US 2014/0371197 A1Published application

4-(azacycloalkyl)benzene-1,3-diol compounds as tyrosinase inhibitors, process for the preparation thereof and use thereof in human medicine and in cosmetics

AssigneeGalderma Research & Development

InventorsJean-Guy BOITEAU, Karine BOUQUET, Sandrine Talano, Corinne MILLOIS BARBUIS

Life of this patent

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Abstract

4-(Azacycloalkyl)benzene-1,3-diol compounds are described corresponding to general formula (I) below: Also described, are compositions including the same, processes for preparation thereof and uses thereof in pharmaceutical or cosmetic compositions to treat pigmentary disorders.

Claims23

Dependent claims

A pharmaceutical or cosmetic composition comprising a compound of formula (I) below:

in which:
R1 represents:
a C1-C5 alkyl radical,
a C3-C5 cycloalkyl radical,
an aryl radical,
a substituted aryl radical,
an aralkyl radical,
a C1-C5 alkoxy radical,
an amino radical corresponding to structure (a):
in which R2 represents:
a hydrogen,
a C1-C5 alkyl radical,
a C3-C6 cycloalkyl radical,
an aryl radical,
a substituted aryl radical,
a pyridyl radical,
an aralkyl radical,
a radical corresponding to structure (b):
in which p can have the value 1 or 2,
a radical corresponding to structure (c):
in which R4 represents:
a carboxymethyl —COOCH3 or carboxyethyl —COOEt radical,
a C1-C3 alkyl radical,
a hydrogen,
and R5 represents:
a substituted or unsubstituted aryl radical,
a C3-C6 cycloalkyl radical,
a pyridyl,
and R3 represents:
a hydrogen,
a C1-C5 alkyl radical;
or R1 may also represent a radical corresponding to formula (d):
in which R6 represents:
a hydrogen,
a C1-C5 alkyl radical,
a C3-C6 cycloalkyl radical,
an aryl radical,
a substituted aryl radical,
a pyridyl radical,
an aralkyl radical,
R7 represents:
a hydrogen,
a C1-C5 alkyl radical,
and R8 represents:
a hydrogen,
a hydroxyl,
an amino radical,
a C1-C5 alkoxy radical:
Y represents a hydrogen or a fluorine, and
m and n can have the value 0, 1 or 2,
or a salt of a compound of formula (I), or an enantiomer form thereof;
and a pharmaceutically acceptable or cosmetically acceptable carrier.

49 more elements

A pharmaceutical or cosmetic composition comprising a compound selected from the group consisting of:

1:
3-(2,4-dihydroxyphenyl)azetidine-1-carboxylic acid tert-butyl ester;
2:
[3-(2,4-dihydroxyphenyl)azetidin-1-yl]phenylmethanone;
3:
3-(2,4-dihydroxyphenyl)azetidine-1-carboxylic acid pentylamide;
4:
3-(2,4-dihydroxyphenyl)pyrrolidine-1-carboxylic acid tert-butyl ester;
5:
3-(2,4-dihydroxyphenyl)pyrrolidine-1-carboxylic acid isobutyl ester;
6:
3-(2,4-dihydroxyphenyl)pyrrolidine-1-carboxylic acid cyclohexylamide;
7:
3-(2,4-dihydroxyphenyl)pyrrolidine-1-carboxylic acid phenylamide;
8:
3-(2,4-dihydroxyphenyl)pyrrolidine-1-carboxylic acid (4-fluorophenyl)amide;
9:
3-(2,4-dihydroxyphenyl)pyrrolidine-1-carboxylic acid (4-trifluoromethylphenyl)amide;
10:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ethyl ester;
11:
[4-(2,4-dihydroxyphenyl)piperidin-1-yl]phenylmethanone;
12:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid butylamide;
13:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid propylamide;
14:
1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]butan-1-one;
15:
1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-methylpropan-1-one;
16:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid phenylamide;
17:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (4-fluorophenyl)amide;
18:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid p-tolylamide;
19:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid phenethylamide;
20:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (3-fluorophenyl)amide;
21:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((R)-1-phenylethyl)amide;
22:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid methylphenylamide;
23:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid pyridin-2-ylamide;
24:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-phenylethyl)amide;
25:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-phenylpropyl)amide;
26:
(R)-2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-3-phenylpropan-1-one;
27:
1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-3-phenylpropan-1-one;
28:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 2-fluorobenzylamide;
29:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 3-fluorobenzylamide;
30:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 4-fluorobenzylamide;
31:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid benzylamide;
32:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 2-methylbenzylamide;
33:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 3-methylbenzylamide;
34:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 4-methylbenzylamide;
35:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 2-methoxybenzylamide;
36:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 3-methoxybenzylamide;
37:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid 4-methoxybenzylamide;
38:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-p-tolylethyl)amide;
39:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid [(S)-1-(4-fluorophenyl)ethyl]amide;
40:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (S)-indan-1-ylamide;
41:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-naphthalen-1-ylethyl)amide;
42:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-naphthalen-2-ylethyl)amide;
43:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid [(S)-1-(4-methoxyphenyl)ethyl]amide;
44:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid [(S)-1-(3-meth oxyphenyl)ethyl]amide;
45:
(S)-2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-3-phenylpropan-1-one;
46:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-phenylethyl)amide;
47:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylethanone;
48:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylethanone;
49:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-3-phenylpropan-1-one;
50:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-3-phenylpropan-1-one;
51:
(R)-2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-(4-fluorophenyl)ethanone;
52:
(R)-2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-phenylethanone;
53:
(S)-2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-phenylethanone;
54:
(R)-2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-(4-trifluoromethyl phenyl)ethanone;
55:
2-amino-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-phenylbutan-1-one;
56:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-methoxy-2-phenylethanone;
57:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-cyclohexylethyl)amide;
58:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (1,2,3,4-tetrahydronaphthalen-1-yl)amide;
59:
(R)-{[4-(2,4-dihydroxyphenyl)piperidine-1-carbonyl]amino}phenylacetic acid methyl ester,
60:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (pyridin-3-ylmethyl)amide;
61:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (pyridin-4-ylmethyl)amide;
62:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid benzylamide;
63:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid butylamide;
64:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (3-fluorophenyl)amide;
65:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid phenethylamide;
66:
(R)-{[4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carbonyl]amino}phenylacetic acid methyl ester;
67:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (S)-indan-1-ylamide;
68:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid [(S)-1-(4-methoxyphenyl)ethyl]amide;
69:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((S)-1-cyclohexylethyl)amide;
70:
(R)-1-[4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylethanone;
71:
(S)-1-[4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylethanone;
72:
(R)-2-amino-1-[4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-yl]-2-phenylethanone;
73:
(S)-2-amino-1-[4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-yl]-2-phenylethanone;
74:
(R)-1-[4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylpropan-1-one;
75:
(S)-1-[4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylpropan-1-one;
76:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylpropan-1-one;
77:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylpropan-1-one;
78:
(R)-{[4-(2,4-dihydroxyphenyl)piperidine-1-carbonyl]amino}-(4-fluorophenyl)acetic acid methyl ester,
79:
(S)-{[4-(2,4-dihydroxyphenyl)piperidine-1-carbonyl]amino}-(4-fluorophenyl)acetic acid methyl ester;
80:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-methyl-3-phenylpropan-1-one;
81:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-methyl-3-phenylpropan-1-one;
82:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidin-1-carboxylic acid (pyridin-3-ylmethyl)amide;
83:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (pyridin-4-ylmethyl)amide;
84:
(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid ((R)-1-phenylethyl)amide;
85:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylbutan-1-one;
86:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-phenylbutan-1-one;
87:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-(4-fluorophenyl)-2-hydroxyethanone;
88:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-(4-fluorophenyl)-2-hydroxyethanone;
89:
(S)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-(3-methoxyphenyl)ethanone;
90:
(R)-1-[4-(2,4-dihydroxyphenyl)piperidin-1-yl]-2-hydroxy-2-(3-methoxyphenyl)ethanone;
91:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid cyclohexylmethylamide;
92:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid cyclohexylmethylamide;
93:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2-ethylbutyl)amide;
94:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2-ethylbutyl)amide;
95:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid cyclopentylmethylamide;
96:
4-(5-fluoro-2,4-dihydroxyphenyl)piperidine-1-carboxylic acid cyclopentylmethylamide;
97:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (6-methylpyridin-3-ylmethyl)amide;
98:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (4-methylpyridin-3-ylmethyl)amide;
99:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (5-methylpyridin-3-ylmethyl)amide;
100:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2-methylpyridin-3-ylmethyl)amide;
101:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2,6-dimethylpyridin-4-ylmethyl)amide;
102:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2-pyridin-2-ylethyl)amide;
103:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2-pyridin-3-ylethyl)amide;
and
104:
4-(2,4-dihydroxyphenyl)piperidine-1-carboxylic acid (2-pyridin-4-ylethyl)amide;
or a salt or an enantiomer thereof;
and a pharmaceutically acceptable or cosmetically acceptable carrier.

208 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/469,199Filed 29 Aug 2014
Priority: FR 08582072 Dec 2008
Published: 18 Dec 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

A61P 17/00
Drugs for dermatological disorders
C07D 211/26
With substituted hydrocarbon radicals attached to ring carbon atoms: with hydrocarbon radicals, substituted by nitrogen atoms
A61K 9/06
Medicinal preparations characterised by special physical form: ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
A61P 17/02
Drugs for dermatological disorders: for treating wounds, ulcers, burns, scars, keloids, or the like

Family

Application61/193,460Us provisional application · filed 2 Dec 2008
Application13/131,363Continuation · filed 12 Sep 2011
Application13/611,546Continuation · filed 12 Sep 2012
Application14/200,954Continuation · filed 7 Mar 2014
Application14/469,199Continuation
US 2011/0311466 A1Published application
US 2013/0023516 A1Published application
US 2014/0187532 A1Published application
US 8,299,259 B2Related patent
US 8,697,726 B2Related patent
US 8,993,596 B2Related patent
US 2014/0371197 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

14/469,199Filed 29 Aug 2014

Priority

FR 08582072 Dec 2008

Published

18 Dec 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

A61P 17/00
Drugs for dermatological disorders
C07D 211/26
With substituted hydrocarbon radicals attached to ring carbon atoms: with hydrocarbon radicals, substituted by nitrogen atoms
A61K 9/06
Medicinal preparations characterised by special physical form: ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
A61P 17/02
Drugs for dermatological disorders: for treating wounds, ulcers, burns, scars, keloids, or the like

Family

Application61/193,460Us provisional application · filed 2 Dec 2008

Application13/131,363Continuation · filed 12 Sep 2011

Application13/611,546Continuation · filed 12 Sep 2012

Application14/200,954Continuation · filed 7 Mar 2014

Application14/469,199Continuation

US 2011/0311466 A1Published application

US 2013/0023516 A1Published application

US 2014/0187532 A1Published application

US 8,299,259 B2Related patent

US 8,697,726 B2Related patent

US 8,993,596 B2Related patent

US 2014/0371197 A1This patent

From the US filing history. Foreign family members aren’t listed.