Acetyl-CoA carboxylase modulators

Patent metadata

Field	Value
Publication number	US-10995070-B2
Application number	US-201916239946-A
Country	US
Kind code	B2
Filing date	Jan 4, 2019
Priority date	Jun 13, 2013
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

Provided herein are compounds that exhibit activity as acetyl-CoA carboxylase modulators (e.g., inhibitors) and are useful, for example, in methods for the control of fungal pathogens in plants.

First claim

What is claimed is:

1. A method of controlling fungal pathogens, the method comprising administering to a plant, a seed or soil a composition comprising an effective amount of a compound of Formula II, or a salt thereof,

wherein
R 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;
R 2 is selected from the group consisting of aryl and heteroaryl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, OH, CN, alkyl, alkoxy, haloalkyl, haloalkoxy, alkenyl, C 1 to C 4 hydroxyalkyl, N(R 7 R 8 ), and NR 9 C(O)R 10 , wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen and alkyl, and wherein R 9 is selected from the group consisting of hydrogen and alkyl and R 10 is alkyl;
R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, halogen, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, C 1 to C 4 hydroxyalkyl, N(R 7 R 8 ), NR 9 C(O)R 10 , and C(O)R 11 , wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen and alkyl, and wherein R 9 is selected from the group consisting of hydrogen and alkyl and R 10 and R 11 are alkyl;
X is selected from the group consisting of a bond, CH 2 , O, S, NH, and N(CH 3 );
Y is selected from the group consisting of hydrogen, a prodrug of a carboxylic acid and a carboxylic acid isostere, wherein the prodrug of a carboxylic acid is selected from the group consisting of CH 2 OH and C(O)OR 11 , wherein R 11 is selected from the group consisting of methyl, ethyl, 2-oxopropyl, 2- morpholinoethyl, and pivaloyloxymethyl, and wherein the carboxylic acid isostere is selected from the group consisting of tetrazolyl, aminosulfonyl, acylaminosulfonyl, methylsulfonylcarbamyl, thiazolidinedionyl, oxazolidinedionyl, oxadiazolonyl, P(O)(OH) 2, P(O)(OH)H, and SO 3 H; and
Z is selected from the group consisting of aryl and heteroaryl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, C 1 to C 4 hydroxyalkyl, CN, and C(H)O,
with the proviso that when R 2 is phenyl, Z is phenyl, and Y is C(O)OCH 2 CH 3, R 4 is other than halogen.

2. The method of claim 1 wherein the compound is of Formula IIa or a salt thereof,

wherein
R 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;
R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, halogen, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, C 1 to C 4 hydroxyalkyl, N(R 7 R 8 ), NR 9 C(O)R 10 , and C(O)R 11 , wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen and alkyl, and wherein R 9 is selected from the group consisting of hydrogen and alkyl and R 10 and R 11 are alkyl;
X is selected from the group consisting of CH 2 , O, S, NH, and N(CH 3 ); and
Y is selected from the group consisting of hydrogen and a carboxylic acid isostere, wherein the carboxylic acid isostere is selected from the group consisting of tetrazolyl, aminosulfonyl, acylaminosulfonyl, methylsulfonylcarbamyl, thiazolidinedionyl, oxazolidinedionyl, oxadiazolonyl, P(O)(OH) 2 , P(O)(OH)H, and SO 3 H.

3. The method of claim 1 wherein the compound is of Formula IIb or a salt thereof,

wherein
R 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;
R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, halogen, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, C 1 to C 4 hydroxyalkyl, N(R 7 R 8 ), NR 9 C(O)R 10 , and C(O)R 11 , wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen and alkyl, and wherein R 9 is selected from the group consisting of hydrogen and alkyl and R 10 and R 11 are alkyl;
Y is a carboxylic acid isostere selected from the group consisting of tetrazolyl, aminosulfonyl, acylaminosulfonyl, methylsulfonylcarbamyl, thiazolidinedionyl, oxazolidinedionyl, oxadiazolonyl, P(O)(OH) 2 , P(O)(OH)H, and SO 3 H; and
E is selected from the group consisting of S, O, and N(CH 3 ).

4. The method of claim 1 wherein the compound is of Formula IIc or a salt thereof,

wherein
R 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;
R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, halogen, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, C 1 to C 4 hydroxyalkyl, N(R 7 R 8 ), NR 9 C(O)R 10 , and C(O)R 11 , wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen and alkyl, and wherein R 9 is selected from the group consisting of hydrogen and alkyl and R 10 and R 11 are alkyl;
X is selected from the group consisting of CH 2 , O, S, NH, and N(CH 3 ); and
Y is selected from the group consisting of hydrogen and a prodrug of carboxylic acid, wherein the prodrug of a carboxylic acid is selected from the group consisting of CH 2 OH and C(O)OR 11 , wherein R 11 is selected from the group consisting of methyl, ethyl, 2-oxopropyl, 2-morpholinoethyl, and pivaloyloxymethyl; with the proviso that when Y is C(O)OCH 2 CH 3, R 4 is other than halogen.

5. The method of claim 1 wherein the compound is of Formula IId or a salt thereof,

wherein
R 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;
R 3 , R 4 , R 5 , and R 6 are each independently selected from the group consisting of hydrogen, halogen, OH, alkyl, alkoxy, haloalkyl, haloalkoxy, C 1 to C 4 hydroxyalkyl, N(R 7 R 8 ), NR 9 C(O)R 10 , and C(O)R 11 , wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen and alkyl, and wherein R 9 is selected from the group consisting of hydrogen and alkyl and R 10 and R 11 are alkyl;
Y is a prodrug of carboxylic acid, wherein the prodrug of a carboxylic acid is selected from the group consisting of CH 2 OH and C(O)OR 11 , wherein R 11 is selected from the group consisting of methyl, ethyl, 2-oxopropyl, 2-morpholinoethyl, and pivaloyloxymethyl; and
E is selected from the group consisting of S, O, and N(CH 3 ).

6. The method of claim 1 wherein R 2 is phenyl.

7. The method of claim 1 wherein Z is selected from the group consisting of phenyl and thienyl.

8. The method of claim 1 wherein R 1 is hydrogen.

9. The method of claim 1 wherein the method comprises administering the composition to a seed.

10. A treated seed prepared according to the method of claim 9 .

11. The method of claim 1 wherein the method comprises exogenously administering the composition to a plant.

12. The method of claim 1 wherein the compound is of Formula IIb or a salt thereof,

wherein
R 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, and ha

Assignees

• Monsanto Technology Llc

Inventors

• Slomczynska Urszula
• Dimmic Matthew W
• Haakenson Jr William P
• Bennett Jennifer L
• Shortt Barry J
• Taylor Christina M
• Williams Deryck Jeremy

Classifications

• A01N41/10

  Sulfones; Sulfoxides · CPC title

• A01N43/18

  with sulfur as the ring hetero atom · CPC title

• A01N43/16

  with oxygen as the ring hetero atom · CPC title

• A61K31/395

  having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins · CPC title

• A01N37/22

  the nitrogen atom being directly attached to an aromatic ring system, e.g. anilides · CPC title