Aminosteroids for the Treatment of a PTP1B Associated Disease
This application is directed to the use of aminosteroid compounds for the selective inhibition of the enzyme PTP1B in a mammal for the treatment of diabetes.
1 .- 9 . (canceled)
10 . A compound or pharmaceutically acceptable salt thereof selected from the group consisting of:
11 . A pharmaceutical composition comprising the compound of claim 10 and a pharmaceutically acceptable diluent or carrier.
12 . A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 10 or a pharmaceutically acceptable salt thereof.
13 . The method of claim 12 , wherein the disorder is selected from the group consisting of diabetes, obesity, high serum cholesterol, sleep apnea and nonalcoholic steatohepatitis.
14 . A compound of formula
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 =—NH(CH 2 ) 1-4 —NH—R 6 , H,
R 6 =—(CH 2 ) 1-4 —NH—R 7 or —(CH 2 ) 0-3 —C 1 -C 5 alkyl or —(CH 2 ) 0-3 —C 3 -C 7 cycloalkyl or —(CH 2 ) 0-3 —C 3 -C 6 heterocycloalkyl or —(CH 2 ) 0-3 -aromatic or —(CH 2 ) 0-3 -heteroaromatic or H;
R 7 =—(CH 2 ) 1-4 —NH 2 or —(CH 2 ) 1-4 —NH—(C 1 -C 5 alkyl) or —(CH 2 ) 1-4 —NH—(C 3 -C 6 heterocycloalkyl) or —(CH 2 ) 1-4 —NH-aromatic or —(CH 2 ) 1-4 —NH-heteroaromatic or H;
R 2 =—OH or H;
R 3 =—OH or NH—R 8 or methylsulfone or methyl sulfide or H;
R 8 =acetyl, —SO 2 —CH 3 or —C(O)OCH 3 ;
R 4 =—OH or H; and
15 . A compound of formula
or a pharmaceutically acceptable salt thereof,
wherein:
X 2 =—OH or H;
X 3 =H, —OH, —S(O) 2 —CH 3 , —NHC(O)—CH 3 , —NHC(O)—OCH 3 , —NHC(O)—SCH 3 , —NH—SO 2 CH 3 or —SCH 3 ;
X 4 =—OH or H; and
X 5 =H or —CH 3 .
16 . A compound of formula
or a pharmaceutically acceptable salt thereof,
wherein:
X 2 =—OH or H;
X 7 =—OH or H;
X 4 =—OH or H; and
X 8 =—OH or H.
17 . A pharmaceutical composition comprising the compound of claim 14 and a pharmaceutically acceptable diluent or carrier.
18 . A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 14 , or a pharmaceutically acceptable salt thereof.
19 . The method of claim 18 , wherein the disorder is selected from the group consisting of diabetes, obesity, high serum cholesterol, sleep apnea and nonalcoholic steatohepatitis.
20 . A pharmaceutical composition comprising the compound of claim 15 and a pharmaceutically acceptable diluent or carrier.
21 . A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 15 or a pharmaceutically acceptable salt thereof.
22 . The method of claim 21 , wherein the disorder is selected from the group consisting of diabetes, obesity, high serum cholesterol, sleep apnea and nonalcoholic steatohepatitis.
23 . A pharmaceutical composition comprising a compound of claim 16 and a pharmaceutically acceptable diluent or carrier.
24 . A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 16 , or a pharmaceutically acceptable salt thereof.
25 . The method of claim 24 , wherein the disorder is selected from the group consisting of diabetes, obesity, high serum cholesterol, sleep apnea and nonalcoholic steatohepatitis.