Benzofuran-2-sulfonamides derivatives as chemokine receptor modulators

• US 8,927,544 B2
• Filed: 03/01/2013
• Issued: 01/06/2015
• Est. Priority Date: 03/01/2012
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Yuan, Haiqing, Beard, Richard L., Liu, Xiaoxia, Donello, John E., Viswanath, Veena, Garst, Michael E.
• Primary Examiner(s): Rao, Savitha
• Assistant Examiner(s): BROWN-PETTIGREW, ANGELA C
• Application Number:
  US13/782,159
• Publication Number:
  US 20130231338A1
• Time in Patent Office: 676 Days
• Field of Search: 514/233.5, 514/320, 514/337, 514/470, 544/153, 546/196, 546/284.1, 549/466
• US Class Current: 514/233.5
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07D 307/78 Benzo [b] furans; Hydrogenated benzo [b] furans
• CPC Class Codes: C07D 307/82 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

The present invention relates to benzofuran-2-sulfonamide derivatives with the following formula:

• • or pharmaceutically acceptable salts thereof. The derivatives are useful as modulators of chemokine receptors.

Claims

1. A compound represented by Formula I, its individual enantiomers, individual diastereoisomers, individual tautomers or a pharmaceutically acceptable salt thereof:

2. A compound according to claim 1 wherein:

R¹ is hydrogen, halogen or methyl

R² is hydrogen, halogen or methyl

R³ is hydrogen, halogen or methyl

R⁴ is hydrogen, halogen or methyl

R⁵ is hydrogen, halogen or methyl

R⁶ is hydrogen, halogen or methyl

R⁷ is halogen

R⁸ is hydrogen, halogen or methyl

R⁹ is O;

a is 1;

R¹¹ is CN, substituted or unsubstituted C_1-6 alkyl, CF₃, OR¹², NR¹³R¹⁴, substituted or unsubstituted C_6-10 aryl, substituted or unsubstituted heterocycle, substituted or unsubstituted C_3-8 cycloalkyl, substituted or unsubstituted C_2-6 alkyne, substituted or unsubstituted C_2-6 alkene or COR¹⁵;

R¹² is hydrogen or substituted or unsubstituted C_1-6 alkyl;

R¹³ is hydrogen or substituted or unsubstituted C_1-6 alkyl or can form an optionally substituted heterocycle with R¹⁴;

R¹⁴ is hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted heterocycle or substituted or unsubstituted C_6-10 aryl or can form an optionally substituted heterocycle with R¹³;

R¹⁵ is hydrogen, hydroxyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C_6-10 aryl or substituted or unsubstituted C_1-6 alkyl;

X is CR¹⁷;

R¹⁷ is hydrogen; and

R¹⁸ is hydrogen.

3. A compound according to claim 2 selected from:

N-(5-chloro-2-methoxyphenyl)-1-benzofuran-2-sulfonamide;

N-[5-chloro-2-(trifluoromethoxy)phenyl]-1-benzofuran-2-sulfonamide;

N-(5-chloro-2-ethoxyphenyl)-1-benzofuran-2-sulfonamide;

N-{5-chloro-2-[(2-methylpyridin-3-yl)oxy]phenyl}-1-benzofuran-2-sulfonamide;

methyl 2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}benzoate;

2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}benzoic acid;

N-[2-(benzyloxy)-5-chlorophenyl]-1-benzofuran-2-sulfonamide;

methyl 2-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoate;

2-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoic acid;

methyl 3-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoate;

3-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoic acid;

methyl 2-(2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}ethyl)benzoate; and

2-(2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}ethyl)benzoic acid.

4. A compound according to claim 1 wherein:

R¹ is hydrogen, halogen or methyl

R² is hydrogen, halogen or methyl

R³ is hydrogen, halogen or methyl

R⁴ is hydrogen, halogen or methyl

R⁵ is hydrogen, halogen or methyl

R⁶ is hydrogen, halogen or methyl

R⁷ is halogen;

R⁸ is hydrogen, halogen or methyl

R⁹ is C(O);

a is 1;

R¹¹ is CN, substituted or unsubstituted C_1-6 alkyl, CF₃, OR¹², NR¹³R¹⁴, substituted or unsubstituted C_6-10 aryl, substituted or unsubstituted heterocycle, substituted or unsubstituted C_3-8 cycloalkyl, substituted or unsubstituted C_2-6 alkyne, substituted or unsubstituted C_2-6 alkene or COR¹⁵;

R¹² is hydrogen or substituted or unsubstituted C_1-6 alkyl;

R¹³ is hydrogen or substituted or unsubstituted C_1-6 alkyl or can form an optionally substituted heterocycle with R¹⁴;

R¹⁴ is hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted heterocycle or substituted or unsubstituted C_6-10 aryl or can form an optionally substituted heterocycle with R¹³;

R¹⁵ is hydrogen, hydroxyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C_6-10 aryl or substituted or unsubstituted C_1-6 alkyl;

X is CR¹⁷;

R¹⁷ is hydrogen; and

R¹⁸ is hydrogen.

5. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable adjuvant, diluent or carrier.

6. A pharmaceutical composition according to claim 5 wherein the compound is selected from:

N-(5-chloro-2-methoxyphenyl)-1-benzofuran-2-sulfonamide;

N-[5-chloro-2-(trifluoromethoxy)phenyl]-1-benzofuran-2-sulfonamide;

N-(5-chloro-2-ethoxyphenyl)-1-benzofuran-2-sulfonamide;

N-{5-chloro-2-[(2-methylpyridin-3-yl)oxy]phenyl}-1-benzofuran-2-sulfonamide;

methyl 2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}benzoate;

2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}benzoic acid;

N-[2-(benzyloxy)-5-chlorophenyl]-1-benzofuran-2-sulfonamide;

methyl 2-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoate;

2-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoic acid;

methyl 3-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoate;

3-({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}methyl)benzoic acid;

methyl 2-(2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}ethyl)benzoate; and

2-(2-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenoxy}ethyl)benzoic acid.