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

• US 8,058,308 B2
• Filed: 04/11/2011
• Issued: 11/15/2011
• Est. Priority Date: 07/08/2002
• Status: Expired due to Term

• Current Assignee: Genfit SA
• Original Assignee: Genfit SA
• Inventors: Najib, Jamila, Caumont-Bertrand, Karine
• Primary Examiner(s): Saeed, Kamal
• Assistant Examiner(s): Bianchi, Kristin
• Application Number:
  US13/083,659
• Publication Number:
  US 20110190515A1
• Time in Patent Office: 218 Days
• Field of Search: 514/456, 514/543, 514/571, 549/403, 560/53, 562/463, 562/431
• US Class Current: 514/456
• 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 selected in the group consisting of:

1-[2-hydroxy-4-ethoxycarbonyldimethylmethyloxyphenyl]-3-[3,5-ditertiobutyl-4-hydroxyphenyl]prop-2-en-1-one;

1-[2-hydroxy-4-carboxydimethylmethyloxyphenyl]-3-[3,5-ditertiobutyl-4-hydroxyphenyl]prop-2-en-1-one;

1-[2-hydroxy-4-chlorophenyl]-3-[4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[2-hydroxyphenyl]-3-[4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[2-hydroxyphenyl]-3-[3,5-dimethoxy-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[2-hydroxy-4-carboxydimethylmethyloxyphenyl]-3-[3,5-dibromo-4-hydroxyphenyl]prop-2-en-1-one;

1-[2-hydroxyphenyl]-3-[3-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[2-hydroxy-4-carboxydimethylmethyloxyphenyl]-3-[3-hydroxyphenyl]prop-2-en-1-one;

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

1-[2-hydroxy-4-carboxydimethylmethyloxyphenyl]-3-[4-methylthiophenyl]prop-2-en-1-one;

1-[2,4-dihydroxyphenyl]-3-[4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[2-hydroxyphenyl]-3-[4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[2-hydroxy-4-carboxydimethylmethyloxyphenyl]-3-[4-chlorophenyl]prop-2-en-1-one;

1-[2-hydroxyphenyl]-3-[4-carboxydimethylmethylthiophenyl]prop-2-en-1-one;

1-[4-chloro-2-hydroxyphenyl]-3-[4-carboxydimethylmethylthiophenyl]prop-2-en-1-one;

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

1-[4-methylthiophenyl]-3-[4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one;

1-[4-carboxydimethylmethyloxyphenyl]-3-[4-chlorophenyl]prop-2-en-1-one;

1-[4-carboxydimethylmethylthiophenyl]-3-[4-methylthiophenyl]prop-2-en-1-one;

1-[4-carboxydimethylmethyloxyphenyl]-3-[4-methylthiophenyl]prop-2-en-1-one;

1-[2-methoxyphenyl]-3-[3,5-dimethyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one;

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

2-(3,5-dimethyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl)-7-chloro-4H-1-benzopyran-4-one;

2-(3,5-dimethyl-4-carboxydimethylmethyloxyphenyl)-7-chloro-4H-1-benzopyran-4-one; and

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

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

4. 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.

5. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of claim 1, in a form for the treatment of a hemorrhagic stroke.

6. A method of treatment of a cerebral ischemia comprising administering, to a subject in need of such treatment, at least one compound of claim 1.

7. A method of treatment of a hemorrhagic stroke comprising administering, to a subject in need of such treatment, at least one compound of claim 1.

8. A method for neuroprotection in cerebral ischemia comprising administering, to a subject in need of such neuroprotection, at least one compound of claim 1.

2. A compound selected in the group consisting of:

1-[2-methoxyphenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one, 1-[2-methoxyphenyl]-3-[3,5-dimethyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one, and 1-[2-hydroxyphenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one.

9. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of claim 2.

10. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of claim 2, in a form for the treatment of a cerebral ischemia.

11. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound of claim 2, in a form for the treatment of a hemorrhagic stroke.

12. A method of treatment of a cerebral ischemia comprising administering, to a subject in need of such treatment, at least one compound of claim 2.

13. A method of treatment of a hemorrhagic stroke comprising administering, to a subject in need of such treatment, at least one compound of claim 2.

14. A method for neuroprotection in cerebral ischemia comprising administering, to a subject in need of such neuroprotection, at least one compound of claim 2.