Acetyl-CoA carboxylase modulators

Patent metadata

Field	Value
Publication number	US-9844218-B2
Application number	US-201414896605-A
Country	US
Kind code	B2
Filing date	Jun 13, 2014
Priority date	Jun 13, 2013
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

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 I, Formula II, or a salt thereof,

wherein
R 2 is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, CH 3 , OCH 3 , CF 3 , OCF 3 , and CN;
R 3 is selected from the group consisting of hydrogen, CN, ethynyl, CH 2 N(R 9 R 10 ), and C(O)N(R 9 R 10 ), wherein R 9 and R 10 are each independently selected from the group consisting of hydrogen and alkyl;
R 4 is selected from the group consisting of haloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, alkenyl, hydroxyalkyl, hydroxyl, N(R 9 R 10 ), NR 11 C(O)R 12 , and O(CO)R 13 , wherein R 9 and R 10 are independently selected from the group consisting of hydrogen and alkyl, R 11 is selected from the group consisting of hydrogen and alkyl, R 12 is alkyl, and R 13 is alkyl;
R 5 is selected from the group consisting of hydrogen and alkyl; or R 4 and R 5 together form a fused cycloalkyl or heterocycloalkyl ring having from 5 to 6 ring atoms selected from the group consisting of carbon, nitrogen, and oxygen;
R 6 is selected from the group consisting of alkyl, haloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy; or
R 5 and R 6 together form a fused cycloalkyl or heterocycloalkyl ring having from 5 to 6 ring atoms selected from the group consisting of carbon, nitrogen, and oxygen; and
E is selected from the group consisting of S, O, N(H), N(CH 3 ), and CH 2 ;
and wherein in Formula I, R 1 is selected from the group consisting of OH and N(R 7 R 8 ), wherein R 7 and R 8 are independently selected from the group consisting of hydrogen, OH, and CH 3 ;
and in Formula II, R 1 is selected from the group consisting of a prodrug of a carboxylic acid and a carboxylic acid isostere.

2. The method of claim 1 wherein R 2 is selected from the group consisting of pyridyl, pyrimidyl, and thienyl.

3. The method of claim 1 , wherein the method comprises administering to a plant, a seed or soil a composition comprising an effective amount of a compound of Formula I or a salt thereof,

wherein
R 1 is selected from the group consisting of OH and N(R 7 R 8 ), wherein R 7 and R 8 are independently selected from the group consisting of hydrogen, OH, and CH 3 ;
R 2 is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, CH 3 , OCH 3 , CF 3 , OCF 3 , and CN;
R 3 is selected from the group consisting of hydrogen, CN, ethynyl, CH 2 N(R 9 R 10 ), and C(O)N(R 9 R 10 ), wherein R 9 and R 10 are each independently selected from the group consisting of hydrogen and alkyl;
R 4 is selected from the group consisting of haloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, alkenyl, hydroxyalkyl, hydroxyl, N(R 9 R 10 ), NR 11 C(O)R 12 , and O(CO)R 13 , wherein R 9 and R 10 are independently selected from the group consisting of hydrogen and alkyl, R 11 is selected from the group consisting of hydrogen and alkyl, R 12 is alkyl, and R 13 is alkyl;
R 5 is selected from the group consisting of hydrogen and alkyl; or R 4 and R 5 together form a fused cycloalkyl or heterocycloalkyl ring having from 5 to 6 ring atoms selected from the group consisting of carbon, nitrogen, and oxygen;
R 6 is selected from the group consisting of alkyl, haloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy; or
R 5 and R 6 together form a fused cycloalkyl or heterocycloalkyl ring having from 5 to 6 ring atoms selected from the group consisting of carbon, nitrogen, and oxygen; and
E is selected from the group consisting of S, O, N(H), N(CH 3 ), and CH 2 .

4. The method of claim 3 wherein R 1 is OH.

5. The method of claim 3 wherein R 2 is selected from the group consisting of aryl and heteroaryl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, CH 3 , OCH 3 , CF 3 , OCF 3 , and CN.

6. The method of claim 5 wherein R 2 is phenyl.

7. The method of claim 3 wherein R 3 is CN.

8. The method of claim 3 wherein R 4 is selected from the group consisting of CF 3 , thienyl, and optionally substituted phenyl.

9. The method of claim 8 wherein R 4 is selected from the group consisting of 4-halophenyl and 4-alkoxyphenyl.

10. The method of claim 3 wherein R 5 is hydrogen.

11. The method of claim 3 wherein R 6 is selected from the group consisting of methyl, ethyl, thienyl, furanyl, and optionally substituted phenyl.

12. The method of claim 3 wherein E is selected from the group consisting of S, O, and CH 2 .

13. The method of claim 12 wherein E is S.

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

15. A treated seed prepared according to the method of claim 14 .

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

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

wherein
R 2 is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, CH 3 , OCH 3 , CF 3 , OCF 3 , and CN;
R 3 is selected from the group consisting of hydrogen, CN, ethynyl, CH 2 N(R 9 R 10 ), and C(O)N(R 9 R 10 ), wherein R 9 and R 10 are each independently selected from the group consisting of hydrogen and alkyl;
R 4 is selected from the group consisting of haloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, each of which may be optionally independently substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, alkenyl, hydroxyalkyl, hydroxyl, N(R 9 R 10 ), NR 11 C(O)R 12 , and O(CO)R 13 , wherein R 9 and R 10 are independently selected from the group consisting of hydrogen and alkyl, R 11 is selected from the group consisting of hydrogen and alkyl, R 12 is alkyl, and R 13 is alkyl;
R 5 is selected from the group consisting of hydrogen and alkyl; or R 4 and R 5 together form a fused cycloalkyl or heterocycloalkyl ring having from 5 to 6 ring atoms selected

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
• Slater Martin

Classifications

• C07D213/85

  in position 3 · CPC title

• A01N37/10

  Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof · CPC title

• C07D215/54

  attached in position 3 · CPC title

• C07D409/14

  containing three or more hetero rings · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title