Sulfur derivatives as chemokine receptor modulators

Patent metadata

Field	Value
Publication number	US-9328067-B2
Application number	US-201313795850-A
Country	US
Kind code	B2
Filing date	Mar 12, 2013
Priority date	Dec 16, 2010
Publication date	May 3, 2016
Grant date	May 3, 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 methyl-4-benzoic acid, tert-butyl 2-(4-methylbenzamido)acetate, 2-(4-methylbenzamido)acetic acid, methyl-3-methylbenzoate, 4-methyl-N-(2-(pyrrolidin-1-yl)ethyl)benzamide, 4-methyl-N-(2-(1-oxipyrrolidin-1-yl)ethyl)benzamide, 3-methyl-N-(2-(pyrrolidin-1-yl)ethyl)benzamide, methyl-2-methylbenzoate, methyl-2-benzoic acid, N,N-diethylpropanamide, 3-oxo-3-(pyrrolidin-1-yl)propyl, methyl-2-benzamide, methyl-2-N,N-dimethylbenzamide, methyl-2-N-ethylbenzamide, methylpropanoate, propanoic acid or N-ethyl-N-methylpropanamide;
R 5 is —S—, —S(O)—, or —S(O) 2 —;
R 6 is 4-chloro-3-trifluoromethylphenyl;
R 17 is H;
R 18 is H;
R 7 is chlorine, methyl, or fluorine;
R 8 is H.

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

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

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

5. A compound selected from the group consisting of:
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N-ethylbenzamide;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N,N-dimethylbenzamide;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzamide;
4-chloro-N-(5-chloro-2-{[3-oxo-3-(pyrrolidin-1-yl)propyl]sulfonyl}phenyl)-3-(trifluoromethyl)benzenesulfonamide;
4-chloro-N-(5-chloro-2-{[3-oxo-3-(pyrrolidin-1-yl)propyl]sulfinyl}phenyl)-3-(trifluoromethyl)benzenesulfonamide;
4-chloro-N-(5-chloro-2-{[3-oxo-3-(pyrrolidin-1-yl)propyl]sulfanyl}phenyl)-3-(trifluoromethyl)benzenesulfonamide;
3-{[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}-N,N-diethylpropanamide;
3-{[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}-N,N-diethylpropanamide;
3-{[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}-N,N-diethylpropanamide;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)benzoic acid;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)benzoic acid;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzoic acid;
methyl 2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)benzoate;
methyl 2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)benzoate;
methyl 2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzoate;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)-N-[2-(1-oxidopyrrolidin-1-yl)ethyl]benzamide;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)-N-[2-(1-oxidopyrrolidin-1-yl)ethyl]benzamide;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)-N-[2-(1-oxidopyrrolidin-1-yl)ethyl]benzamide;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N-[2-(1-oxidopyrrolidin-1-yl)ethyl]benzamide;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)-N-[2-(1-oxidopyrrolidin-1-yl)ethyl]benzamide;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)benzoic acid;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N-[2-(pyrrolidin-1-yl)ethyl]benzamide
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N-[2-(pyrrolidin-1-yl)ethyl]benzamide;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)benzoic acid;
3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzoic acid;
methyl 3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)benzoate;
methyl 3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)benzoate;
methyl 3-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzoate;
({[4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)phenyl]carbonyl}amino)acetic acid;
({[4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)phenyl]carbonyl}amino)acetic acid;
({[4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)phenyl]carbonyl}amino)acetic acid;
tert-butyl({[4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)phenyl]carbonyl}amino) acetate;
tert-butyl({[4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)phenyl]carbonyl}amino) acetate;
tert-butyl({[4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)phenyl]carbonyl}amino) acetate;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}methyl)benzoic acid;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}methyl)benzoic acid;
4-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzoic acid; and
Methyl 4-(((4-chloro-2-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)phenyl)thio)methyl)benzoate; or their enantiomers, diastereoisomers, hydrates, solvates, crystal forms and individual isomers, tautomers or a pharmaceutically acceptable salt thereof.

6. 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.

7. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound selected from the group consisting of:
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N-ethylbenzamide;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)-N,N-dimethylbenzamide;
2-({[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}methyl)benzamide;
4-chloro-N-(5-chloro-2-{[3-oxo-3-(pyrrolidin-1-yl)propyl]sulfonyl}phenyl)-3-(trifluoromethyl)benzenesulfonamide;
4-chloro-N-(5-chloro-2-{[3-oxo-3-(pyrrolidin-1-yl)propyl]sulfinyl}phenyl)-3-(trifluoromethyl)benzenesulfonamide;
4-chloro-N-(5-chloro-2-{[3-oxo-3-(pyrrolidin-1-yl)propyl]sulfanyl}phenyl)-3-(trifluoromethyl)benzenesulfonamide;
3-{[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfonyl}-N,N-diethylpropanamide;
3-{[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfinyl}-N,N-diethylpropanamide;
3-{[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]sulfanyl}-N,N-dieth

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

• A61P29/00

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

• A61P31/00

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

• A61P27/02

  Ophthalmic agents · CPC title

• C07C323/49

  to sulfur atoms · CPC title