Substituted 1,3-diphenylprop-2-en-1-one derivatives and preparation and uses thereof

• US 7,943,661 B2
• Filed: 07/08/2003
• Issued: 05/17/2011
• Est. Priority Date: 07/08/2002
• Status: Active Grant

• Current Assignee: Genfit SA
• Original Assignee: Genfit SA
• Inventors: Najib, Jamila, Caumont-Bertrand, Karine
• Primary Examiner(s): Loewe; Sun Jae Y
• Application Number:
  US10/520,079
• Publication Number:
  US 20050176808A1
• Time in Patent Office: 2,870 Days
• Field of Search: None
• US Class Current: 514/432
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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: 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 67/30 by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
• CPC Class Codes: C07C 67/343 by increase in the number of carbon atoms
• 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 novel substituted 1,3-diphenylprop-2-en-1-one derivatives, pharmaceutical compositions comprising same, their therapeutic uses, in particular for treating cerebral ischemia. The invention also concerns a method for preparing said derivatives.

Claims

1. A compound of formula (I)

2. The compound of according to claim 1, wherein both G1 and G4 are sulfur.

3. The compound according to claim 1, wherein X₂ is hydrogen.

4. The compound according to claim 1, wherein X₁ is -G1-R1.

5. The compound according to claim 1, wherein X₁ is -G1-R1 and G1 is oxygen.

6. The compound according to claim 1, wherein X₁ is -G1-R1 and G1 is sulfur.

7. The compound according to claim 1, wherein X₄ is -G4-R4 group.

8. The compound according to claim 1, wherein X₄ is -G4-R4 and G4 is oxygen.

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

10. The compound according to claim 1 wherein X₁ is a halogen.

11. The compound according to claim 1, wherein X₄ is OC(CH₃)₂COOR₆.

12. The compound according to claim 1, wherein X₄ represents SC(CH₃)₂COOR₆.

15. A method for preparing a compound of claim 1, comprising contacting in basic or acidic medium at least one compound corresponding to formula (A) with at least one compound corresponding to formula (B):

16. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of claim 1.

17. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of claim 1, in a form for the treatment of a cerebral ischemia.

13. A compound selected in the group consisting of:

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

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

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

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

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

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

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

1-[4-heptylphenyl]-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.

14. A compound selected in the group consisting of:

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.