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US 4,536,508 AGranted
Triazoleamine derivatives having histamine H.sub.2 -antagonist properties
AssigneeGlaxo Group Limited
InventorsJohn W. Clitherow, Barry J. Price, John Bradshaw, Michael Martin-Smith, John W. M. Mackinnon, Duncan B. Judd, Roger Hayes
Life of this patent
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Abstract
The invention relates to compounds of the general formula (I) ##STR1## and physiologically acceptable salts, hydrates and bioprecursors thereof, which show pharmacological activity as selective histamine H.sub.2 -antagonists.
Claims25
Compounds of the general formula (I) ##STR24## and physiologically acceptable salts, hydrates;
- and tautomers thereof, in which
- R.sub.1 and R.sub.2, which may be the same or different, each represent hydrogen, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-6 alkenyl, aralkyl in which the alkyl moiety contains 1 to 6 carbon atoms;
- trifluoro C.sub.1-6 alkyl, or C.sub.1-6 alkyl substituted by hydroxy, C.sub.1-6 alkoxy, amino, C.sub.1-6 alkylamino or di C.sub.1-6 alkylamino or R.sub.1 and R.sub.2 may together with the nitrogen atom to which they are attached form a heterocyclic ring which is pyrrolidine, piperidine optionally substituted in the 4-position by C.sub.1-3 alkyl or hydroxy;
- tetrahydropyridine, morpholine, 2,6-di C.sub.1-6 alkylmorpholine, hexamethyleneimine or heptamethylenimine;
- Alk represents a straight or branched alkylene chain of 1 to 6 carbon atoms;
- Q represents a furan or thiophene ring in which incorporation into the rest of the molecule is through bonds at the 2- and 5-positions, the furan ring optionally bearing a further substituent R.sub.6 adjacent to the group R.sub.1 R.sub.2 N--Alk--, or Q represents a benzene ring in which incorporation into the rest of the molecule is through bonds at the 1- and 3- or 1- and 4-positions;
- R.sub.6 represents halogen or C.sub.1-4 alkyl which may be substituted by hydroxy or C.sub.1-4 alkoxy;
- X represents --CH.sub.2 --, --O--, --S-- or ##STR25## where R.sub.5 represents hydrogen or methyl;
- n represents zero, 1 or 2;
- m represents 2, 3 or 4;
- R.sub.3 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, ar C.sub.1-6 alkyl, hydroxy C.sub.2-6 alkyl, C.sub.1-6 alkoxy C.sub.1-6 alkyl or phenyl optionally substituted by one or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms;
- and
- R.sub.4 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, phenyl optionally substituted by one or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms;
- aralkyl in which the alkyl moiety contains 1 to 6 carbon atoms;
- hydroxy C.sub.1-6 alkyl, acyloxy C.sub.1-6 alkyl in which the acyl portion is C.sub.1-6 alkanoyl, benzoyl optionally substituted by 1 or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms, or aralkanoyl in which the alkyl moiety contains 1 to 6 carbon atoms;
- C.sub.1-6 alkoxy C.sub.1-6 alkyl, aryloxy C.sub.1-6 alkyl, ar C.sub.1-6 alkyloxy C.sub.1-6 alkyl;
- amino C.sub.1-6 alkyl, C.sub.1-6 alkyl-amino C.sub.1-6 alkyl, di C.sub.1-6 alkylamino C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkoxy, C.sub.1-6 alkythio or halogen and wherein aryl or as a group or part of a group is phenyl optionally substituted by one or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms.
14 more elements
Compounds of the general formula (I) ##STR26## and physiologically acceptable salts, hydrates;
- and tautomers thereof, in which
- R.sub.1 and R.sub.2, which may be the same or different, each represent hydrogen, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-6 alkenyl, ar C.sub.1-6 alkyl;
- trifluoro C.sub.1-6 alkyl, or C.sub.1-6 alkyl substituted by hydroxy, C.sub.1-6 alkoxy, amino, C.sub.1-6 alkylamino or di C.sub.1-6 alkylamino or R.sub.1 and R.sub.2 may together with the nitrogen atom to which they are attached form a heterocyclic ring which is pyrrolidine, piperidine optionally substituted in the 4-position by C.sub.1-3 alkyl or hydroxy;
- tetrahydropyridine, morpholine, 2,6-dialkylmorpholine, hexamethyleneimine or heptamethylenimine;
- Alk represents a straight or branched alkylene chain of 1 to 6 carbon atoms;
- Q represents a furan or thiophene ring in which incorporation into the rest of the molecule is through bonds at the 2- and 5-positions, the furan ring optionally bearing a further substituent R.sub.6 adjacent to the group R.sub.1 R.sub.2 N--Alk--, or Q represents a benzene ring in which incorporation into the rest of the molecule is through bonds at the 1- and 3- or 1- and 4-positions;
- R.sup.6 represents halogen or C.sub.1-4 alkyl which may be substituted by hydroxy or C.sub.1-4 alkoxy;
- X represents --CH.sub.2 --, --O--, --S-- or ##STR27## where R.sub.5 represents hydrogen or methyl;
- n represents zero, 1 or 2;
- m represents 2, 3 or 4;
- R.sub.3 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, ar C.sub.1-6 alkyl;
- hydroxy C.sub.2-6 alkyl, C.sub.1-6 alkoxy C.sub.1-6 alkyl or phenyl optionally substituted by one or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms;
- and
- R.sub.4 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, phenyl optionally substituted by one or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms;
- ar C.sub.1-6 alkyl, hydroxy C.sub.1-6 alkyl, C.sub.1-6 alkoxy C.sub.1-6 alkyl, aryloxy C.sub.1-6 alkyl, amino C.sub.1-6 alkyl, C.sub.1-6 alkyl-amino C.sub.1-6 alkyl, di C.sub.1-6 alkylamino C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkoxy, or halogen;
- provided that when X represents an oxygen atom or --NR.sub.5 -- and when n is zero then Q represents benzene;
- and wherein aryl or ar as a group or part of a group is phenyl optionally substituted by one or more C.sub.1-3 alkyl or alkoxy groups or halogen atoms.
14 more elements
Compounds which are:
- 1-methyl-5-[[4-[3-(1-piperidinylmethyl)phenoxy]butyl]amino]-1H-1,2,4-triazo le-3-methanol,
- 1-methyl-5-[[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amino]-1H-1,2,4-triaz ole-3-methanol,
- 3-methoxy-methyl-1-methyl-5-[[4-[3-(1-piperidinylmethyl)phenoxy]butyl]amino ]-1H-1,2,4-triazole or their physiologically acceptable salts.
Compounds which are:
- 3-phenylmethyl-N-[3-[3-(dimethylaminomethyl)phenoxy]propyl]-1H-1,2,4-triazo le-5-amine
- 5-[4-[3-(1-piperidinylmethyl)phenoxy]butyl]amino-1H-1,2,4-triazole-3-methan ol,
- 3-phenylmethyl-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-1,2,4-triazo le-5-amine,
- 5-[[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amino]-1H-1,2,4-triazole-3-one , or their physiologically acceptable salts.
1 more element
5-[[2-[[[5-[(dimethylamino)methyl]-2-fur anyl]methyl]thio]ethyl]amino]-1-methyl-1H-1,2,4-triazole-3-methanol and physiologically acceptable salts thereof.
5-[[2-[[[5-[(dimethylamino)methyl]-4-m ethyl-2-furanyl]methyl]thio]ethyl]amino]amino]-1-methyl-1H-1,2,4-triazole-3 -methanol and physiologically acceptable salts thereof.
1-methyl-5-[[3-[3-[(dimethylamino)methyl]phenoxy]pr opyl]amino]-1H-1,2,4-triazole-3-methanol and physiologically acceptable salts thereof.
Dependencies are inferred from the claim text.