Sulphonamides as methionine metabolic pathway inhibitors

Abstract

The present invention provides novel sulphonamide inhibitors of cystathionin gamma synthase (CGS), their use as selective and non-selective herbicides, agricultural and non-agricultural herbicides, herbicides in integrated pest management, herbicides for gardening, clearing waste ground, clearing industrial or constructions sites, clearing railways and railway embankments, pesticide, fungicide, agricultural plant stimulant or antimicrobial agent. Also provided is a method for the control of undesired vegetation or clearing areas from the undesired vegetation comprising applying to the locus of said undesired vegetation, to the undesired plants or to a habitat thereof, a herbicidally effective amount of the compound of the present invention.

1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         where T is a phenyl radical of Formula (A1) or (A2), a benzyl radical of Formula (B), a benzyl or phenyl-vinyl radical of Formula (C), a naphthyl radical of Formula (D1), a tetralinyl radical of formula (D2), an indanyl radical of formula (D3), or a 1-phenyl-1H-pyrazolyl radical of formula (E): 
       
       
         
           
           
               
               
           
         
         where   is a single or double bond, and the aromatic ring of radicals (A2), (B), (C), (D2) and (D3), or the aromatic ring (1) of radical (D1) is optionally substituted with one to three substituents R attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano or nitro group; 
         R 3  is a five-membered heteroaromatic ring having one to three heteroatoms selected from N, O and S, and optionally substituted with (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy or hydroxy group, or halogen atom; 
         R 4  is hydrogen, or (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl or (C 1 -C 3 )-alkoxy group; and 
       
       (i) provided that when T is the phenyl radical of the Formula (A1), then
 R 1  is hydrogen, and 
 R 2  is a phenyl group optionally substituted with one to three same or different substituents independently selected from a halogen atom, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, amino, cyano, hydroxy, nitro, carboxylic acid, (C 1 -C 3 )-alkylcarboxylic acid, carboxylate, carboxamide, (C 1 -C 3 )-alkylcarboxylate and (C 1 -C 3 )-alkylcarboxamide group; 
 
       (ii) provided that when T is the phenyl radical of the Formula (A2), then
 R 1  is hydrogen, and 
 R 2  is a phenyl group substituted with a five-membered heteroaromatic ring of the formula: 
 
       
         
           
           
               
               
           
         
         where X and Y are independently CH or N; 
         Z is C—R 9  or N; 
         R 9  is hydrogen, halogen, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, hydroxy, (C 1 -C 3 )-alkoxy, carboxylate, (C 1 -C 3 )-alkylcarboxylate, carboxylic acid, (C 1 -C 3 )-alkylcarboxylic acid, carboxamide, (C 1 -C 3 )-alkylcarboxamide, cyano, nitro, phenyl, benzyl or phenylamino, wherein said phenyl, benzyl or phenylamino are optionally substituted with one to three same or different substituents independently selected from halogen, (C 1 -C 3 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 3 )-haloalkyl, hydroxy, (C 1 -C 3 )-alkoxy, cyano, amino, carboxylic acid and nitro group; 
         L is N—R 10 , O or S; and 
         R 10  is hydrogen, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, benzyl or phenyl, wherein said benzyl or phenyl are optionally substituted with one to three same or different substituents independently selected from halogen, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, hydroxy, (C 1 -C 3 )-alkoxy, cyano, amino and nitro group; 
       
       (iii) provided that when T is the benzyl radical of the formula (B), then
 R 1  is hydrogen, and 
 R 2  is selected from the following heteroaromatic fused bicyclic radicals having two to three nitrogen atoms: 
 
       
         
           
           
               
               
           
         
         where R 5  is hydrogen or (C 1 -C 3 )-alkyl group; 
       
       (iv) provided that when T is the benzyl or phenyl-vinyl radical of Formula (C), then
 R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, a fused bicyclic radical selected from: 
 
       
         
           
           
               
               
           
         
         where R 6  is attached to any available heterocyclic ring carbon atom, and selected from hydrogen, carboxylate, carboxylic acid, carboxamide, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkylcarboxylate, (C 1 -C 3 )-alkylcarboxylic acid or (C 1 -C 3 )-alkylcarboxamide group; 
       
       (v) provided that when T is the naphthyl radical of Formula (D1), a tetralinyl radical of formula (D2) or an indanyl radical of formula (D3), then
 R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, a pyrrolidinyl radical or a fused bicyclic radical selected from: 
 
       
         
           
           
               
               
           
         
         where the pyrrolidinyl heterocyclic ring of said radicals is optionally substituted with one or two substituents R 7  attached to any available pyrrolidinyl ring carbon atom and independently selected from carboxylate, (C 1 -C 3 )-alkylcarboxylate, carboxylic acid, (C 1 -C 3 )-alkylcarboxylic acid, (C 1 -C 3 )-alkylcarboxamide or carboxamide group; and 
         where the phenyl aromatic or pyridinyl heteroaromatic ring of said radicals is optionally substituted with one to three substituents R 8  attached to any available phenyl or pyridinyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano or nitro group; and 
       
       (vi) provided that when T is the 1-phenyl-1H-pyrazolyl radical of formula (E), then
 R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, an indolinyl radical of the formula: 
 
       
         
           
           
               
               
           
         
         where the pyrrolidinyl ring of said radical is substituted with one R 7  group attached to any available pyrrolidinyl ring carbon atom, and selected from methyl, carboxamide, carboxylate, carboxylic acid or acetic acid group; and 
         where the phenyl aromatic ring of said radical is optionally substituted with one to three substituents R 8  attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy group or halogen atom. 
       
     
     
         2 . The compound of  claim 1  having Formula (IA1): 
       
         
           
           
               
               
           
         
         wherein R 2  is a phenyl group optionally substituted with one to three same or different substituents independently selected from a halogen atom, (C 1 -C 3 )-alkyl, carboxylic acid, carboxylate, carboxamide, (C 1 -C 3 )-alkylcarboxylic acid and (C 1 -C 3 )-alkylcarboxylate; and 
         R 3  is a five-membered heteroaromatic ring 1,3-thiazolyl of the formula: 
       
       
         
           
           
               
               
           
         
         where said five-membered heteroaromatic ring is optionally substituted with a halogen atom, or hydroxy, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl or (C 1 -C 3 )-alkoxy group. 
       
     
     
         3 . The compound of  claim 2  selected from: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1  having Formula (IA2): 
       
         
           
           
               
               
           
         
         where R is hydrogen or halogen atom, or methoxy or trifluoromethyl group; 
         X and Y are independently CH or N; 
         Z is C—R 9  or N; 
         R 9  is hydrogen, ethyl, cyclopentyl, trifluoromethyl, hydroxy, benzyl or phenylamino, wherein said benzyl or phenylamino are optionally substituted with one to three same or different substituents independently selected from halogen, methyl, trufluoromethyl, hydroxy, methoxy or carboxylic acid group; 
         R 10  is hydrogen, methyl or benzyl group. 
       
     
     
         5 . The compound of  claim 4  selected from: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1  having Formula (TB): 
       
         
           
           
               
               
           
         
         where the phenyl ring of said compound is optionally substituted with one to three substituents R attached to any available phenyl ring carbon atom and independently selected from hydrogen, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano or nitro group; and 
         R 2  is selected from the following heteroaromatic fused bicyclic radicals having two or three nitrogen atoms: 
       
       
         
           
           
               
               
           
         
         wherein R 5  is hydrogen or (C 1 -C 3 )-alkyl group. 
       
     
     
         7 . The compound of  claim 6  selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1  selected from: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 1  having Formula (IC): 
       
         
           
           
               
               
           
         
            where is a double bond; 
         the phenyl ring of said compound is optionally substituted with one to three substituents R attached to any available phenyl ring carbon atom and independently selected from hydrogen, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano and nitro group, and 
         R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, a pyrrolidinyl radical or a fused bicyclic radical selected from: 
       
       
         
           
           
               
               
           
         
         where the pyrrolidinyl or piperidinyl heterocyclic ring of said radicals is optionally substituted with one or two substituents R 7  attached to any available pyrrolidinyl or piperidinyl ring carbon atom and independently selected from halogen, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, carboxylate, (C 1 -C 3 )-alkylcarboxylate, carboxylic acid, cyano, (C 1 -C 3 )-alkylcarboxylic acid, (C 1 -C 3 )-alkylcarboxamide or carboxamide group; and 
         the phenyl aromatic or pyridinyl heteroaromatic ring of said radicals is optionally substituted with one to three substituents R 8  attached to any available phenyl or pyridinyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, halogen, amino, cyano or nitro group. 
       
     
     
         10 . The compound of  claim 9  selected from: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 1  having Formula (ID1): 
       
         
           
           
               
               
           
         
         where the aromatic ring (1) of the compound is optionally substituted with one to three substituents R attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano or nitro group; and 
         R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, an indolinyl radical of the formula: 
       
       
         
           
           
               
               
           
         
         where the pyrrolidinyl ring of said radical is optionally substituted with one or two substituents R 7  attached to any available pyrrolidinyl ring carbon atom and independently selected from carboxylic acid, carboxylate, (C 1 -C 3 )-alkylcarboxylic acid or (C 1 -C 3 )-alkylcarboxylate group; and 
         where the phenyl aromatic ring of said radical is optionally substituted with one to three substituents R 8  attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy or halogen. 
       
     
     
         12 . The compound of  claim 11 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 1  having Formula (ID2): 
       
         
           
           
               
               
           
         
         where the phenyl ring of the compound is optionally substituted with one to three substituents R attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano or nitro group; and 
         R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, an indolinyl radical of the formula: 
       
       
         
           
           
               
               
           
         
         where the pyrrolidinyl ring of said radical is optionally substituted with one or two substituents R 7  attached to any available pyrrolidinyl ring carbon atom and independently selected from carboxylic acid, carboxylate, (C 1 -C 3 )-alkylcarboxylic acid or (C 1 -C 3 )-alkylcarboxylate group; and 
         where the phenyl aromatic ring of said radical is optionally substituted with one to three substituents R 8  attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy or halogen. 
       
     
     
         14 . The compound of  claim 1  having Formula (ID3): 
       
         
           
           
               
               
           
         
         where the phenyl ring of the compound is optionally substituted with one to three substituents R attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkoxy, hydroxy, halogen, amino, cyano or nitro group; and 
         R 1  and R 2  taken together form around the nitrogen atom, to which they are attached, an indolinyl radical of the formula: 
       
       
         
           
           
               
               
           
         
         where the pyrrolidinyl ring of said radical is optionally substituted with one or two substituents R 7  attached to any available pyrrolidinyl ring carbon atom and independently selected from carboxylic acid, carboxylate, (C 1 -C 3 )-alkylcarboxylic acid or (C 1 -C 3 )-alkylcarboxylate group; and 
         where the phenyl aromatic ring of said radical is optionally substituted with one to three substituents R 8  attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy or halogen. 
       
     
     
         15 . The compound of  claim 14 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 1  having Formula (IE): 
       
         
           
           
               
               
           
         
         where the pyrrolidinyl ring of said compound is substituted with one R 7  group attached to any available pyrrolidinyl ring carbon atom, and selected from methyl, carboxamide, carboxylate, carboxylic acid or acetic acid group; and 
         where the phenyl aromatic ring of said radical is optionally substituted with one to three substituents R 8  attached to any available phenyl ring carbon atom and independently selected from (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy group or halogen atom. 
       
     
     
         17 . The compound of  claim 16 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 1  for use as a selective herbicide, non-selective herbicide, agricultural herbicide, non-agricultural herbicide, herbicide in integrated pest management, herbicide in gardening, herbicide in clearing waste ground, herbicide in clearing industrial or constructions sites, herbicide in clearing railways and railway embankments, pesticide, fungicide, agricultural plant stimulant or antimicrobial agent. 
     
     
         19 . A method for the control of undesired vegetation or clearing areas from the undesired vegetation comprising applying to the locus of said undesired vegetation, to the undesired plants or to a habitat thereof, a herbicidally effective amount of the compound of  claim 1 . 
     
     
         20 . The method of  claim 19 , wherein said locus is agricultural areas, crop fields, gardens, waste grounds, industrial or constructions sites, railways or railway embankments.