Aryl sulfonamides

Patent metadata

Field	Value
Publication number	US-9890148-B2
Application number	US-201414551438-A
Country	US
Kind code	B2
Filing date	Nov 24, 2014
Priority date	Nov 18, 2002
Publication date	Feb 13, 2018
Grant date	Feb 13, 2018

Abstract

Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.

First claim

What is claimed is:

1. A compound of the formula (I), or a salt thereof:

where X represents from 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO 2 , —OH, —OR 1 , —C(O)R 1 , —CO 2 R 1 , —O(CO)R 1 , —C(O)NR 1 R 2 , —OC(O)NR 1 R 2 , —SR 1 , —SOR 1 , —SO 2 R 1 , —SO 2 NR 1 R 2 , —NR 1 R 2 , —NR 1 C(O)R 2 , —NR 1 C(O) 2 R 2 , —NR 1 SO 2 R 2 , —NR 1 (CO)NR 2 R 3 , unsubstituted C 1-8 alkyl, unsubstituted C 2-8 alkenyl, and unsubstituted C 2-8 alkynyl,
R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, unsubstituted C 1-6 haloalkyl, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl,
or two of R 1 , R 2 and R 3 together with the atom(s) to which they are attached, may form an unsubstituted 5-, 6- or 7-membered ring;
Y represents from 1 to 3 substituents, each independently selected from the group consisting of halogen, —CN, —NO 2 , —OH, —OR 4 , —C(O)R 4 , —CO 2 R 4 , —SR 4 , —SOR 4 , —SO 2 R 4 , and unsubstituted C 1-4 alkyl;
R 4 is selected from the group consisting of hydrogen, unsubstituted C 1-6 haloalkyl, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; L is —C(O)—, —S—, —SO— or —S(O) 2 ; and Z is an unsubstituted or substituted heteroaryl selected from indazolyl, pyrimidinyl, pyridazinyl, and pyrazinyl.

2. The compound of claim 1 , where L is —CO—.

3. A composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 .

4. The compound of claim 1 , where the compound is selected from one of formulas XXI-XXVI

where X a and X b are independently selected from the group consisting of: hydrogen, halogen, —CN, —NO 2 , —OH, —OR 1 , —C(O)R 1 , —CO 2 R, —O(CO)R 1 , —C(O)NR 1 R 2 , —OC(O)NR 1 R 2 , —SR 1 , —SOR 1 , —SO 2 R 1 , —SO2NR 1 R 2 , —NR 1 R 2 , —NR 1 C(O)R 2 , —NR 1 C(O) 2 R 2 , —NR 1 SO 2 R 2 , —NR 1 (CO)NR 2 R 3 , unsubstituted C 1-8 alkyl, unsubstituted C 2-8 alkenyl, unsubstituted C 2-8 alkynyl, and unsubstituted C 3-8 cycloalkyl;
R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, unsubstituted C 1-6 haloalkyl, unsubstituted C 1-6 alkyl, unsubstituted C 2-5 alkenyl, and unsubstituted C 2-6 alkynyl; or
two of R 1 , R 2 and R 3 together with the atom(s) to which they are attached, may form an unsubstituted 5-, 6- or 7-membered ring; where Y a and Y b are independently selected from the group consisting of: hydrogen, halogen, —CN, —NO 2 , —OH, —OR 4 , —C(O)R 4 , —CO2R 4 , —SR 4 , —SOR 4 , —SO2R 4 , and unsubstituted C 1-4 alkyl;
R 4 is selected from the group consisting of hydrogen, unsubstituted C 1-6 haloalkyl, unsubstituted C 1-6 alkyl, unsubstituted C 3-6 cycloalkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl;
where Z a and Z b are independently selected from the group consisting of: hydrogen, halogen, unsubstituted C 1-8 alkyl, unsubstituted C 2-8 alkenyl, unsubstituted C 2-8 alkynyl, —CN, ═O, —NO 2 , —OR 10 , —OC(O)R 10 , —CO 2 R 10 , —C(O)R 10 , —C(O)NR 11 R 12 , —OC(O)NR 11 R 12 , —NR 10 C(O)R 11 , —NR 10 C(O)NR 11 R 12 , —NR 11 R 12 , —NR 10 CO 2 R 11 , —SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O) 2 NR 11 R 12 , and —NR 10 S(O) 2 R 11 ;
R 10 , R 11 and R 12 are each selected from hydrogen, C 1-8 alkyl, C 2-8 alkenyl, and C 2-8 alkynyl.

5. The compound of claim 4 , where the compound is of formula XXI.

6. The compound of claim 4 , where the compound is of formula XXII.

7. The compound of claim 4 , where the compound is of formula XXIII.

8. The compound of claim 4 , where the compound is of formula XXIV.

9. The compound of claim 4 , where the compound is of formula XXV.

10. The compound of claim 4 , where the compound is of formula XXVI.

11. A compound which is

Assignees

• Chemocentryx Inc

Inventors

• Ungashe Solomon
• Wright John J
• Pennell Andrew
• Wei Zheng
• Melikian Anita

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title