cycloalkyl, cycloalkenyl, phenyl and naphthyl groups being unsubstituted or substituted by at least one of (a) alkyl of 1-4 carbon atoms, (b) hydroxyl, (c) alkoxy of 1-4 carbon atoms and (d) halogen, (5) cycloalkyl of 3-7 carbon atoms, (6) cycloalkenyl of 3-7 carbon atoms, (7) phenyl, or (8) naphthyl,
- said last referred to cycloalkyl, cycloalkenyl, phenyl and naphthyl groups being unsubstituted or substituted by at least one of (a) alkyl of 1-4 carbon atoms, (b) hydroxyl, (c) alkoxy of 1-4 carbon atoms and (d) halogen,
- Oz.sup.1 is unprotected hydroxyl or protected hydroxyl,
- Y is (1) hydrogen, (2) unprotected hydroxyl, (3) protected hydroxyl, (4) unsubstituted amino, (5) monoalkylamino of not more than 3 carbon atoms, (6) dialkylamino of not more than 3 carbon atoms in each alkyl group, (7) nitro or (8) halogen,
- n is zero, 1 or 2, with the proviso that when Y is hydrogen, unprotected hydroxyl or protected hydroxyl n is 1 or 2,
- and physiologically acceptable salts thereof, and
- B. a pharmaceutically acceptable carrier therefor.
A pharmaceutical composition which comprises
- A. as active ingredient, at least one compound selected from the group consisting of compounds of the formula ##STR63## wherein R.sup.1 is alkyl of up to 6 carbon atoms, said alkyl being unsubstituted or substituted by phenyl, said phenyl being unsubstituted or substituted by hydroxyl or alkoxy of 1-4 carbon atoms, or R.sup.1 is cycloalkyl of 3-7 carbon atoms,
- Oz.sup.1 is unprotected hydroxyl,
- Y is unprotected hydroxyl, unsubstituted amino or monoalkylamino of not more than 3 carbon atoms,
- n is zero when Y is unsubstituted amino or monoalkylamino of not more than 3 carbon atoms, and n is 1 when Y is unprotected hydroxyl,
- and physiologically acceptable salts thereof, and
- B. a pharmaceutically acceptable carrier therefor.
Dependencies are inferred from the claim text.