Combinations of substituted 1,3-diphenylprop-2-en-1-one derivatives with other therapeutically active ingredients

• US 7,566,737 B2
• Filed: 07/26/2006
• Issued: 07/28/2009
• Est. Priority Date: 07/08/2002
• Status: Expired due to Term

• Current Assignee: Genfit SA
• Original Assignee: Genfit SA
• Inventors: Delhomel, Jean-François, Caumont-Bertrand, Karine
• Primary Examiner(s): Saeed; Kamal A
• Application Number:
  US11/493,040
• Publication Number:
  US 20070032543A1
• Time in Patent Office: 1,098 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 and combinations of said derivatives with other therapeutically active ingredients. The invention also concerns compositions comprising said derivatives or said combinations and uses thereof, for the treatment of cerebrovascular diseases, pathology related to inflammation, neurodegeneration, deregulations of lipid and/or glucose metabolism, cell proliferation and/or differentiation and/or skin or central nervous system ageing.

Claims

1. A pharmaceutical composition comprising, in a pharmaceutically acceptable support, at least one compound represented by formula (I) in association with another therapeutically active ingredient, wherein said compound is a substituted 1,3-diphenylprop-2-en-1-one derivative represented by formula (I) below:

2. The composition according to claim 1, wherein compounds are of formula (I) with the exception of compounds represented by formula (I) in which:

X1, X2, X3 and X5 each represent a hydrogen atom, X6 represents an oxygen atom and X4 represents a group corresponding to the formula —

O—

CR₈R₉—

COOR₁₀, where R₈ and R9, which are the same or different, represent a C1 to C2 alkyl group, and R₁₀ represents a hydrogen atom or a C1 to C7 alkyl group, and

X2, X3 and X5 each represent a hydrogen atom, X1 represents a halogen atom or a —

R1 or -G1-R1 group, where R1 represents an unsubstituted C1-C2 alkyl group and G1 represents an oxygen atom, X6 represents an oxygen atom and X4 represents a group corresponding to the formula —

O—

CR₁₁R₁₂—

COOR₁₀, where R₁₁ and R₁₂, which are the same or different, represent a hydrogen atom or a C1 to C2 alkyl group, and R₁₀ represents a hydrogen atom or a C1 to C7 alkyl group, and

X2 represents a hydrogen atom and X1 represents -G1-R1 where G1 represents an oxygen atom and R1 represents —

CH₂COOH.

3. The pharmaceutical composition according to claim 1, wherein the other therapeutically active ingredient is selected in the group consisting of antidiabetics, insulin, lipid-lowering and/or cholesterol-lowering molecules, anti-hypertension agents and hypotension agents, anti-platelet agents, anti-obesity agents, anti-inflammatories, anti-oxidant agents, agents used in the treatment of cardiac insufficiency, agents used for the treatment of coronary insufficiency, anti-neoplastic agents, anti-asthmatics, corticoids, vasodilatators and/or anti-ischemic agents.

4. The pharmaceutical composition according to claim 3, wherein the other therapeutically active ingredient is selected in the group consisting of:

The PPARγ

agonist rosiglitazone

The angiotensin II receptor antagonist irbesartan

The cholesterol absorption inhibitor ezetimibe

The HmGCoA inhibitor “

simvastatin”

Fenofibrate.

5. The composition according to claim 1 wherein compound of formula (I) is selected in the group consisting of:

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

1-[2-hydroxy-4-chlorophenyl]-3-[4-isopropyloxycarbonyl dimethylmethyloxyphenyl]prop-2-en-1-one,

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

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

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

1-[2-methylcarbonyloxyphenyl]-3-[4-isopropyloxycarbonyldimethyl methyloxyphenyl]prop-2-en-1-one,

1-[2-hydroxyphenyl]-3-[4-carboxydimethylmethyloxyphenyl]-1-hydroxyiminoprop-2-ene,

1-[2-hydroxyphenyl]-3-[4-isopropyloxycarbonyldimethylmethyloxyphenyl]-1-hydroxyiminoprop-2-ene,

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

1-[2-hydroxy-4-isopropyloxycarbonyldimethylmethyloxyphenyl]-3-[3,5-ditertbutyl-4-hydroxyphenyl]prop-2-en-1-one,

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

1-[2-hydroxyphenyl]-3-[3-carboxydimethylmethyloxy-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxyphenyl]-3-[3-isopropyloxycarbonyldimethylmethyloxy-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxy-4-chlorophenyl]-3-[3-carboxydimethylmethyloxy-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxy-4-chlorophenyl]-3-[3-isopropyloxycarbonyldimethylmethyloxy-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxyphenyl]-3-[3-carboxydimethylmethyl-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxyphenyl]-3-[3-isopropyloxycarbonyldimethylmethyl-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxy-4-chlorophenyl]-3-[3-carboxydimethylmethyl-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

1-[2-hydroxy-4-chlorophenyl]-3-[3-isopropyloxycarbonyldimethylmethyl-4-hydroxy-5-tertbutylphenyl]prop-2-en-1-one,

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

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

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

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

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

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

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

1-[2-hydroxy-4-chlorophenyl]-3-[3,4-dihydroxy-5-isopropyloxycarbonyldimethylmethyloxyphenyl]-2-propen-1-one,

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

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

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

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

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

1-[2-hydroxyphenyl]-3-[3,5-dimethyl-4-isopropyloxycarbonyl dimethylmethyloxyphenyl]prop-2-en-1-one,

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

1-[2-hydroxyphenyl]-3-[3-isopropyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

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

1-[2-hydroxyphenyl]-3-[4-isopropyloxycarbonyldimethylmethylthiophenyl]prop-2-en-1-one,

1-[2-mercapto-4-methyloxyphenyl]-3-[4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[2-mercapto-4-methyloxyphenyl]-3-[4-isopropyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-heptylphenyl]-3-[3-methyl-4-carboxydimethymethyloxyphenyl]prop-2-en-1-one,

1-[4-heptylphenyl]-3-[3-methyl-4-isopropyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

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

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

1-[2-methoxyphenyl]-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,

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

2-(3,5-dimethyl-4-carboxydimethylmethyloxyphenyl)-7-chloro4H-1-benzopyran-4-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,

1-[4-bromophenyl]-3-[3,5-dimethyl-4-carboxy dimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-trifluoromethylphenyl]-3-[3-methyl-4-tertiobutyloxycarbonylmethyloxyphenyl]prop-2-en-1-one,

1-[4-trifluoromethylphenyl]-3-[3-methyl-4-carboxymethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-tertiobutyl-4-tertiobutyloxydimethymethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-tertiobutyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-trifluoromethyl-4-carboxydimethylmethyloxypheny]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-cyclohexyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-cyclohexyl-4-carboxydimethylmethyoxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3-trifluoromethyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1-[4-methylthiophenyl]-3-[3,5-diisopropyl-4-tertiobutyloxycarbonylmethyloxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3,5-diisopropyl-4-carboxymethyloxyphenyl]prop-2-en-1-one,

1-[4-(2-bromoethyloxy)phenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

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

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

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

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

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

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

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

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

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

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

1-[4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]-3-[3,5-ditertiobutyl-4-hydroxyphenyl]prop-2-en-1-one,

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

6. The composition according to claim 1 wherein compound of formula (I) is selected in the group consisting of:

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

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

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

1-[4-trifluoromethylphenyl]-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,

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

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

7. The composition according to claim 1, for the treatment of restenosis, atherosclerosis, type 2 diabetes, obesity, or hypertension.

8. The composition according to claim 1, for the treatment of type 2 diabetes and obesity.

9. A compound selected in the group consisting of:

1-[4-trifluoromethylphenyl]-3-[3-methyl-4-tertiobutyloxycarbonylmethyloxyphenyl]prop-2-en-1-one,

1-[4-trifluoromethylphenyl]-3-[3-methyl-4-carboxymethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-tertiobutyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-tertiobutyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-trifluoromethyl-4-carboxydimethylmethyloxypheny]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-cyclohexyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-bromophenyl]-3-[3-cyclohexyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3-trifluoromethyl-4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]prop-2-en-1-one,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1-[4-methylthiophenyl]-3-[3,5-diisopropyl-4-tertiobutyloxycarbonylmethyloxyphenyl]prop-2-en-1-one,

1-[4-methylthiophenyl]-3-[3,5-diisopropyl-4-carboxymethyloxyphenyl]prop-2-en-1-one,

1-[4-(2-bromoethyloxy)phenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxyphenyl]prop-2-en-1-one,

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

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

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

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

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

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

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

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

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

1-[4-hexylthiophenyl]-3-[3,5-dimethyl-4-carboxydimethylmethyloxypheny]prop-2-en-1-one,

1-[4-tertiobutyloxycarbonyldimethylmethyloxyphenyl]-3-[3,5-ditertiobutyl-4-hydroxyphenyl]prop-2-en-1-one,

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