Aryloxypropanolamine .beta. 3 adrenergic agonists
AssigneeBristol-Myers Squibb Company
InventorsPhilip M. Sher, William N. Washburn, Kathleen M. Poss
Life of this patent
Estimating the term…
Abstract
Compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof wherein: R.sup.1 to R.sup.9 are as defined herein and m is the integer 0 or 1. These compounds are beta 3 adrenergic receptor agonists and are useful, therefore for example, in the treatment of diabetes, obesity, gastrointestinal diseases and achalasia.
Claims16
A compound of the formula ##STR44## or pharmaceutically acceptable salts thereof where R.sup.1 is hydrogen, hydroxy, alkoxy, nitro, amino, alkylsulfonylamino, acylamino, alkylsulfonyl, alkyl, cycloalkyl, phenyl, hydroxymethyl, cyano, aminocarbonyl, halogen or trifluoromethyl;
- R.sup.2 and R.sup.3 together with the carbon atoms to which they are attached, form a heterocycle;
- R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, alkoxycarbonyl, carboxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylmethyl, carboxymethyl, aminocarbonylmethyl, alkylaminocarbonylmethyl, dialkylaminocarbonylmethyl, hydroxy, alkoxy, di- or trifluoromethoxy, halogen, trifluoromethyl, cycloalkyl or alkyl;
- or two of the three substituents (R.sup.4, R.sup.5 and R.sup.6) may together be methylenedioxy or benzo such that they together with the benzene ring to which they are attached form naphthyl;
- R.sup.7, R.sup.8 and R.sup.9 are independently hydrogen, alkoxycarbonyl, carboxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylmethyl, carboxymethyl, aminocarbonylmethyl, alkylaminocarbonylmethyl, dialkylaminocarbonylmethyl, hydroxy, alkoxy, di- or trifluoromethoxy, halogen, trifluoromethyl, cycloalkyl or alkyl;
- or two of the three substituents (R.sup.7, R.sup.8 and R.sup.9) may together be methylenedioxy or benzo such that they together with the benzene ring to which they are attached form naphthyl;
- and
- m is the integer 0 or 1;
- provided that the heterocycle must be other than a 2-hydroxypyridine, 2-oxopyridine, 3,4-dihydro-2-hydroxypyridine, 3,4-dihydro-2-oxopyridine or 2,1,3-benzothiadiazole.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula ##STR45## or pharmaceutically acceptable salts thereof where R.sup.1 is hydrogen, hydroxy, alkoxy, nitro, amino, alkylsulfonylamino, acylamino, alkylsulfonyl, alkyl, cycloalkyl, phenyl, hydroxymethyl, cyano, aminocarbonyl, halogen or trifluoromethyl;
- R.sup.2 and R.sup.3 together with the carbon atoms to which they are attached, form a heterocycle;
- R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, alkoxycarbonyl, carboxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylmethyl, carboxymethyl, aminocarbonylmethyl, alkylaminocarbonylmethyl, dialkylaminocarbonylmethyl, hydroxy, alkoxy, di- or trifluoromethoxy, halogen, trifluoromethyl, cycloalkyl or alkyl;
- or two of the three substituents (R.sup.4, R.sup.5 and R.sup.6) may together be methylenedioxy or benzo such that they together with the benzene ring to which they are attached form naphthyl;
- R.sup.7, R.sup.8 and R.sup.9 are independently hydrogen, alkoxycarbonyl, carboxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylmethyl, carboxymethyl, aminocarbonylmethyl, alkylaminocarbonylmethyl, dialkylaminocarbonylmethyl, hydroxy, alkoxy, di- or trifluoromethoxy, halogen, trifluoromethyl, cycloalkyl or alkyl;
- or two of the three substituents (R.sup.7, R.sup.8 and R.sup.9) may together be methylenedioxy or benzo such that they together with the benzene ring to which they are attached form naphthyl;
- and
- m is the integer 0 or 1;
- provided that the heterocycle must be other than a 2-hydroxypyridine, 2-oxopyridine, 3,4-dihydro-2-hydroxypyridine, 3,4-dihydro-2-oxopyridine or 2,1,3-benzothiadiazole.
A pharmaceutical composition comprising a beta.sub.1 or beta.sub.2 adrenergic blocker or stimulant, a pharmaceutically acceptable carrier and a compound of formula ##STR46## or pharmaceutically acceptable salts thereof where R.sup.1 is hydrogen, hydroxy, alkoxy, nitro, amino, alkylsulfonylamino, acylamino, alkylsulfonyl, alkyl, cycloalkyl, phenyl, hydroxymethyl, cyano, aminocarbonyl, halogen or trifluoromethyl;
- R.sup.2 and R.sup.3 together with the carbon atoms to which they are attached, form a heterocycle;
- R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, alkoxycarbonyl, carboxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylmethyl, carboxymethyl, aminocarbonylmethyl, alkylaminocarbonylmethyl, dialkylaminocarbonylmethyl, hydroxy, alkoxy, di- or trifluoromethoxy, halogen, trifluoromethyl, cycloalkyl or alkyl;
- or two of the three substituents (R.sup.4, R.sup.5 and R.sup.6) may together be methylenedioxy or benzo such that they together with the benzene ring to which they are attached form naphthyl;
- R.sup.7, R.sup.8 and R.sup.9 are independently hydrogen, alkoxycarbonyl, carboxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylmethyl, carboxymethyl, aminocarbonylmethyl, alkylaminocarbonylmethyl, dialkylaminocarbonylmethyl, hydroxy, alkoxy, di- or trifluoromethoxy, halogen, trifluoromethyl, cycloalkyl or alkyl;
- or two of the three substituents (R.sup.7, R.sup.8 and R.sup.9) may together be methylenedioxy or benzo such that they together with the benzene ring to which they are attached form naphthyl;
- and
- m is the integer 0 or 1;
- provided that the heterocycle must be other than a 2-hydroxypyridine, 2-oxopyridine, 3,4-dihydro-2-hydroxypyridine, 3,4-dihydro-2-oxopyridine or 2,1,3-benzothiadiazole.
Dependencies are inferred from the claim text.