Antibacterial agents: aryl myxopyronin derivatives

1. A compound of formula Ia, Ib or Ic:

or a salt thereof, wherein:

W is sulfur, oxygen, or nitrogen;

X, Y, and Z are individually carbon, sulfur, oxygen, or nitrogen, wherein at least two of X, Y, and Z are carbon;

one of R 1 and R 2 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 1 -C 10 alkoxy, aryloxy, heteroaryloxy, or NR a N b , wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkoxy, tetrahydrofuranyl, or furanyl, and wherein any aryloxy or heteroaryloxy is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkyl, or C 1 -C 5 alkoxy, wherein any C 1 -C 5 alkyl and C 1 -C 5 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy; or

one of R 1 and R 2 is a 5-6-membered saturated, partially unsaturated, or aromatic heterocycle that is optionally substituted by at least one of halogen, hydroxy, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy; and the other of R 1 and R 2 is absent or is one of H, halogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy;

R 3 is absent, or is one of H, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 4 is absent, or is one of H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

V′, W′, X′, Y′, and Z′ are individually carbon or nitrogen; wherein at least three of V′, W′, X′, Y′, and Z′ are carbon;

one of R 1′ and R 2′ is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 1 -C 10 alkoxy, aryloxy, heteroaryloxy, or NR a R b , wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkoxy, tetrahydrofuranyl, or furanyl, and wherein any aryloxy or heteroaryloxy is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkyl, or C 1 -C 5 alkoxy, wherein any C 1 -C 5 alkyl and C 1 -C 5 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy; or

one of R 1′ and R 2′ is a 5-6-membered saturated, partially unsaturated, or aromatic heterocycle that is optionally substituted by at least one of halogen, hydroxy, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy; and the other of R 1′ and R 2′ is absent or is one of H, halogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy;

R 3′ , R 4′ , and R 5′ are each independently absent, H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

W″ is sulfur, oxygen, or nitrogen;

U″, V″, X″, Y″, and Z″ are individually carbon, sulfur, oxygen, or nitrogen, wherein at least three of U″, V″, X″, Y″, and Z″ are carbon;

one of R 1″ and R 2″ is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 1 -C 10 alkoxy, aryloxy, heteroaryloxy, or NR a R b , wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkoxy, tetrahydrofuranyl, or furanyl, and wherein any aryloxy or heteroaryloxy is optionally substituted by at least one of halogen, hydroxy, C 1 -C 5 alkyl, or C 1 -C 5 alkoxy, wherein any C 1 -C 5 alkyl and C 1 -C 5 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy; or

one of R 1″ and R 2″ is a 5-6-membered saturated, partially unsaturated, or aromatic heterocycle that is optionally substituted by at least one of halogen, hydroxy, alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy; and the other of R 1″ and R 2″ is absent or is one of H, halogen, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy, wherein any C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 1 -C 10 alkoxy is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy;

R 3′ is absent or is one of H, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 4″ , R 5″ , and R 6″ are each independently absent, H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 5 and R 6 are individually H or methyl;

G is one of —CH═CH—NHC(O)—R 7 , —CH═CH—NHC(S)—R 7 , —CH 2 CH 2 NHC(O)—R 7 , —CH 2 CH 2 NHC(S)—R 7 , —CH 2 NHNHC(O)—R 7 , or —CH 2 NHNHC(S)—R 7 ;

R 7 is one of C 1 -C 6 alkyl, —O(C 1 -C 6 alkyl), —S(C 1 -C 6 alkyl), or —N(R 8 ) 2 ;

each R 8 is independently one of hydrogen or —C 1 -C 6 alkyl;

R 9 is C 1 -C 10 alkyl or C 2 -C 10 alkenyl, wherein any C 1 -C 10 alkyl or C 2 -C 10 alkenyl is optionally substituted by at least one of halogen, hydroxy, alkoxy, or NR a R b ;

each R a is C 1 -C 10 alkyl that is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy; and

each R b is H or C 1 -C 10 alkyl that is optionally substituted by at least one of halogen, hydroxy, or C 1 -C 5 alkoxy.

2. The compound of formula Ia′, Ib′ or Ic′:

or a salt thereof, wherein:

W is sulfur, oxygen, or nitrogen;

X, Y, and Z are individually carbon, sulfur, oxygen, or nitrogen, wherein at least two of X, Y, and Z are carbon;

one of R 1 and R 2 is C 1 -C 8 alkyl or C 1 -C 8 alkoxy optionally substituted by at least one of halogen, hydroxy, alkoxy, or furanyl; and the other of R 1 and R 2 is absent or is one of H, halogen, or C 1 -C 8 alkyl or C 1 -C 8 alkoxy optionally substituted by at least one of halogen, hydroxy, or alkoxy;

R 3 is absent, or is one of H, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 4 is absent, or is one of H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

V′, W, X′, Y′, and Z′ are individually carbon or nitrogen; wherein at least four of V′, W′, X′, Y′, and Z′ are carbon;

one of R 1′ and R 2′ is C 1 -C 5 alkyl or C 1 -C 8 alkoxy optionally substituted by at least one of halogen, hydroxy, or alkoxy, or furanyl; and the other of R 1′ and R 2′ is absent, or is one of H, halogen, or C 1 -C 8 alkyl or C 1 -C 8 alkoxy optionally substituted by at least one of halogen, hydroxy, or alkoxy;

R 3′ , R 4′ , and R 5′ each is absent, or each of R 3′ , R 4′ , and R 5′ is one of is H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

W″ is sulfur, oxygen, or nitrogen;

U″, V″, X″, Y″, and Z″ are individually carbon, sulfur, oxygen, or nitrogen, wherein at least three of U″, V″, X″, Y″, and Z″ are carbon;

one of R 1″ and R 2″ is C 1 -C 8 alkyl or C 1 -C 5 alkoxy optionally substituted by at least one of halogen, hydroxy, or alkoxy, or furanyl; and the other of R 1 ″ and R 2 ″ is absent, or is one of H, halogen, or C 1 -C 8 alkyl or C 1 -C 8 alkoxy optionally substituted by at least one of halogen, hydroxy, or alkoxy;

R 3″ is absent or is one of H, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl;

R 4″ , R 5″ , and R 6″ each is absent, or each of R 4″ , R 5″ , and R 6″ is H, halogen, C 1 -C 2 alkyl, or halogen-substituted C 1 -C 2 alkyl; and

R 5 and R 6 are individually H or methyl;

G is one of —CH═CH—NHC(O)—R 7 , —CH═CH—NHC(S)—R 7 , —CH 2 CH 2 NHC(O)—R 7 , —CH 2 CH 2 NHC(S)—R 7 , —CH 2 NHNHC(O)—R 7 , or —CH 2 NHNHC(S)—R 7 , R 7 is one of C 1 -C 6 alkyl, —O(C 1 -C 6 alkyl), —S(C 1 -C 6 alkyl), or —N(R 8 ) 2 ; and

each R 8 is independently one of hydrogen or —C 1 -C 6 alkyl.

3. The compound of claim 1 , which is a compound of formula Ia, or a salt thereof.

4. The compound of claim 1 , which is a compound of formula Ib, or a salt thereof.

5. The compound of claim 1 , which is a compound of formula Ic, or a salt thereof.

6. The compound of claim 1 , or a salt thereof, wherein R 6 is H.

7. The compound of claim 1 , or a salt thereof, wherein R 6 is methyl.

8. A compound selected from

and salts thereof.

9. The compound of claim 1 , or a salt thereof, wherein the salt is a pharmaceutically acceptable salt.

10. A composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.