2-Pyridyl-1,2-benzisothiazolinone-1,1-dioxides and their use as selective protease inhibitors

• US 4,369,183 A
• Filed: 02/02/1981
• Issued: 01/18/1983
• Est. Priority Date: 09/06/1979
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Jones, Howard, Zimmerman, Morris, Clark, Robert L.
• Primary Examiner(s): Jiles, Henry R.
• Assistant Examiner(s): HARKAWAY, NATALIA
• Application Number:
  US06/230,205
• Time in Patent Office: 715 Days
• Field of Search: 546/270, 424/263, 424/266
• US Class Current: 514/338
• CPC Class Codes: C07D 275/04 condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 275/06 with hetero atoms directly attached to the ring sulfur atom

Abstract

The invention concerns novel 2-aryl-1,2-benzisothiazolinone-1,1-dioxide compounds; methods for their preparation; pharmaceutical compositions containing them as an active ingredient; and methods of selectively inhibiting proteases, especially elastase, and of treating emphysema, rheumatoid arthritis, and various inflammatory diseases, for example, bronchial inflammation.

Claims

1. A compound of the formula:

##STR24## wherein R is ##STR25## where m is 1 to 2; and

Y is independently selected from (1) fluoro;

(2) nitro, except that where Y is only nitro, m must be 1 or 2 and Y must be 2,4- or 3,5-dinitro;

(3) trifluoromethyl;

(4) cyano;

(5) C_1-3 alkoxycarbonyl;

(6) C_1-3 alkylcarbonyl;

(7) carboxyl;

(8) carbamoyl;

(9) C_1-3 alkylacylamino;

(10) C_1-3 alkylsulfonyl;

(11) N,N-di(C_1-3 alkyl) sulfamyl;

(12) trifluoromethoxy;

(13) trifluoromethylthio;

(14) trifluoromethylsulfonyl; and

(15) trifluoromethylsulfinyl;

2. A compound of claim 1 wherein m is 1 or 2 and Y is nitro or cyano.

3. The compound of claim 1 which is 2-(3-nitropyrid-2-yl)-1,2-benzisothiazolinone-1,1-dioxide.

4. The compound of claim 1 which is 2-(5-cyanopyrid-2-yl)-1,2-benzisothiazolinone-1,1-dioxide.

5. The compound of claim 1 which is 2-(3,5-dinitropyrid-2-yl)-1,2-benzisothiazolinone-1,1-dioxide.

6. A method of selectively inhibiting proteases, comprising the administration to a patient a therapeutically effective amount of the compound of claim 1.

7. The method of claim 6 wherein m is 1 or 2 and Y is nitro or cyano.

8. A pharmaceutical composition for selectively inhibiting proteases comprising a non-toxic pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the formula:

##STR26## wherein R is ##STR27## where m is 1 to 2; and

Y is independently selected from (1) fluoro;

(2) nitro, except that where Y is only nitro, m must be 1 or 2 and Y must be 2,4- or 3,5-dinitro;

(3) trifluoromethyl;

(4) cyano;

(5) C_1-3 alkoxycarbonyl;

(6) C_1-3 alkylcarbonyl;

(7) carboxyl;

(8) carbamoyl;

(9) C_1-3 alkylacylamino;

(10) C_1-3 alkylsulfonyl;

(11) N,N-di(C_1-3 alkyl) sulfamyl;

(12) trifluoromethoxy;

(13) trifluoromethylthio;

(14) trifluoromethylsulfonyl; and

(15) trifluoromethylsulfinyl.

9. The composition of claim 8 wherein m is 1 or 2 and Y is nitro or cyano.