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US 5,629,319 AGranted
Hypoglycemic agent from cryptolepis
AssigneeShaman Pharmaceuticals, Inc.
InventorsJian Luo, Diana M. Fort, Donald E. Bierer, Reimar C. Bruening
Life of this patent
Estimating the term…
Abstract
The use of extracts from Cryptolepis sp. or quindoline alkaloids such quindoline and cryptolepine contained therein as hypoglycemic agents, as well as methods for obtaining the hypoglycemic agents are described. According to a preferred embodiment, the extracts are derived from Cryptolepis sanguinolenta. As hypoglycemic agents, the extracts or quindoline alkaloids such as quindoline or cryptolepine are useful for treating insulin-dependent (type I) and non-insulin-dependent (type II) diabetes.
Claims11
A method for reducing the blood glucose of a mammal, comprising administering to said mammal a hypoglycemically effective amount of a composition comprising a compound having the following structure or a pharmaceutically acceptable salt thereof ##STR7## said compound selected from group consisting of:
- (a) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.5 =CH.sub.3 ;
- (b) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.5 is selected from the group of ethyl, isopropyl, benzyl, 4-hydroxybenzyl, 4-dimethylaminobenzyl, 4-chlorobenzyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-dimethylaminophenyl, 4-chlorophenyl, 2-pyridino, 3-pyridino, 4-pyridino, 2-imidazol, 4-imidazol, 2-hydroxybenzyl, 3-hydroxybenzyl, 2-dimethylaminobenzyl, 3-dimethylaminobenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-imidazolylmethyl, 4-imidazolymethyl, 4-bromophenyl, 4-fluorophenyl, cyclopropyl, and isobutyl;
- (c) where R.sub.1, R.sub.4, R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.2 =R.sub.3 =--CH.sub.2 --O--CH.sub.2 --, and R.sub.5 is selected from the group consisting of ethyl, isopropyl, benzyl, 4-hydroxybenzyl, 4-dimethylaminobenzyl, 4-chlorobenzyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-dimethylaminophenyl, 4-chlorophenyl, 2-pyridino, 3-pyridino, 4-pyridino, 2-imidazol, 4-imidazol, 2-hydroxybenzyl, 3-hydroxybenzyl, 2-dimethylaminobenzyl, 3-dimethylaminobenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-imidazolylmethyl, 4-imidazolymethyl, 4-bromophenyl, 4-fluorophenyl, cyclopropyl, and isobutyl;
- (d) where R.sub.1 -R.sub.4, R.sub.6 -R.sub.7 and R.sub.11 =H, R.sub.8 =R.sub.9 =--CH.sub.2 --O--CH.sub.2 --, and R.sub.5 is selected from the group consisting of ethyl, isopropyl, benzyl, 4-hydroxybenzyl, 4-dimethylaminobenzyl, 4-chlorobenzyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-dimethylaminophenyl, 4-chlorophenyl, 2-pyridino, 3-pyridino, 4-pyridino, 2-imidazol, 4-imidazol, 2-hydroxybenzyl, 3-hydroxybenzyl, 2-dimethylaminobenzyl, 3-dimethylaminobenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-imidazolylmethyl, 4-imidazolymethyl, 4-bromophenyl, 4-fluorophenyl, cyclopropyl, and isobutyl;
- (e) where R.sub.1 -R.sub.3, R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.4 -R.sub.5 =--CH.sub.2 CH.sub.2 --;
- (f) where R.sub.1 -R.sub.3, R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.4 -R.sub.5 =--CH.sub.2 CH.sub.2 CH.sub.2 --;
- (g) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.5 =CH.sub.3, and 10a, 11=dihydro;
- (h) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.5 =CH.sub.3, and 5a, 5b=dihydro;
- (i) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.5 =CH.sub.3, and 5a, 5b, 10a, 11=tetrahydro;
- (j) where R.sub.1 -R.sub.9 and R.sub.11 =H, and 9a,10=dihydro;
- and
- (k) where R.sub.1 -R.sub.9 and R.sub.11 =H, and 10-methyl.
9 more elements
A method for treatment of diabetes mellitus, comprising administering, to a mammal suffering from diabetes mellitus, a therapeutically effective amount of a composition comprising a compound having the following structure or a pharmaceutically acceptable salt thereof ##STR8## (a) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.5 =CH.sub.3 ;
- (b) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.5 is selected from the group of ethyl, isopropyl, benzyl, 4-hydroxybenzyl, 4-dimethylaminobenzyl, 4-chlorobenzyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-dimethylaminophenyl, 4-chlorophenyl, 2-pyridino, 3-pyridino, 4-pyridino, 2-imidazol, 4-imidazol, 2-hydroxybenzyl, 3-hydroxybenzyl, 2-dimethylaminobenzyl, 3-dimethylaminobenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl-2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-imidazolylmethyl, 4-imidazolymethyl, 4-bromophenyl, 4-fluorophenyl, cyclopropyl, and isobutyl;
- (c) where R.sub.1, R.sub.4, R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.2 =R.sub.3 =--CH.sub.2 -O-CH.sub.2 --, and R.sub.5 is selected from the group consisting of ethyl, isopropyl, benzyl, 4-hydroxybenzyl, 4-dimethylaminobenzyl, 4-chlorobenzyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-dimethylaminophenyl, 4-chlorophenyl-2-pyridino, 3-pyridino, 4-pyridino, 2-imidazol, 4-imidazol, 2-hydroxybenzyl, 3-hydroxybenzyl, 2-dimethylaminobenzyl, 3-dimethylaminobenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-imidazolylmethyl, 4-imidazolymethyl, 4-bromophenyl, 4-fluorophenyl, cyclopropyl, and isobutyl;
- (d) where R.sub.1 -R.sub.4, R.sub.6 -R.sub.7 and R.sub.11 =H, R.sub.8 =R.sub.9 =--CH.sub.2 --O--CH.sub.2 --, and R.sub.5 is selected from the group consisting of ethyl, isopropyl, benzyl, 4-hydroxybenzyl, 4-dimethylaminobenzyl, 4-chlorobenzyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-hydroxyphenyl, 4-dimethylaminophenyl, 4-chlorophenyl, 2-pyridino, 3-pyridino, 4-pyridino, 2-imidazol, 4-imidazol, 2-hydroxybenzyl, xybenzyl, 3-hydroxybenzyl, 2-dimethylaminobenzyl, 3-dimethylaminobenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-imidazolylmethyl, 4-imidazolymethyl, 4-bromophenyl, 4-fluorophenyl, cyclopropyl, and isobutyl;
- (e) where R.sub.1 -R.sub.3, R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.4 -R.sub.5 =--CH.sub.2 CH.sub.2 --;
- (f) where R.sub.1 -R.sub.3, R.sub.6 -R.sub.9 and R.sub.11 =H, and R.sub.4 -R.sub.5 =--CH.sub.2 CH.sub.2 CH.sub.2 --;
- (g) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.5 =CH.sub.3, and 10a, 11=dihydro;
- (h) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.5 =CH.sub.3, and 5a, 5b=dihydro;
- (i) where R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 and R.sub.11 =H, R.sub.5 =CH.sub.3, and 5a, 5b, 10a, 11=tetrahydro;
- (j) where R.sub.1 -R.sub.9 and R.sub.11 =H, and 9a,10=dihydro;
- and
- (k) where R.sub.1 -R.sub.9 and R.sub.11 =H, and 10-methyl.
8 more elements
A method for reducing the blood glucose of a mammal, comprising administering to said mammal a hypoglycemically effective amount of a composition comprising a compound having the following structure or a pharmaceutically acceptable salt thereof ##STR9## where R=CH.sub.3.
A method for treatment of diabetes mellitus, comprising administering, to a mammal suffering from diabetes mellitus, a therapeutically effective amount of a composition comprising a compound having the following structure or a pharmaceutically acceptable salt thereof ##STR10## where R=CH.sub.3.
Dependencies are inferred from the claim text.