Sulfur derivatives as chemokine receptor modulators

Patent metadata

Field	Value
Publication number	US-9371278-B2
Application number	US-201414250169-A
Country	US
Kind code	B2
Filing date	Apr 10, 2014
Priority date	Dec 16, 2010
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

The present invention relates to novel sulfur derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.

First claim

What is claimed is:

1. A compound having Formula I, its enantiomers, diastereoisomers, hydrates, solvates, crystal forms and individual isomers, tautomers or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is H;
R 2 is C 1-6 alkyl substituted with ester groups or amide groups or carboxylic acid groups;
R 5 is —S—, —S(O)—, or —S(O) 2 —;
R 6 is 4-chloro-2-fluorophenyl;
R 17 is H, substituted or unsubstituted C 1-6 alkyl, halogen, substituted or unsubstituted —OC 1-6 alkyl, CN, C(O)R 19 , NR 20 R 21 or hydroxyl;
R 18 is H, substituted or unsubstituted C 1-6 alkyl, halogen, substituted or unsubstituted —OC 1-6 alkyl, CN, C(O)R 22 , NR 23 R 24 or hydroxyl;
R 7 is H, halogen, CN, substituted or unsubstituted —OC 1-6 alkyl, substituted or unsubstituted C 1-6 alkyl or is substituted or unsubstituted C 3-8 cycloalkyl;
R 8 is H, substituted or unsubstituted C 1-6 alkyl, halogen, substituted or unsubstituted —OC 1-6 alkyl, CN or hydroxyl;
R 19 is H, OH or substituted or unsubstituted C 1-6 alkyl
R 20 is H or substituted or unsubstituted C 1-6 alkyl;
R 21 is H or substituted or unsubstituted C 1-6 alkyl;
R 22 is H, OH or substituted or unsubstituted C 1-6 alkyl
R 23 is H or substituted or unsubstituted C 1-6 alkyl; and
R 24 is H or substituted or unsubstituted C 1-6 alkyl.

2. The compound according to claim 1 , wherein:
R 5 is S.

3. The compound according to claim 1 , wherein:
R 5 is —S(O)—.

4. The compound according to claim 1 , wherein:
R 5 is —S(O) 2 —.

5. The compound according to claim 1 , wherein:
R 1 is H;
R 2 is C 1-6 alkyl substituted with ester groups or amide groups or carboxylic acid groups;
R 5 is —S—, —S(O)—, or —S(O) 2 —;
R 6 is 4-chloro-2-fluorophenyl;
R 17 is H, substituted or unsubstituted C 1-6 alkyl or halogen;
R 18 is H, substituted or unsubstituted C 1-6 alkyl or halogen;
R 7 is H, halogen, CN, —OC 1-6 alkyl, substituted or unsubstituted C 1-6 alkyl or substituted or unsubstituted C 3-8 cycloalkyl; and
R 8 is H, substituted or unsubstituted C 1-6 alkyl, CN or halogen.

6. The compound according to claim 5 , wherein:
R 1 is H;
R 2 is C 1-6 alkyl substituted with ester groups or amide groups or carboxylic acid groups;
R 5 is —S—, —S(O)—, or —S(O) 2 —;
R 6 is 4-chloro-2-fluorophenyl;
R 17 is H;
R 7 is H;
R 7 is H, halogen or C 1-6 alkyl; and
R 8 is H.

7. The compound according to claim 6 , wherein:
R 1 is H;
R 2 is N,N-diethylpropanamide, methylpropanoate, propanoic acid or N-ethyl-N-methylpropanamide;
R 5 is —S(O) 2 —, S or —S(O)—;
R 6 is 4-chloro-2-fluorophenyl;
R 7 is chlorine, methyl or fluorine;
R 17 is H;
R 18 is H; and
R 8 is H.

8. The compound according to claim 7 , wherein:
R 5 is —S.

9. The compound according to claim 7 , wherein:
R 5 is —S(O).

10. The compound according to claim 7 , wherein:
R 5 is —S(O) 2 —.

11. The compound according to claim 1 , selected from:
methyl 3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfanyl]propanoate;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfanyl]propanoic acid;
methyl 3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfonyl]propanoate;
methyl 3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfinyl]propanoate;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfonyl]propanoic acid;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfinyl]propanoic acid;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfanyl]-N-ethyl-N-methylpropanamide;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfinyl]-N-ethyl-N-methylpropanamide; and
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfonyl]-N-ethyl-N-methylpropanamide.

12. 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.

13. The pharmaceutical composition according to claim 12 wherein the compound is selected from:
methyl 3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfanyl]propanoate;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfanyl]propanoic acid;
methyl 3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfonyl]propanoate;
methyl 3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfinyl]propanoate;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfonyl]propanoic acid;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfinyl]propanoic acid;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfanyl]-N-ethyl-N-methylpropanamide;
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfinyl]-N-ethyl-N-methylpropanamide; and
3-[(4-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)sulfonyl]-N-ethyl-N-methylpropanamide.

Assignees

• Allergan Inc

Inventors

• Yuan Haiqing
• Beard Richard L
• Liu Xiaoxia
• Donello John E
• Viswanath Veena
• Garst Michael E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07C323/67

  containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton · CPC title