Compounds as cannabinoid receptor ligands

1. A method for treating inflammatory disorders in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound having formula (I)

or pharmaceutically acceptable salts thereof, wherein

L is C═O, C═S, S(O) 2 , or C═NCN;

R 1 is alkyl, alkenyl, alkynyl —(CR a R b ) m —OH, —(CR a R b ) m —O(alkyl), —(CR a R b ) m —CN, haloalkyl, or G 1 ;

R 2 is alkyl, alkenyl, alkynyl, G 1 , —C(R Zb )═NO(R Z1 ), —O(R Za ), —N(R Z1 )(R Z2b ), —(CR a R b ) m —N 3 , —(CR a R b ) m —CN, haloalkyl, —(CR a R b ) m —O(R Za ), —(CR a R b ) m —S(R Zb ), —(CR a R b ) m —C(O)O (R Zb ), —(CR a R b ) m —C(O)N(R Z1 )(R Z2a ), —(CR a R b ) m —SO 2 N(R Z1 )(R Z2a ), —(CR a R b ) m —C(O)(R Zb ), —(CR a R b ) m —SO 2 (R Zd ), —SO 2 (R Zd ), —(CR a R b ) m —C(R Zb )═NO(R Z1 ), —(CR a R b ) m —N(R Z1 )(R Z2b ), or —(CR a R b ) m -G 1 ;

R 3 is hydrogen, alkyl, halogen, —CN, -G 2 , haloalkyl, or —(CR a R b ) m -G 2 ;

R 4 is alkyl, alkenyl, alkynyl, —(CR a R b ) n —CN, —(CR a R b ) n —OH, —(CR a R b ) n —O(alkyl), haloalkyl, G 2 , or —(CR a R b ) m -G 2 ; or

R 2 and R 3 or R 3 and R 4 , together with the atoms to which they are attached, form a five-, six-, or seven-membered monocyclic ring containing zero or one additional double bond, zero or one additional heteroatom selected from the group consisting of O, S, N, and N(H), each said ring is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents (R 21 ) selected from the group consisting of oxo, alkyl, alkenyl, alkyrtyl, halogen, —CN, —O(R 1a ), —C(O)OH, —C(O)O(alkyl), —C(O)(R 1a ), —N (R Z3 )(R 3a ), —N(R 3a )C(O)R 1a , —N(R 3a )C(O)O(R 1a ), —N(R 3a )C(O)N(R Z3 )(R 3a ), —N(R 3a )S(O) 2 (R 2a ), —N(R 3a )S(O) 2 N(R Z3 )(R 3a ), —SO 2 (R 2a ), —C(O)N(R Z3 )(R 3a ), —S(O) 2 N(R Z3 )(R 3a ), —(CR 1g R 1h ) u -G 2 , —(CR 1g R 1h ) u —CN, —(CR 1g R 1h ) u —O(R 1a ), and haloalkyl, two adjacent or non-adjacent atoms of each of said ring ark, optionally linked by an alkylene bridge or one, two, three, or four carbon atoms; and two substituents (R 21 ) on the same carbon atom, together with said carbon atom, optionally form a 3-6 membered monocyclic ring containing 0, 1, or 2 heteroatoms selected from O, S, or N(H);

R Za , at each occurrence, is independently hydrogen, alkyl, haloalkyl, —(CR c R d ) p —O(alkyl), G 1 , —(CR c R d ) q —CN, or —(CR c R d ) q -G 1 ;

R Zb , at each occurrence, is independently hydrogen, alkyl, haloalkyl, G 1 , or —(CR c R d ) q -G 1 ;

R Z1 , at each occurrence, is independently hydrogen, alkyl or haloalkyl;

R Z2a , at each occurrence, is independently hydrogen, alkyl,haloalkyl, G 1 , or —(CR c R d ) q -G 1 , or

R Z2b , at each occurrence, is independently hydrogen, alkyl, haloalkyl, G 1 , —C(O)R Zc , —C(O)OR Zc , —C(O)N(R Z1 )(R Zc ), —S(O) 2 R Zd , —S(O) 2 N(R Z1 )(R Zc ), or —(CR c R d ) q -G 1 ,R Zc , at each occurrence, is independently hydrogen, alkyl, haloalkyl, G 1 , or —(CR c R f ) t -G 1 ;

R Zd , at each occurrence, is independently alkyl, haloalkyl, G 1 , or —(CR c R f ) t -G 1 ;

G 1 , at each occurrence, is aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, wherein each G 1 is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, —CN, oxo, -G 2 , —NO 2 , —C(R Z3 )═N—O(R 1a ), —OR 1a , —O—(CR 1g R 1h ) u —CN, —OC(O)R 1a , —OC(O)N(R Z3 )(R 3a ), —O—(CR 1g R 1h ) u —CON(R Z3 )(R 3a ), —O—(CR 1g R 1h ) u —SO 2 N(R Z3 )(R 3a ), —SR 1a , —S(O) 2 ,R 2a , —S(O) 2 N(R Z3 )(R 3a ), —C(O)R 1a , —C(O)OR 1a , —C(O)N(R Z3 )(R 3a ), —N(R Z3 )(R 3a ), —N(R Z3 )C(O)R 1a , —N(R Z3 )S(O) 2 R 2a , —N(R Z3 )C(O)O(R 1a ), —N(R Z3 )C(O)N(R Z3 )(R 3a ), —(CR 1g R 1h ) u —NO 2 —(CR 1g R 1h ) u —OR 1a , —(CR 1g R 1h ) u —C(O)R 1a , —(CR 1g R 1h ) u —OC(O)N(R Z3 )(R 3a ), —(CR 1g R 1h ) u —SR 1a , —(CR 1g R 1h ) u —S(O) 2 R 2a , —(CR 1g R 1h ) u —S(O) 2 N(R Z3 )(R 3a ), —(CR 1g R 1h ) u —C(O)R 1a , —(CR 1g R 1h ) u —C(O)OR 1a , —(CR 1g R 1h ) u —C(O)N(R Z3 )(R 3a ), —(CR 1g R 1h ) u —N(R Z3 )(R 3a ), —(CR 1g R 1h ) u —N(R Z3 )C(O)R 1a , —(CR 1g R 1h ) u —N(R Z3 )S(O) 2 R 2a , —(CR 1g R 1h ) u —N(R Z3 )C(O)O(R 1a ), —(CR 1g R 1h ) u —N(R Z3 )C(O)N(R Z3 )(R 3a ), —(CR 1g R 1h ) u -G 2 , —(CR 1g R 1h ) u —CN, and haloalkyl;

R 1a and R 3a , at each occurrence, is independently hydrogen, alkyl, haloalkyl, G 2 , or —(CR k R x ) v -G 2 ;

R 2a , at each occurrence, is independently alkyl, haloalkyl, G 2 , or —(CR k R x ) v -G 2 ;

G 2 , at each occurrence, is aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, wherein each G 2 is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyd, alkenyl, alkynyl, halogen, —CN, oxo, —NO 2 , —OR 1b , —OC(O)R 1b , —OC(O)N(R Z4 )(R 3b ), —SR 1b , —S(O) 2 R 2b , —S(O) 2 ,N(R Z4 )(R 3b ), —C(O)R 1b , —C(O)OR 1b , —C(O)N(R Z4 )(R 3b ), —N(R Z4 )(R 3b ), —N(R Z4 )C(O)R 1b , —N(R Z4 )C(O)O(R 1b ), —N(R Z4 )C(O)N(R Z4 )(R 3 ), —(CR 2g R 2h ) w —NO 2 , —(CR 2g R 2h ) w —OR 1b , —(CR 2g R 2h ) w —OC(O)R 1b , —(CR 2g R 2h ) w —OC(O)N(R Z4 )(R 3b ), —(CR 2g R 2h ) w —SR 1b , —(CR 2g R 2h ) w —S(O) 2 R 2b , —(CR 2g R 2h ) w , —S(O) 2 N(R Z4 )(R 3b ), —(CR 2g R 2h ) w —C(O)R 1b , —(CR 2g R 2h ) w —C(O)OR 1b , —(CR 2g R 2h ) w —C(O)N(R Z4 )(R 3b ), —(CR 2g R 2h ) w —N(R Z4 )(R 3b ), —(CR 2g R 2h ) w —N(R Z4 )C(O)R 1b , —(CR 2g R 2h ) w —N(R Z4 )C(O)O(R 1b ), —(CR 2g R 2h ) w —N(R Z4 )C(O)N(R Z4 )(R 3b ), —(CR 2g R 2h ) w —CN, and haloalkyl;

m, q, t, u, v, and w, at each occurrence, are each independently 1, 2, 3, 4, or 5;

n and p, at each occurrence, are each independently 2, 3, 4, or 5;

R 1b and R 3b , at each occurrence, is independently hydrogen, alkyl, or haloalkyl;

R 2b , at each occurrence, is independently alkyl or haloalkyl;

R a , R c , R d , R e , R f , R 1g , R 1h , R 2g , R 2h , R k , and R x , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;

each occurrence of R 1p is independently hydrogen, halogen, alkyl, haloalky, or OH; and

R Z3 and R Z4 , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;

with the proviso that the compound is other than

4-methyl-N-[(3Z)-1-phenyl-1,4,5,6-tetrahydro-3H-cyclopenta[c]isothiazol-3-ylidene]benzenesulfonamide;

N-[(3Z)-1-cyclohexyl-4,5,6,7-tetrahydro-2,1-benzisothiazol-3(1H)-ylidene]-4-methylbenzenesulfonamide; or

4-methyl-N-[(3Z)-1-phenyl-4,5,6,7-tetrahydo-2,1-benzisothiazol-3(1H)-ylidene]benzenesulfonamide.

2. The method of claim 1 wherein the compound is selected from the group consisting of

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-(1,1-dimethylpropyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-cyclobutylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2,3-dimethylisothiazol-5(2H)-ylidene]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide:

N-[(5Z)-4-butyl-2-(1-methylcyclobutyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-allyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[(3-methyl-4,5-dihydroisoxazol-5-yl)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(cyclopropylmethyl)isothiazol-5(2H)-ylidene]-5chloro-2-methoxybenzamide;

N-[(3Z)-1-tert-butyl-5-propyl-4,5,6,7-tetrahydro-2,1benzisothiazol-3(1H)-ylidene]-5-chloro-2methoxybenzamide;

N-[(3Z)-1-tert-butyl-1,4,6,7-tetrahydro-3H-spiro[2,1-benzisothiazole-5,2′-[1,3]dioxolan]-3-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-hydroxyethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-methoxyethyl)isothiazol-5(2H)-ylidene]-5-chloro 2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-morpholin-4-ylethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[2-(5,5-dimethyl-1,3-dioxan-2-yl)ethyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-(2-azidoethyl)-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[(3E)-3-(methoxyimino)propy]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-(2-aminoethyl)-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[2-(dimethylamino)ethyl]isothiazol-5 (2H)-ylidene]-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-methylisothiazol-5(2H)-ylidene]-5 -chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(3-hydroxybutyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-cyanoethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2,3-dihydroxypropyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[(E)-(methoxyimino)methyl]isothiazol-5(2H)-ylidene]-5chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(1,3-dioxolan-2-ylmethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z) 2-text-butyl-4-(1-hydroxy-2-methylpropyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(cyanomethyl)isothiazol-5(2H)-ylidene]5-chloro-2-methoxybenzamide;

N-[(5Z)-4-[(1Z)-but-1enyl]-2-tert-butylisothiazol-5(2H)-yluidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-cyano-2-methoxybenzarnide;

N-[(5Z)-2-tert-butyl-4-(2-ethylcyclopropyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(hydroxymethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzaraide;

N-[(5Z)-2-tert-butyl-4-(methoxymethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzaimide;

N-[(5Z)-2-tert-butyl-4-(ethoxymethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(3-cyanopropyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[hydroxy(phenyl)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybezamide;

N-[(5Z)-4-(azidomethyl)-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-cyclobutyl-1-hydroxyethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-buty4-[cyclobutyl(hydroxy)methyl]isothiazol-5(2H)ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-benzyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-cyclobutylethyl)isothiazol-5(2 H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-isobutylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(cyclobutylmethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-tetrahydro-2H-pyran-4-ylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[hydroxy(1,3-thiazol-2-yl)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2,5-dimethoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-fluoro-2 -methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxy-5-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[hydroxy(thien-2-yl)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

methyl 4-{(5Z)-2-tert-butyl-5-[(5-chloro-2-methoxybenzoyl)imino]-2,5-dihydroisothiazol-4-yl}butanoate;

methyl 4-{(5Z)-2-tert-butyl-5-[(5-cyano-2-methoxybenzoyl)imino]-2,5-dihydroisothiazol-4-yl}butanoate;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-fluorobenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-(2,2,2-trifluoroethoxy)benzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxy-5-(methylsulfonyl)benzamide;

N-[(5Z)-2-test-butyl-4-[hydroxy(1,3-thiazol-4-yl)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-furylmethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(2-furylmethyl)isothiazol-5(2H)-ylidene]-5-cyano-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(1,3-thiazol-4-ylmethyl)isothiazol-5(2H)ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(thein-2-ylmethyl)isothiazol-5(2H)-ylidene]-5-cyano-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(thien-2-ylmethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

5-amino-N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H) ylidene]-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-formyl-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxy-5-[(E)-(methoxyimino)methyl]benzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-(formylamino)-2-methoxybenzarmide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-[(E)-(hydroxyimino)methyl]-2-methoxybenzamide;

3-({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]amino}carbonyl)-4-methoxybenzoic acid;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-iodo-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-ethynyl 2methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethoxy)benzamide;

5-acetyl-N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-(difluoromethyl)-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-(fluoromethyl)-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(tetrahydro furan-2-ylmethyl)isothiazol-5 (2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-[(1Z)-N-hydroxyethanimidoyl]-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-(1,1-difluoro ethyl)-2-methoxybenzamide;

N-[(5Z)-2-text-butyl-4-(2-furylmethyl)isothiazol-5(2H)-ylidene]-2fluoro-3-(trifluoromethyl)benzamide;

N-[(5Z)-2-tert-butyl-4-(2-furylmethyl)isothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-2-tert-butyl-4-(isopropoxymethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-fluoro-3-(trifluoromethyl)benzamide;

methyl 3-({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-yldene]amino }carbonyl)-4-methoxybenzoate;

N-[(5Z)-2-tert-butyl-4-(4-oxopentyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-oxopentyl)isothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-2-tert-butyl-4-(4-oxopentyl)isothiazol-5(2H)-ylidene]-2- fluoro-3-(trifluoromethyl)benzamide;

N 3 -[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-4-methoxyisophthalamide;

N-[(5Z)-2-tert-butyl-4-(4-hydroxy-4-methylpentyl)isothiazol-5(2H)-ylidene]-2-fluoro-3-(trifluoromethyl)benzamide;

N-[(5Z)-2-tert-butyl-4-(4-hydroxy-4-methylpentyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-hydroxy-4-methylpentyl)isothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-isopropyl-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-fluoro-4-methylpentyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(3-oxobutyl)isothiazol-5(2H)-ylidene]-5-chluoro-2 -methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[(2,2,2-trifluoroethoxy)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4,4-difluoropentyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(3-fluoro-3-methylbutyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-fluoro-4-methylpentyl)isothiazol-5(2 Z)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-2-tert-butyl-4-{[(2R)-tetrahydrofuran-2-ylmethoxy]methyl}isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[(2-fluoroethoxy)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-[(2,2-difluoroethoxy)methyl]isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

methyl 3-({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]amino}carbonyl)-2,2,3-trimethylcyclopentanecarboxylate;

methyl 3-({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]amino}catbonyl)-1,2,2-trimethylcyclopentanecarboxylate;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-1-phenylcyclobexancarboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-1(2-chloro-4-fluorophenyl)cyclohexanecarboxamide;

3-({[(5Z)-4-butyl-2-tert-butylisothiazol-5-(2H)-ylidene]amino}carbonyl) 2,2,3-trimethylcyclopentanecarboxylic acid;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-3-oxocyclopentanecarboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-1-phenylcyclopentanecarboxamide;

N 1 -[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-N 3 , N 3 , 1,2,2-pentamethylcyclopentane-1,3-dicarboxamide;

N 1 -[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-N 3 ,1,2,2-tetramethylcyclopentane-1,3-dicarboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-3-[3,3-difluoro azetidin-1-yl)carbonyl]-1,2,2-trimethylcyclopentanecarboxamide;

(1S,4R)-N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide;

(1R,4 S)-N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide;

ethyl 3-({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]amino}carbonyl)pyrrolidine-1-carboxylate;

3-({[(5Z)-4-butyl-2-tert-butylisothizol-5(2H)-ylidene]amino}carbonyl)-1,2,2-trimethylcyclopentanecarboxylic acid;

tert-butyl 3({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]amino}carbonyl)pyrrtolidine-1-carboxylate;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-1-(3-cyanopyridin-2-yl)pyrrolidine-3-carboxamide;

methyl 4-({[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]amino}carbonyl)bicyclo[2,2,2]octane-1-carboxylate;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-oxo-1-phenylpyrrolidine-3-carboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-N′-cyano-2-methoxybenzenecarboximidamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5chloro-2-methoxybenzenecarbothioamide;

N-[(3Z)-1-tert-butyl-5-(trifluoromethyl)-4,5,6,7-tetrahydro-2,1-benzisothiazol-3(1H)-ylidene]-5-chloro-2-methoxybenzaniide;

tert-butyl (3Z)-1-tert-butyl-3-[(5-chloro-2-methoxybenzoyl)imino]-1,4,6,7-tetrahydroisothiazolo[4,3-c]pyridine-5(3H)-carboxylate;

N-[(3Z)-1-tert-butyl-4,5,6,7-tetrahydroisothiazolo[4,3-c]pyridin-3(1H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzenesulfonamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]naphthalene-1sulfonamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-(dimethylamino)naphthalene-1-sulfonamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]cyclohexanesulfonamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]benzenesulfonamide;

N-[(5Z)-4-butyl 2-tert-butylisothiazol-5(2H)-ylidene]quinoline-8-sulfonamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2,2,3,3-tetramethylcyclopropanecarboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2,3-dichlorobenzenesulfonamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]adamantane-1-carboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-N′-cyano-2-methoxy-5-(trifluoromethyl)benzenecarboximidamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2,2-dimethyl-4-oxo-3,4-dihydro-2H-pyran-6-carboxamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-N′-cyano-2-ethoxy-5(trifluoromethyl)benzenecarboximidamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzarnide;

N-[(5Z)-2-tert-butyl-4-(3cyanopropyl)isothiazol-5(2H)-ylidene]-5-chloro-N′-cyano-2-methoxybenzenecarboximidamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-cyano-2-hydroxybenzarnide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-cyano-2-(2,2,2-trifluoroethoxy)benzamide;

N-[(5Z)-2-tert-butyl-4-(3-cyanopropyl)isothiazol-5(2H)-ylidene]-5-cyano-2-(2,2,2-trifluoroethoxy)benzamide;

N-[(5Z)-2-tert-butyl-4-(3-cyanopropyl)isothiazol-5(2H)-ylidene]-5-cyano-2-hydroxybenzamide;

N-[(5Z)-2-tert-butyl-4-(3-cyanopropyl)isothiazol-5(2H)-ylidene]-5-chloro-2-(2,2,2-trifluoroethoxy)benzamide;

N-[(5Z)-2-tert-butyl-4-(3-cyanopropyl)isothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-hydroxybenzamide;

N-[(5Z)-2-tert-butyl-4-(cyclopentylmethyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(3-cyano-3-methylbutyl)isothiazol-5(2H)-yliden]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-cyanobutypisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]5-chloro-2-(2-fluoroethoxy)benzamide;

2-(2-amino-2-oxoethoxy)-N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chlorobenzamide;

2-(2-amino-2-oxoethoxy)-N-[(5Z)-2-tert-butyl-4-(3-cyanopropyl)isothiazol-5(2H)-ylidene]-5-chlotobenzamide;

N-[(5Z)-2-tert-butyl-4-(4,4,4-trifluorobutyl)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenazanide;

N-[(5Z)-2-tent-butyl-4-isobutylisothiazol-5(2H)-yliden]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-test-butyl-4-isobutylisothiazol-5(2H)-ylidene]-5-chloro-2-(2-fluoroethoxy)benzamide;

N-[(5Z)-2-tert-butyl-4-isobutylisothiazol-5(2H)-ylidene]-5-cyano-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-isobutylisothiazol-5(2H)-ylidene]-2-ethoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-2-tert-butyl-4-pentylisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-fluorobutyl)isothiazol-5(2H)-ylidene]-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-fluorobutyl)isothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidene]-5-chloro-2-[2-(dimethylamino)-2-oxoethoxy]benzamide;

N-[(5Z)-4-butyl-2-(2,2,2-trifluoro-1,1-dimethylethyl)isothiazol-5(2H)-ylidenel]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4-butyl-2-(2-fluoro-1,1-dimethylethyl)isothiazol-5(2H)ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

N-[(5Z)-4-butyl-2-tert-butylisothiazol-5(2H)-ylidenel]-5-chloro-2-(cyanomethoxy)benzamide;

N-[(5Z)-4-butyl 2 (2-fluoro-1,1 -dimethylethyl)isothiazol- 5-(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-4(benzyloxy)-2-tert butylsothiazol-5(2H)-ylidene]-5-chloro-2-methoxvbenzamide;

N-[(5Z)-2-tert-butyl-4-hydroxyisothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(1-methylpropoxy)isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(1-methylpropoxy)isothiazol-5(2H)-ylidene]5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-(4-fluorobutoxy)isothiazol-5(2 H)-ylidene]-5-chloro-2-methoxybenzarnide;

N-[(5Z)-2-tert-butyl-4-(cyanomethoxy)isothiazol-5-(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2tert-butyl-4-{[(25)-5-oxopyrrolidin-2-yl]methoxy}isothiazol-5(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(5Z)-2-tert-butyl-4-{[(2R)-5-oxopyrrolidin-2-yl]methoxy}isothiazol-5(2H)-ylidene]5-chloro-2-methoxybenzamide; and

tert-butyl[(5Z)-2-tert-butyl-5-{[(5-chloro-2-methoxyphenyl)carbonyl]imino}-3-methyl-2,5-dihydroisothiazol-4-yl]carbamate, or a pharmaceutically acceptable salt thereof.