IP Library Granted Patent US 7,625,914
Granted Patent B2
US 7,625,914 · App. 11/311,449 · Granted Dec 1, 2009

Compounds that modulate PPARγ type receptors and cosmetic/pharmaceutical compositions comprised thereof

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Quick Facts
Patent No.
US 7,625,914
App. No.
11/311,449
Granted
Dec 1, 2009
Kind
B2
Abstract

Novel compounds having the general formula (I) below: are useful in a wide variety of applications in human or veterinary medicine (in dermatology, and also in the fields of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism), or, alternatively are formulated into cosmetic compositions.

Claims (237)

1. A compound having the following structural formula (I):

in which:

R2 is an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical, a heterocyclic radical, a 9-fluorenylmethyl radical or a radical of formula (CH 2 )m(NR5)n(C(O,N)) p R6;

R5, R6, m, n and p are as defined below;

R5 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical or a heterocyclic radical,

R6 is:

an alkyl radical having from 1to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical, a heterocyclic radical,

a radical

or a radical NR′(CH 2 ) v R10;

where R10, R′, R″and v are as defined below;

m has the values 0, 1 or 2;

n and p have the values 0 or 1;

v has the values 1, 2 or 3;

R10 is an alkyl radical having from 1to 12 carbon atoms, an aryl, aralkyl, heteroaryl or heterocyclic radical, a radical NH-CO-R12, a radical NH—CO—O—R12 or C-R12R13 or a radical N-R12R13, wherein R12 and R13 are as defined below;

R′ is a hydrogen atom, an alkyl radical having from 1to 12 carbon atoms, a heteroaryl radical or a heterocyclic radical;

R″ is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, optionally substituted with one or more halogens, a heteroaryl radical, a heterocyclic radical, a radical (CH 2 ) v -R10, or a radical NHR10 or NR10R10;

R12 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical or a heterocyclic radical;

R13 is a hydrogen atom or an alkyl radical having from 1 to 12 carbon atoms;

T is an oxygen or sulfur atom; and

Ar1 and Ar2, which may be identical or different, are each an optionally substituted aromatic radical of one of the formulae:

wherein A is an S or O atom or a radical N-R13, with the proviso that, when Ar1or Ar2 is a

radical, then Ar2 or Ar1 is not a

radical, or an optical or geometrical isomer or salt thereof.

2. A compound as defined by claim 1 , wherein formula (I), Ar1 and Ar2, which may be identical or different, are each one of the unsubstituted radicals:

with the proviso that, when Ar1 or Ar2 is a

radical, then Ar2 or Ar1 is

not a

radical.

3. A compound as defined by claim 1 , in the form of a carboxylic acid salt, an organic amine salt or a salt of an amine function.

4. A compound as defined by claim 3 , in the form of an alkali metal or alkaline-earth metal salt, an amino acid salt, a salt of a halogen atom or an organic acid or nitrate salt.

5. A compound as defined by claim 1 , comprising at least one linear or cyclic, saturated or unsaturated, optionally branched, hydrogen-containing or fluorine-containing alkyl radical having 1 to 12 carbon atoms, which may be interrupted with a hetero atom.

6. A compound as defined by claim 1 , comprising at least one phenyl, biphenyl, cinnamyl or naphthyl radical, which may be mono- or disubstituted with a halogen atom, a CF 3 radical, an alkyl radical having from 1 to 12 carbon atoms, an alkoxy radical having from 1 to 7 carbon atoms, a nitro function, a polyether radical, an aryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl radical optionally protected with an acetyl or benzoyl group or an amino function optionally protected with an acetyl or benzoyl group or optionally substituted with at least one alkyl radical having from 1 to 12 carbon atoms.

7. A compound as defined by claim 1 , comprising at least one benzyl, phenethyl or 2-naphthylmethyl radical, which may be mono- or disubstituted with a halogen atom, a CF 3 radical, an alkyl radical having from 1 to 12 carbon atoms, an alkoxy radical having from 1 to 7 carbon atoms, a nitro function, a polyether radical, an aryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl radical optionally protected with an acetyl or benzoyl group or an amino function optionally protected with an acetyl or benzoyl group or optionally substituted with at least one alkyl radical having from 1 to 12 carbon atoms.

8. A compound as defined by claim 1 , comprising at least one pyridyl, furyl, thienyl, isoxazolyl, oxadiazolyl, oxazolyl, isothiazolyl, quinazolinyl, benzothiadiazolyl, benzimidazolyl, quinoxalyl, indolyl or benzofuryl radical, optionally substituted with at least one halogen, an alkyl radical having from 1 to 12 carbon atoms, an alkoxy radical having from 1 to 7 carbon atoms, an aryl radical, a nitro function, a polyether radical, a heteroaryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl optionally protected with an acetyl or benzoyl group or an amino function optionally protected with an acetyl or benzoyl group or optionally substituted with at least one alkyl radical having from 1 to 12 carbon atoms.

9. A compound as defined by claim 1 , comprising at least one morpholino, piperidino, piperazino, 2-oxo-1-piperidyl or 2-oxo-1-pyrrolidinyl radical, optionally substituted with at least one alkyl radical having from 1 to 12 carbon atoms, an alkoxy radical having from 1 to 7 carbon atoms, an aryl radical, a nitro function, a polyether radical, a heteroaryl radical, a benzoyl radical, an alkyl ester group, a carboxylic acid, a hydroxyl optionally protected with an acetyl or benzoyl group or an amino function optionally protected with an acetyl or benzoyl group or optionally substituted with at least one alkyl radical having from 1 to 12 carbon atoms.

10. A compound as defined by claim 1 , comprising at least one halogen atom selected from the group consisting of a fluorine atom, a chlorine atom and a bromine atom.

11. A compound as defined by claim 1 , selected from the group consisting of:

2(S)-Ethoxy-3-{4-[2-(3-heptyl-1-methylureido)thiazol-4-yl]phenyl}propanoic acid

2(S)-Ethoxy-3-{4-[2-(3-pentyl-1-methylureido)thiazol-5-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{[6-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium chloride,

2(S)-Ethoxy-3-{4-[5-(3-heptyl-1-methylureido)-2-methyl-2H-[1,2 ,4]triazol-3-yl]phenyl}propanoic acid,

2-Ethoxy-3-{6-[3-(3-heptyl-1-methylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{6-[3-(3-heptyl-1-methylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride,

3-{4-[6-(3-Butyl-1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-phenethylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-phenylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-naphthalen-2-ylureido)pyrid-2-yl]phenyl}propanoic acid,

3-{4-[6-(3-Cyclohexyl-1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[3-(3-heptyl-1-methylureido)phenyl]thiazol-2-yl}propanoic acid,

2(S)-Ethoxy-3-{4-[3-(1-methyl-3-pentylureido)phenyl]thiazol-2-yl}propanoic acid,

2(S)-Ethoxy-3-{6-[3-(1-methyl-3-pentylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-[4-(6-{3-[2-(4-fluorophenyl)ethyl]- 1-methylureido}pyrid-2-yl)phenyl]propanoic acid,

2(S)-Ethoxy-3-{4-[8-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[4-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[4-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[2-(1-methyl-3-pentylureido)pyrid-4-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[2-(3-heptyl-1-methylureido)pyrid-4-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[2-(3-heptyl-1-methylureido)pyrimidin-4-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[2-(1-methyl-3-pentylureido)pyrimidin-4-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{5-[3-(3-heptyl-1-methylureido)phenyl]furan-2-yl}propanoic acid,

2(S)-Ethoxy-3-{5-[3-(3-heptyl-1-methylureido)phenyl]thiophen-2-yl}propanoic acid,

2(S)-Ethoxy-3-{2-[3-(3-heptyl-1-methylureido)phenyl]pyrimidin-5-yl}propanoic acid,

2(S)-Ethoxy-3-{8-[3-(3-heptyl-1-methylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{4-[5-(3-heptyl-1-methylureido)thiophen-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[5-(3-heptyl-1-methylureido)furan-2-yl]phenyl}propanoic acid,

3-(6-{3-[3-(4-Dimethylaminophenly)-1-methylureido]phenyl}pyrid-3-yl)-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-[6′-(3-heptyl-1-methylureido)-[2,2′]bipyridyl-5-yl]propanoic acid,

2(S)-Ethoxy-3-{5-[3-(1-methyl-3-pentylureido)phenyl]pyrimidin-2-yl}propanoic acid,

2(S)-Ethoxy-3-{6-[4-fluoro-3-(1-methyl-3-pentylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{2-fluoro-4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[5-(1-methyl-3-pentylureido)thiophen-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[5-(3-heptyl-1-methylureido)thiophen-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-[6′-(1-methyl-3-pentylureido)-[2 ,2′]bipyridyl-5-yl]propanoic acid,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium fumarate,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium maleate,

2(S)-Ethoxy-3-(4-{4-[1-methyl-3-(2-piperidin-1-yl-ethyl)-ureido]-pyridin-2-yl}-phenyl)-propanoic acid,

2(S)-Ethoxy-3-(4-{4-[1-methyl-3-(3-phenyl-propyl)-ureido]-pyridin-2-y}-phenyl)-propanoic acid,

2(S)-Ethoxy-3-(4-{4-[1-methyl-3-(4-phenyl-butyl)-ureido]-pyridin-2-yl}-phenyl)-propanoic acid,

3-{4-[4-(3-Benzo[1,2,5]thiadiazol-4-yl-1-methyl-ureido)-pyridin-2-yl]-phenyl}-2(S)-ethoxy-propanoic acid,

3-(4-{4-[3-(4-Dimethylamino-phenyl)-1-methyl-ureido]-pyridin-2-yl}-phenyl)-2(S)-ethoxy-propanoic acid,

2(S)-Ethoxy-3-[4-(4-{3-[2-( 1H-imidazol-2-yl)-ethyl]-1-methyl-ureido}-pyridin-2-yl)-phenyl]-propanoic acid,

3-(4-{4-[3-(2-Dimethylamino-ethyl)-1-methyl-ureido]-pyridin-2-yl}-phenyl)-2(S)-ethoxy-propanoic acid,

2(S)-Ethoxy-3-{4-[4-( I -methyl-3-naphthalen-2-yl-ureido)-pyridin-2-yl]-phenyl}-propanoic acid,

3-{4-[6-(3-Benzo[1,2,5]thiadiazol-4-yl-1-methyl-ureido)-pyridin-2-yl]-phenyl}-2(S)-ethoxy-propanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(3-phenyl-propyl)-ureido]-pyridin-2-yl}-phenyl)-propanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(2-piperidin-1-yl-ethyl)-ureido]-pyridin-2-yl}-phenyl)-propanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(4-phenyl-butyl)-ureido]-pyridin-2-yl}-phenyl)-propanoic acid,

3-(4-{6-[3-(4-Dimethylamino-phenyl)-1-methyl-ureido]-pyridin-2-yl}-phenyl)-2(S)-ethoxy-propanoic acid,

3-(4-{6-[3-(2-Dimethylamino-ethyl)-1-methyl-u reido]-pyridin-2-yl}-phenyl)-2(S)-ethoxy-propanoic acid,

2(S)-Ethoxy-3-[4-(6-{3-[2-(1H-imidazol-2-yl)-ethyl]-1-methyl-ureido}-pyridin-2-yl)-phenyl]-propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentyl-thioureido)-pyridin-2-yl]-phenyl}-propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-heptyl-thioureido)-pyridin-2-yl]-phenyl}-propanoic acid,

2(S)-Ethoxy-3-{6-[3-(3-heptyl-1-methyl-thioureido)-phenyl]-pyridin-3-yl}-propanoic acid,

2(S)-Ethoxy-3-{4-[4-(3-heptyl-1-methyl-thioureido)-pyridin-2-yl]-phenyl}-propanoic acid,

2(S)-Ethoxy-3-(6-{3-[1-methyl-3-(2-piperidin-1-yl-ethyl)-ureido]-phenyl}-pyridin-3-yl)-propanoic acid,

3-(6-{3-[(2-Benzo[1,2,5]thiadiazol-4-yl-ethyl)-1-methyl-ureido]-phenyl}-pyridin-3-yl)-2(S)-ethoxy-propanoic acid,

2(S)-Ethoxy-3-(6-{3-[1-methyl-3-(3-phenyl-propyl)-ureido]-phenyl}-pyridin-3-yl)-propanoic acid,

3-(6-{3-[3-(4-Dimethylamino-phenyl)-1-methyl-ureido]-phenyl}-pyridin-3-yl)-2(S)-ethoxy-propanoic acid.

12. A compound as defined by claim 1 , having at least one of the following characteristics:

R2 is an alkyl, aryl or heteroaryl radical;

T is an oxygen atom;

at least one of Ar1 and Ar2 is a pyridine, thiazole, pyrimidine, thiophene or triazole radical.

13. A cosmetic composition, comprising a cosmetically effective amount of at least one compound as defined in claim 1 , formulated into a cosmetically/physiologically acceptable support therefor.

14. The cosmetic composition as defined by claim 12 , said at least one compound comprising from 0.001% to 3% by weight thereof.

15. The cosmetic composition as defined by claim 12 , formulated for body or hair hygiene.

16. A pharmaceutical composition, comprising a pharmaceutically effective amount of at least one compound as defined in claim 1 , formulated into a pharmaceutically/physiologically acceptable support therefor.

17. The pharmaceutical composition as defined in claim 16 , said at least one compound comprising from 0.001% to 10% by weight thereof.

18. A compound having either of the following structural formulas:

wherein Ar1 in formula (Ia) is pyridyl, Ar2 in formula (Ib) is pyridyl, the depicted phenyl, Ar1 and Ar2 radicals are each optionally substituted, and R2 and T are as defined below;

R2 is an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical or a radical of formula (CH 2 ) m (NR5) n (C(O,N)) p R6; where R5, R6, m, n and p are as defined below;

R5 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, or an aralkyl radical;

R6 is:

an alkyl radical having from 1 to 12 carbon atoms, an aryl radical or an aralkyl radical,

a radical NR′R″

or a radical NR′(CH 2 ) v R10;

where R10, R′, R″ and v are as defined below;

R10 is an alkyl radical having from 1 to 12 carbon atoms, an aryl or aralkyl radical, a radical NH—CO-R12, a radical NH—CO—O—R12 or C—R12R13 or a radical N—R12R13, wherein R12 and R13 are as defined below;

R′ is a hydrogen atom or an alkyl radical having from 1 to 12 carbon atoms;

R″ is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, optionally substituted with one or more halogens, a radical (CH 2 ) v —R10, or a radical NHR10 or NR10R10;

R12 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, or an aralkyl radical;

R13 is a hydrogen atom or an alkyl radical having from 1 to 12 carbon atoms;

m has the value 0, 1 or 2;

n and p each have the value 0 or 1;

v has the value 1, 2 or 3; and

T is an oxygen or sulfur atom; or an optical or geometrical isomer or salt thereof.

19. The compound of claim 18 wherein

T is an oxygen atom.

20. A compound as defined by claim 18 , selected from the group consisting of:

2(S)-Ethoxy-3-{4-[6-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid, 2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium chloride,

2-Ethoxy-3-{6-[3-(3-heptyl-1-methylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{6-[3-(3-heptyl-1-methylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{4-[6-( 1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride,

3-{4-[6-(3-Butyl-1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-phenethylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride,

2(S)-Ethoxy-3-{4-[6-( 1-methyl-3-phenylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-naphthalen-2-ylureido)pyrid-2-yl]phenyl}propanoic acid,

3-{4-[6-(3-Cyclohexyl-1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{6-[3-(1-methyl-3-pentylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-[4-(6-{3-[2-(4-fluorophenyl)ethyl]-1-methylureido}pyrid-2-yl)phenyl]propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[4-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[4-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[2-(1-methyl-3-pentylureido)pyrid-4-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[2-(3-heptyl-1-methylureido)pyrid-4-yl]phenyl}propanoic acid, 3-(6-{3-[3-(4-Dimethylaminophenyl)-1-methylureido]phenyl}pyrid-3-yl)-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{6-[4-fluoro-3-(1-methyl-3-pentylureido)phenyl]pyrid-3-yl}propanoic acid,

2(S)-Ethoxy-3-{2-fluoro-4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium fumarate,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium maleate, 2(S)-Ethoxy-3-(4-{4-[1-methyl-3-(3-phenylpropyl)ureido]pyridin-2-yl}phenyl)propanoic acid,

2(S)-Ethoxy-3-(4-{4-[1-methyl-3-(4-phenylbutyl)ureido]pyridin-2-yl}phenyl)propanoic acid,

3-(4-{4-[3-(4-Dimethylamino-phenyl)-1-methyl-ureido]pyridin-2-yl}phenyl)-2(S)-ethoxy-propanoic acid,

3-(4-{4-[3-(2-Dimethylaminoethyl)-1-methylureido]pyridin-2-yl}phenyl)-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[4-(1-methyl-3-naphthalen-2-ylureido)pyridin-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(3-phenylpropyl)ureido]pyridin-2-yl}phenyl)propanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(4-phenylbutyl)ureido]pyridin-2-yl}phenyl)propanoic acid,

3-(4-{6-[3-(4-Dimethylaminophenyl)-1-methylureido]pyridin-2-yl}phenyl)-2(S)-ethoxypropanoic acid,

3-(4-{6-[3-(2-Dimethylaminoethyl)-1-methylureido]pyridin-2-yl}phenyl)-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentylthioureido)pyridin-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[6-( 1-methyl-3-heptylthioureido)pyridin-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{4-[4-(3-heptyl-1-methylthioureido)pyridin-2-yl]phenyl}propanoic acid, and

3-(6-{3-[3-(2-Benzo[1,2,5]thiadiazol-4-ylethyl)-1-methylureido]phenyl}pyridin-3-yl)-2(S)-ethoxypropanoic acid.

21. A compound having the following structural formula:

wherein the depicted phenyl and pyridyl radicals are each optionally substituted, and R2 and T are as defined below;

R2 is an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical or a radical of formula (CH 2 ) m (NR5) n (C(O,N)) p R6 where R5,R6, m, n and p are as defined below;

R5 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical or an aralkyl radical;

R6 is:

an alkyl radical having from 1 to 12 carbon atoms, an aryl radical or an aralkyl radical,

a radical

or a radical NR′(CH 2 ) v R10;

where R10, R′, R″and v are as defined below;

R1 is an alkyl radical having from 1 to 12 carbon atoms, an aryl or aralkyl radical, a radical NH—CO—R 12, a radical NH—CO—O—R12 or C—R12R13 or a radical N—R12R13, wherein R12 and R13 are as defined below;

R′ is a hydrogen atom or an alkyl radical having from 1 to 12 carbon atoms;

R″ is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, optionally substituted with one or more halogens, a heteroaryl radical, a heterocyclic radical, a radical (CH 2 )v-R10, or a radical NHR10 or NR10R10;

R12 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical or a heterocyclic radical;

R13 is a hydrogen atom or an alkyl radical having from 1 to 12 carbon atoms;

m has the value 0, 1 or 2;

n and p each have the value 0or 1;

v has the value 1,2 or 3; and

T is an oxygen or sulfur atom; or an optical or geometrical isomer or salt thereof.

22. The compound of claim 21 wherein

T is an oxygen atom.

23. A compound as defined by claim 21 , selected from the group consisting of:

2(S)-Ethoxy-3-{4-[8-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium chloride,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride,

3-{4-[6-(3-Butyl-1-methylureido)pyrid-2-yl]pheny}-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-phenethylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-phenylureido)pyrid-2-yl]pheny}propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-naphthalen-2-ylureido)pyrid-2-yl]phenyl}propanoic acid,

3-{4-[6-(3-Cyclohexyl- 1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-[4-(6-{3-[2-(4-fluorophenyl)ethyl]-1-methylureido}pyrid-2-yl)phenyl]propanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2(S)-Ethoxy-3-{2-fluoro-4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium fumarate,

2-[4-(2-Carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium maleate,

2(S)-Isopropoxy-3-{4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid,

3-{4-[6-(3-Pentyl-1-methylureido)pyrid-2-yl]phenyl}-2-methylpropanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(3-phenylpropyl)ureido]pyridin-2-yl}phenyl)propanoic acid,

2(S)-Ethoxy-3-(4-{6-[1-methyl-3-(4-phenylbutyl)ureido]pyridin-2-yl}phenyl)propanoic acid,

3-(4-{6-[3-(4-Dimethylamino-phenyl)-1-methylureido]-pyridin-2-yl}phenyl)-2(S)-ethoxypropanoic acid,

3-(4-{6-[3-(2-Dimethylaminoethyl)-1-methylureido]pyridin-2-yl}phenyl)-2(S)-ethoxypropanoic acid,

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-pentylthioureido)pyridin-2-yl]phenyl}propanoic acid, and

2(S)-Ethoxy-3-{4-[6-(1-methyl-3-heptylthioureido)pyridin-2-yl]-phenyl}propanoic acid.

24. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[6-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid.

25. The compound as defined by claim 1 , which is 2-[4-(2-carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium chloride.

26. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{6-[3-(3-heptyl-1-methylureido)phenyl]pyrid-3-yl}propanoic acid.

27. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[6-(1-methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride.

28. The compound as defined by claim 1 , which is 3-{4-[6-(3-butyl-1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid.

29. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[6-(1-methyl-3-phenethylureido)pyrid-2-yl]phenyl}propanoic acid hydrochloride.

30. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[6-( 1-methyl-3-phenylureido)pyrid-2-yl]phenyl}propanoic acid.

31. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[6-(1-methyl-3-naphthalen-2-ylureido)pyrid-2-yl]phenyl}propanoic acid.

32. The compound as defined by claim 1 , which is 3-{4-[6-(3-cyclohexyl-1-methylureido)pyrid-2-yl]phenyl}-2(S)-ethoxypropanoic acid.

33. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[6-(1methyl-3-pentylureido)pyrid-2-yl]phenyl}propanoic acid.

34. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[4-(3-heptyl-1-methylureido)pyrid-2-yl]phenyl}propanoic acid.

35. The compound as defined by claim 1 , which is 2(S)-ethoxy-3-{4-[4-(1-methyl-3 pentylureido)pyrid-2-yl]phenyl}propanoic acid.

36. The compound as defined by claim 1 , which is 2-[4-(2-carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium fumarate.

37. The compound as defined by claim 1 , which is 2-[4-(2-carboxy-2(S)-ethoxyethyl)phenyl]-6-(3-heptyl-1-methylureido)pyridinium maleate.

38. A compound having the following structural formula (I):

in which:

R2 is an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical or a radical of formula (CH 2 ) m (NR5) n (C(O,N)) p R6

R5,R6, m, n and p are as defined below;

R5 is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical or a heterocyclic radical;

R6 is:

an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, a heteroaryl radical, a heterocyclic radical, or

a radical

wherein R′ and R″ are as defined below;

m has the values 0, 1 or 2;

n and p have the values 0 or 1;

R′ is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, a heteroaryl radical or a heterocyclic radical;

R″ is a hydrogen atom, an alkyl radical having from 1 to 12 carbon atoms, an aryl radical, an aralkyl radical, optionally substituted with one or more halogens, a heteroaryl radical or a heterocyclic radical;

R13 is a hydrogen atom or an alkyl radical having from 1 to 12 carbon atoms;

T is an oxygen or sulfur atom; and

Ar1 and Ar2, which may be identical or different, are each an optionally substituted aromatic radical of one of the formulae:

wherein A is an S or O atom or a radical N—R13, with the proviso that, when Ar1 or Ar2 is a

radical, then Ar2 or Ar1 is not a

radical, or an optical or geometrical isomer or salt thereof.

Assignments (2)
CHANGE OF NAME AND ADDRESS Recorded Sep 6, 2007
From: GALDERMA RESEARCH & DEVELOPMENT, S.N.C.
To: GALDERMA RESEARCH & DEVELOPMENT
Reel/Frame 019795/0626 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 16, 2006
From: CLARY, LAURENCE; THOREAU, ETIENNE; RIVIER, MICHEL; AUBERT, JEROME; CHANTALAT, LAURENT; VOEGEL, JOHANNES
To: GALDERMA RESEARCH & DEVELOPMENT, S.N.C.
Reel/Frame 017343/0988 →