Oxy substituted chalcones as antihyperglycemic and antidyslipidemic agents
OwnerRam Pratap, Mavurapu Satyanarayana +7inventors
InventorsRam Pratap, Mavurapu Satyanarayana, Chandeshwar Nath, Ram Raghubir, Anju Puri, Ramesh Chander, Priti Tiwari, Brajendra Tripathi, Arvind Srivastava
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Abstract
The present invention provides novel substituted chalcone derivatives which exhibit anti-hyperglycemic and anti-dyslipedemic activity. The invention also provides a method for treating type II diabetes and associated hyperlipidemic conditions in a mammal by administering the compounds of the present invention and compositions containing these derivatives.
Claims25
A compound having formula (I) or a pharmaceutically acceptable salt thereof:
- wherein
- R1, R2 and R3 are selected from H, OH, O-alkyl, O-phenyl, O-substituted phenyl or a combination thereof;
- where Z is an alkane having up to 5 carbon atoms;
- R is propanolamine wherein amino groups are selected from t-butyl amine, n-butyl amine, i-butyl amine, i-propyl amine, 4-phenyl piperazine-1-yl amine, 4-(2-methoxyphenyl)-piperazin-1yl amine, and 3,4-dimethoxy phenethyl amine and Ar is thiazolidinedione methylene phenoxy.
A composition comprising a compound of formula I along with a lipid lowering agent and/or a sugar lowering agent.
A process for preparing a compound of formula I, comprising the steps of:
- (i) reacting hydroxy acetophenone and substituted benzaldehyde using aqueous sodium hydroxide in methanol at room temperature to obtain chalcones;
- (ii) reacting chalcones obtained in step (i) with epichlorohydrin using sodium hydride as base in dry dimethyl formamide to obtain epoxide;
- and
- (iii) heating epoxide obtained in step (ii) under reflux at room temperature with suitable amines in methanol to yield corresponding propanolamines.
A process for preparing a compound of formula I comprising the steps of:
- (i) reacting chalcone with dibromo alkane in presence of K2CO3 and acetone at room temperature to get bromo alkoxy chalcone;
- and
- (ii) reacting bromo alkoxy chalcone obtained in step (i) with 4-(Thiazolidin-2,4-dione-5-ylidinemethyl)-phenol, in presence of K2CO3 and dimethyl formamide at room temperature to obtain corresponding chalcone derived thiazolidinediones.
A method of treating type II diabetes in mammals, said method comprising the step of administering a pharmaceutically effective amount of a compound of formula I, or pharmaceutical salts thereof, optionally with other diabetic and lipid lowering agents
- wherein
- R1, R2 and R3 are selected from H, OH, O-alkyl, O-phenyl, O-substituted phenyl or a combination thereof;
- where Z is an alkane having up to 5 carbon atoms;
- R is propanolamine wherein amino groups are selected from t-butyl amine, n-butyl amine, i-butyl amine, i-propyl amine, 4-phenyl piperazine-1-yl amine, 4-(2-methoxyphenyl)-piperazin-1yl amine, and 3,4-dimethoxy phenethyl amine and Ar is thiazolidinedione methylene phenoxy.
A method of treating hyperlipidemic conditions in mammals, said method comprising the step of administering a pharmaceutically effective amount of a compound of formula I, or pharmaceutical salts thereof, optionally with other diabetic and lipid lowering agents
- wherein
- R1, R2 and R3 are selected from H, OH, O-alkyl, O-phenyl, O-substituted phenyl or a combination thereof;
- where Z is an alkane having up to 5 carbon atoms;
- R is propanolamine wherein amino groups are selected from t-butyl amine, n-butyl amine, i-butyl amine, i-propyl amine, 4-phenyl piperazine-1-yl amine, 4-(2-methoxyphenyl)-piperazin-1yl amine, and 3,4-dimethoxy phenethyl amine and Ar is thiazolidinedione methylene phenoxy.
A method of treating macrovascular conditions such as retinopathy and nephropathy in mammals, said method comprising the step of administering a pharmaceutically effective amount of a compound of formula I, or pharmaceutical salts thereof, optionally with other diabetic and lipid lowering agents
- wherein
- R1, R2 and R3 are selected from H, OH, O-alkyl, O-phenyl, O-substituted phenyl or a combination thereof;
- where Z is an alkane having up to 5 carbon atoms;
- R is propanolamine wherein amino groups are selected from t-butyl amine, n-butyl amine, i-butyl amine, i-propyl amine, 4-phenyl piperazine-1-yl amine, 4-(2-methoxyphenyl)-piperazin-1yl amine, and 3,4-dimethoxy phenethyl amine and Ar is thiazolidinedione methylene phenoxy.
Dependencies are inferred from the claim text.