2-(aryl or heteroaryl-)phenyl (AZA)benzofuran compounds for the treatment of hepatitis C

Patent metadata

Field	Value
Publication number	US-9840511-B2
Application number	US-201515312022-A
Country	US
Kind code	B2
Filing date	May 19, 2015
Priority date	May 21, 2014
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

Compounds of Formula I, including their salts, as well as compositions and methods of using the compounds are set forth. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV: formula (I).

First claim

We claim:

1. A compound of Formula I, including pharmaceutically acceptable salts thereof:

wherein
m is 0 or 1;
X is N or C—R 10 ;
R 1 is methyl;
R 2 is Ar 1 ;
Ar 1 is phenyl, 5-membered heteroaryl or 6-membered heteroaryl, and is substituted with 0-3 substituents selected from the group of cyano, halo, alkyl, cycloalkyl, haloalkyl, OH, OR 101 , haloalkoxy, NH 2 , NR 102 R 103 , COOR 101 , CONR 102 R 103 , S(O) 2 R 101 , S(O) 2 NR 102 R 103 , and NR 101 CONR 102 R 103 ;
R 101 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R 102 , R 103 are each independently hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy; or
R 102 and R 103 can form a ring by joining two atoms, one from each of R 102 and R 103 ;
R 3 is hydrogen, halo, or alkyl;
R 4 , R 5 , R 6 , R 7 , R 8 are each independently selected from the group of hydrogen, halo, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, hydroxyalkyl, hydroxycycloalkyl, alkoxyalkyl, alkoxycycloalkyl, alkoxy, hydroxyalkyloxy, alkoxyalkyloxy, COOR 201 and CON(R 202 )(R 203 );
R 201 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R 202 , R 203 are each independently selected from the group of hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkyl alkynyl, cyclic ether, cyclic amine, lactame, fused bicyclic alkyl, bridged bicyclic alkyl, spiro bicyclic alkyl, fused bicyclic ether, bridged bicyclic ether, spiro bicyclic ether, fused bicyclic amine, bridged bicyclic amine, and spiro bicyclic amine, with 0-3 substituents selected from the group of halo, OH, OR 104 , NH 2 , NR 105 R 106 , COOR 104 , CONR 105 R 106 , S(O) 2 R 104 , S(O) 2 NR 105 R 106 , NR 104 CONR 105 R 106 , OR 104 CONR 105 R 106 , C(═NR 107 )NR 105 R 106 , NR 108 C(═NR 107 )NR 105 R 106 , haloalkoxy, Ar 2 , O—Ar 2 , and NR 105 —Ar 2 ; or
R 202 and R 203 can form a ring by joining two atoms, one from each of R 202 and R 203 ;
R 202 and R 203 can also form bicyclic or tricyclic rings by joining multiple atoms from each of R 202 and R 203 ;
R 104 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R 105 , R 106 are each independently hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy; or
R 105 and R 106 can form a ring by joining two atoms, one from each of R 105 and R 106 ;
R 107 , R 108 are each independently hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy; or
R 107 and R 108 can form a ring by joining two atoms, one from each of R 107 and R 108 ;
Ar 2 is phenyl, 5-membered heteroaryl or 6-membered heteroaryl, and is substituted with 0-3 substituents selected from the group of cyano, halo, alkyl, cycloalkyl, haloalkyl, OH, OR 204 , haloalkoxy, NH 2 , NR 205 R 206 , COOR 204 , CONR 205 R 206 , S(O) 2 R 204 , S(O) 2 NR 205 R 206 , and NR 204 CONR 205 R 206 ;
R 204 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R 205 , R 206 are each independently hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy; or
R 205 and R 206 can form a ring by joining two atoms, one from each of R 205 and R 206 ;
R 9 is selected from the group of hydrogen, halo, alkyl, cycloalkyl, alkoxy, Ar 3 and NR 301 R 302 ;
R 301 is selected from the group of hydrogen, alkyl, cycloalkyl, (cycloalkyl)alkyl, benzyl, alkylcarbonyl, haloalkyl carbonyl, phenyl carbonyl, (alkoxyphenyl)carbonyl, alkylsulfonyl, phenylsulfonyl, (alkoxyphenyl)sulfonyl, and (haloalkoxyphenyl)sulfonyl;
R 302 is hydrogen, alkyl, hydroxyalkyl, or alkoxyalkyl; or
R 301 and R 302 taken together with the nitrogen to which they are attached is oxazolidinonyl or dioxothiazinyl;
Ar 3 is phenyl, 5-membered heteroaryl or 6-membered heteroaryl, and is substituted with 0-3 substituents selected from the group of cyano, halo, alkyl, cycloalkyl, haloalkyl, OH, OR 303 , haloalkoxy, NH 2 , NR 304 R 305 , COOR 303 , CONR 304 R 305 , S(O) 2 R 303 , S(O) 2 NR 304 R 305 , and NR 303 CONR 304 R 305 ;
R 303 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R 304 , R 305 are each independently hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy; or
R 304 and R 305 can form a ring by joining two atoms, one from each of R 304 and R 305 ;
R 10 is hydrogen, alkyl, halo, N(R 401 )(R 402 ), or alkylsulfonyl;
R 401 and R 402 are each independently selected from the group of hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, alkylsulfonyl, or alkylsulfonylalkyl;
or N(R 401 )(R 402 ) taken together is azetidinyl, pyrrolidinyl, piperidinyl, or piperazinyl, and is substituted with 0-2 substituents selected from alkyl, hydroxyalkyl, and hydroxy.

2. A compound of claim 1 wherein m=0.

3. A compound of claim 2 wherein R 1 is alkyl.

4. A compound of claim 3 wherein R 5 is CON(R 202 )(R 203 ).

5. A compound of claim 1 wherein R 202 and R 203 are hydrogen or alkyl.

6. A compound of claim 1 wherein R 2 is a 5-membered heteroaryl group.

7. A compound of claim 6 wherein R 2 has 2 to 3 nitrogens.

8. A compound of claim 1 wherein R 9 is selected from the group of haloalkyl, NR 301 , R 302 and Ar 3 .

9. A compound of claim 8 wherein haloalkyl is 1-3 fluoroalkyl.

10. A compound of claim 9 wherein said alkyl is propyl.

11. A compound of claim 1 wherein R 10 is hydrogen.

12. A compound, including pharmaceutically acceptable salts thereof, which is selected from the group of:

13. A compound, including pharmaceutically acceptable salts thereof, which is selected from the group of:

14. A composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient, and/or diluent.

15. A composition comprising a compound of claim 12 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient, and/or diluent.

16. A composition comprising a compound of claim 13 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient, and/or diluent.

17. A compound as claimed in claim 8 , wherein R 9 is NR 301 , and R 301 is selected from alkyl and alkylsulfonyl.

Assignees

• Bristol Myers Squibb Co
• Bristol-Meyers Squibb Company

Inventors

• Wang Tao
• Zhang Zhongxing
• Kadow John F

Classifications

• C07D491/048 Primary

  the oxygen-containing ring being five-membered · CPC title

• C07D307/84

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title

• C07D405/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61P31/18

  for HIV · CPC title