Antidiabetic 3,4,5-trihydroxypiperidines
AssigneeBayer Aktiengesellschaft
InventorsBodo Junge, Hans P. Krause, Lutz Muller, Walter Puls
Life of this patent
Estimating the term…
Abstract
The invention includes certain 3,4,5-trihydroxypiperidine compounds, methods for their preparation, compositions containing said 3,4,5-trihydroxypiperidine compounds and methods for the use of said compounds and compositions. The subject matter of the invention is useful against diabetes, hyperlipaemia and adiposity as well as in animal nutrition.
Claims32
A compound of the formula ##STR264## in which R.sub.1 is C.sub.5 -C.sub.30 alkyl, C.sub.2 -C.sub.18 alkenyl, C.sub.2 -C.sub.18 alkinyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, C.sub.3 -C.sub.8 -cycloalkinyl, phenyl (a), C.sub.1 -C.sub.2 and C.sub.7 -C.sub.30 alkyl substituted by phenyl (b) or substituted C.sub.1 -C.sub.4 -alkyl said C.sub.5 -C.sub.30 alkyl, cycloalkyl, cycloalkenyl and cycloalkinyl being unsubstituted or substituted by hydroxy, C.sub.1 -C.sub.4 -alkoxy, acyloxy, amino, mono- C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, acylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, halogen, C.sub.1 -C.sub.4 alkylcarbonyl, carboxyl nitro, cyano, formyl, sulfo, a heterocyclic radical derived from a hexose or pentose, attached to the alkyl moiety directly via a ring atom or via an --O--, --S-- or --NH-bridge or naphthyl said phenyl (a) being unsubstituted or substituted by C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 chloroalkyl, C.sub.1 to C.sub.10 nitroalkyl, C.sub.1 to C.sub.10 cyanoalkyl, C.sub.1 to C.sub.10 alkenyl, hydroxyl, C.sub.1 to C.sub.4 alkoxy, amino, mono-C.sub.1 to C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, carboxyl, C.sub.1 -C.sub.4 carbalkoxy, sulfo, C.sub.1 -C.sub.4 alkylsulfonyl, phenylsulfonyl, aminosulfonyl, C.sub.1 -C.sub.4 alkylaminosulfonyl, di-C.sub.1 -C.sub.4 alkylaminosulfonyl, nitro, cyano, formyl, C.sub.1 -C.sub.4 alkylcarbonylamino, C.sub.1 -C.sub.4 alkylcarbonyl, benzoyl, benzylcarbonyl or phenylethylcarbonyl;
- said substituted C.sub.1 -C.sub.4 alkyl being substituted by hydroxy, C.sub.1 -C.sub.4 -alkoxy, acyloxy, amino, mono- C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, acylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, halogen, C.sub.1 - C.sub.4 alkylcarbonyl, carboxyl nitro, cyano, formyl, sulfo, a heterocyclic radical derived from a hexose or pentose, attached to the alkyl moiety directly via a ring atom or via an --O--, --S-- or --NH--bridge or naphthyl, said acyl being derived from an aliphatic carboxylic acid having from 1 to 7 C-atoms, a phenyl carboxylic acid, unsubstituted or substituted by carboxy, hydroxy, halogen, C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, nitro or amino, or a 5- or 6-membered aromatic heterocyclic carboxylic acid containing from 1 to 3 hetero-atoms each of which is N, O or S, unsubstituted or substituted by C.sub.1 to C.sub.4 alkyl, chlorine, bromine or amino;
- said naphthyl and phenyl (b) being unsubstituted or substituted by hydroxyl, amino, C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, carboxy, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.4 alkylthio, mercapto, C.sub.1 -C.sub.4 alkylsulfonyl, sulfo, aminosulfonyl or C.sub.1 -C.sub.4 alkylaminosulfonyl R.sub.2 is ##STR265## wherein phenyl is unsubstituted or substituted by methyl, ethyl, methoxy, chlorine, bromine or nitro, R.sub.3 is --H, --CH.sub.3, --CH.sub.2 OH, --CH.sub.2 --NH.sub.2, NHR'--CH.sub.2 --, NR'R"--CH.sub.2 --, R'CONH--CH.sub.2, R'CO--NR"CH.sub.2 --, R'O--CH.sub.2, R'COOCH.sub.2 --, R'SO.sub.2 NHCH.sub.2 --, R'SO.sub.2 --NR"CH.sub.2 --, R'NH--CO--NH--CH.sub.2 --, R'NHCS--NH--CH.sub.2, R'O--CO--NH--CH.sub.2 --, wherein R' and R" are the same or different and each has the meaning hydrogen or C.sub.1 -C.sub.30 alkyl, C.sub.2 -C.sub.18 alkenyl, C.sub.2 -C.sub.18 alkinyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, C.sub.3 -C.sub.8 -cycloalkinyl or phenyl (a), said alkyl, cycloalkyl, cycloalkenyl and cycloalkinyl being unsubstituted or substituted by hydroxy, C.sub.1 -C.sub.4 -alkoxy, acyloxy, amino, mono- C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, acylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, halogen, C.sub.1 -C.sub.4 alkylcarbonyl, carboxyl, nitro, cyano, formyl, sulfo, a heterocyclic radical derived from a hexose or pentose, attached to the alkyl moiety directly via a ring atom or via an --O--, --S-- or --NH--bridge, naphthyl or phenyl (b) said acyl being derived from an aliphatic carboxylic acid having from 1 to 7 C-atoms, a phenyl carboxylic acid, unsubstituted or substituted by carboxy, hydroxy, halogen, C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, nitro or amino, or a 5- or 6-membered aromatic heterocyclic carboxylic acid containing from 1 to 3 hetero-atoms each of which is N, O or S, unsubstituted or substituted by C.sub.1 to C.sub.4 alkyl, chlorine, bromine or amino;
- said phenyl (a) being unsubstituted or substituted by C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 chloroalkyl, C.sub.1 to C.sub.10 nitroalkyl, C.sub.1 to C.sub.10 cyanoalkyl, C.sub.1 to C.sub.10 alkenyl, hydroxyl, C.sub.1 to C.sub.4 alkoxy, amino, mono-C.sub.1 to C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, carboxyl, C.sub.1 -C.sub.4 -carbaloxy, sulfo, C.sub.1 -C.sub.4 alkylsulfonyl, phenylsulfonyl, aminosulfonyl, C.sub.1 -C.sub.4 alkylaminosulfonyl, di-C.sub.1 -C.sub.4 alkylaminosulfonyl, nitro, cyano, formyl, C.sub.1 -C.sub.4 alkylcarbonylamino, C.sub.1 -C.sub. 4 alkylcarbonyl, benzoyl, benzylcarbonyl or phenylethylcarbonyl;
- said napthyl and phenyl (b) being unsubstituted or substituted by hydroxyl, amino, C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, carboxy, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.4 alkylthio, mercapto, C.sub.1 -C.sub.4 alkylsulfonyl, sulfo, aminosulfonyl or C.sub.1 -C.sub.4 alkylaminosulfonyl.
A compound of the formula ##STR266## wherein R.sub.2 is ##STR267## wherein phenyl is unsubstituted or substituted by methyl, ethyl, methoxy, chlorine, bromine, or nitro.
A compound of the formula ##STR268## wherein R.sub.2 is ##STR269## wherein phenyl is unsubstituted or substituted by methyl, ethyl, methoxy, chlorine, bromine or nitro and R.sub.3 is CH.sub.2 --NH.sub.2, --CH.sub.2 --NHR', --CH.sub.2 --NR'R"--, --CH.sub.2 --NHCOR', --CH.sub.2 --NR"--COR', --CH.sub.2 OR', --CH.sub.2 --OCOR', --CH.sub.2 --NHSO.sub.2 R', --CH.sub.2 --NR"--SO.sub.2 R', --CH.sub.2 --NHCONH.sub.2, --CH.sub.2 --NHCONHR', --CH.sub.2 --NHCSNH.sub.2, --CH.sub.2 --NHCSNHR', --CH.sub.2 --NH--COOR' wherein R' and R" are the same or different and each is C.sub.1 -C.sub.30 alkyl, C.sub.2 -C.sub.18 alkenyl, C.sub.2 -C.sub.18 alkinyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, C.sub.3 -C.sub.8 -cycloalkinyl or phenyl (a), said alkyl, cycloalkyl, cycloalkenyl and cycloalkinyl being unsubstituted or substituted by hydroxy, C.sub.1 -C.sub.4 -alkoxy, acyloxy, amino, mono-C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, acylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, halogen, C.sub.1 -C.sub.4 alkylcarbonyl, carboxyl, nitro, cyano, formyl, sulfo, a heterocyclic radical derived from a hexose or pentose, attached to the alkyl moiety directly via a ring atom or via an --O--, --S-- or --NH-bridge, naphthyl or phenyl (b) said acyl being derived from an aliphatic carboxylic acid having from 1 to 7 C-atoms, a phenyl carboxylic acid, unsubstituted or substituted by carboxy, hydroxy, halogen, C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.4 alkoxy, nitro or amino, or a 5- or 6-membered aromatic heterocyclic carboxylic acid containing from 1 to 3 hetero-atoms each of which is N, O or S, unsubstituted or substituted by C.sub.1 to C.sub.4 alkyl, chlorine, bromine or amino;
- said phenyl (a) being unsubstituted or substituted by C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 chloroalkyl, C.sub.1 to C.sub.10 nitroalkyl, C.sub.1 to C.sub.10 cyanoalkyl, C.sub.1 to C.sub.10 alkenyl, hydroxyl, C.sub.1 to C.sub.4 alkoxy, amino, mono-C.sub.1 to C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, mercapto, C.sub.1 -C.sub.4 alkylthio, carboxyl, C.sub.1 -C.sub.4 -carbalkoxy, sulfo, C.sub.1 -C.sub.4 alkylsulfonyl, phenylsulfonyl, aminosulfonyl, C.sub.1 -C.sub.4 alkylaminosulfonyl, di-C.sub.1 -C.sub.4 alkylaminosulfonyl, nitro, cyano, formyl, C.sub.1 -C.sub.4 alkylcarbonylamino, C.sub.1 -C.sub.4 alkylcarbonyl, benzoyl, benzylcarbonyl or phenylethylcarbonyl;
- said naphthyl and phenyl (b) being unsubstituted or substituted by hydroxyl, amino, C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 alkoxy, nitro, cyano, carboxy, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.4 alkylthio, mercapto, C.sub.1 -C.sub.4 alkylsulfonyl, sulfo, aminosulfonyl or C.sub.1 -C.sub.4 alkylaminosulfonyl.
A compound of the formula ##STR270## wherein R.sub.1 is C.sub.1 -C.sub.2 and C.sub.7 -C.sub.30 alkyl substituted by phenyl, said phenyl being unsubstituted or substituted by hydroxyl, amino, C.sub.1 -C.sub.4 alkylamino, di-C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 alkoxy, cyano, carboxy, C.sub.1 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.6 alkyl or halogen.
A compound of the formula:
- ##STR272## wherein R.sub.1 is C.sub.2 -C.sub.18 alkenyl.
Dependencies are inferred from the claim text.