Composition based on substituted 1,3-diphenylprop-2-en-1-one derivatives, preparation and uses thereof

• US 7,632,870 B2
• Filed: 07/08/2003
• Issued: 12/15/2009
• Est. Priority Date: 07/08/2002
• Status: Active Grant

• Current Assignee: Genfit SA
• Original Assignee: Genfit SA
• Inventors: Caumont-Bertrand, Karine, Najib, Jamila
• Primary Examiner(s): Hui; San-ming
• Assistant Examiner(s): ZAREK, PAUL E
• Application Number:
  US10/520,078
• Publication Number:
  US 20050171149A1
• Time in Patent Office: 2,352 Days
• Field of Search: None
• US Class Current: 514/685
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/055 the aromatic ring being substituted by halogen
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07C 323/22 : containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• CPC Class Codes: C07C 323/52 : the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 59/90 : containing singly bound oxygen-containing groups
• CPC Class Codes: C07C 69/712 : the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/738 : Esters of keto-carboxylic acids or aldehydo-carboxylic acids

Abstract

The invention concerns compositions comprising substituted 1,3-diphenylprop-2-en-1-one derivatives designed for therapeutic use. The inventive compositions are useful in particular for preventing or treating cardiovascular diseases, syndrome X, Ia restenosis, diabetes, obesity, hypertension, inflammatory diseases, cancers or neoplasms (benign or malignant tumors), neurodegenerative, dermatological diseases and disorders related to oxidative stress, for preventing or treating the effects of ageing in general and for example skin ageing, in particular in the field of cosmetics (occurrence of wrinkles and the like).

Claims

1. A pharmaceutical composition, comprising one or more pharmaceutically acceptable excipients or vehicles and at least one substituted 1,3-diphenylprop-2-en-1-one derivative represented by formula (I) below:

2. The composition according to claim 1, wherein both G1 and G4 represent an oxygen atom.

3. The composition according to claim 1, wherein X1 is a -G1-R1 group in which G1 is an oxygen atom and R1 is an unsubstituted alkyl group containing from two to seven carbon atoms.

4. The composition according to claim 1, wherein X1 represents a group corresponding to the formula -G1-R1, where G1 represents a sulphur atom and R1 is an unsubstituted alkyl group containing one or two carbon atoms.

5. The composition according to claim 1, wherein G4 is an oxygen atom, and X3 and X5 respectively represent R3 and R5, with R3 and R5 being alkyl groups having one or two carbon atoms.

6. The composition according to claim 1, wherein X1 represents a halogen.

7. The composition according to claim 1, wherein X4 represents —

OC(CH₃)₂COOR₆.

8. The composition according to claim 1, wherein X4 represents —

OC(CH₃)₂COOH.

9. The composition according to claim 1, wherein the derivative is selected in the group consisting of:

1-[4-chlorophenyl]-3-[3,5-dimethyl-4-tertbutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-chlorophenyl]-3-[3,5-dimethyl-4-isopropyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-chlorophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3,5-dimethyl-4-tertbutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1 -one,

1-[4-methylthiophenyl]-3-[3,5-dimethyl-4-isopropyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-hexyloxyphenyl]-3-[3,5-dimethyl-4-tertbutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-hexyloxyphenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3,5-dimethyl-4-tertbutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one, and

1-[4-bromophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one.

10. The composition according to claim 1, wherein the derivative is selected in the group consisting of:

1-[4-chlorophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-hexyloxyphenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one, and

1-[4-bromophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one.

11. A method for the treatment of diabetes, atherosclerosis or obesity comprising administering to a subject in need thereof, an effective amount of a composition according to claim 1.