Substituted arylalkanoic acid derivatives and use thereof

Abstract

A compound represented by the formula (I): [In the formula, Link represents a saturated or unsaturated straight hydrocarbon chain having 1 to 3 carbon atoms, C 2 to C 6 in the aromatic ring (E) independently represent a ring-constituting carbon atom, one of the ring-constituting carbon atoms may be replaced with V, V represents nitrogen atom, or carbon atom substituted with Zx, Zx represents a saturated alkyl group having 1 to 4 carbon atoms and the like, Rs represents -D-Rx etc., D represents a single bond, oxygen atom and the like, Rx represents a saturated alkyl group having 3 to 8 carbon atoms and the like, AR represents a partially unsaturated or completely unsaturated condensed bicyclic carbon ring or a heterocyclic ring, and Y represents hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms and the like] or a salt thereof. A compound having prostaglandin production-suppressing action and leukotriene production-suppressing action is provided.

1 . A compound represented by the following formula (II): 
     
       
         
         
             
             
         
       
     
     in the formula, each of C 2 ′, C 3 ′, C 4 ′, C 5 ′, and C 6 ′ in the aromatic ring (E′) represents a ring-constituting carbon atom, any one of them to which Rs′ and G does not bind may be replaced with V′,
 V′ represents nitrogen atom, or carbon atom substituted with Zx′, Zx′ has the same meaning as Zx mentioned above, provided that when Zx contains hydroxyl group, the hydroxyl group may be protected with Rp 1 , and when Zx contains amino group, the amino group may be protected with Rp 2 , 
 Rs′ represents -D-Rx′ or —N(Ry′)(Rz′), 
 -D-Rx′ and —N(Ry′)(Rz′) have the same meanings as -D-Rx and —N(Ry)(Rz), respectively, provided that when -D-Rx or —N(Ry)(Rz) contains hydroxyl group, the hydroxyl group may be protected with Rp 1 , when -D-Rx or —N(Ry)(Rz) contains amino group, the amino group may be protected with Rp 2 , 
 G represents chlorine atom, bromine atom, iodine atom, mesylate group, triflate group, or an arenesulfonate group of which aromatic portion may be substituted with one of T 1  or two or more of the same or different T 1 , and 
 Y′ represents a lower alkyl group having 1 to 4 carbon atoms. 
 
   
   
       2 . The compound according to  claim 1 , wherein, in the formula (II), n is an integer of 2, G binds to C 3 ′ in the aromatic ring (E′), Rs′ binds to C 4 ′ in the aromatic ring (E′), C 5 ′ is carbon atom substituted with —N(Rn 1 )(Rn 2 ) group (provided that one of Rn 1  and Rn 2  is a substituent other than hydrogen atom), C 2 ′ and C 6 ′ are unsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′. 
   
   
       3 . The compound according to  claim 1 , wherein, in the formula (II), n is an integer of 2,
 C 3 ′ is carbon atom to which G binds, C 4 ′ is carbon atom to which Rs′ binds, C 5 ′ is carbon atom substituted with Zx′, C 2 ′ and C 6 ′ are unsubstituted ring-constituting carbon atoms,   Zx′ is N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N,N-dimethylamino group, N,N-diethylamino group, formylamino group, acetylamino group, carbamoylamino group, mesylamino group, or N,N-dimethylsulfamoylamino group, provided that when Zx′ contains amino group, the amino group may be protected with Rp 2 ,   Rs′ is —O-Rx′, Rx′ is butyl group, isobutyl group, 2-ethylbutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-methylphenyl group, 4-methylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, indan-2-yl group, 4-methylindan-2-yl group, 5-methylindan-2-yl group, 4,7-dimethylindan-2-yl group, 5,6-dimethylindan-2-yl group, 4-fluoroindan-2-yl group, 5-fluoroindan-2-yl group, 4,7-difluoroindan-2-yl group, 5,6-difluoroindan-2-yl group, 4-chloroindan-2-yl group, 5-chloroindan-2-yl group, 4,7-dichloroindan-2-yl group, 5,6-dichloroindan-2-yl group, 4-methoxyindan-2-yl group, 5-methoxyindan-2-yl group, 4,7-dimethoxyindan-2-yl group, 5,6-dimethoxyindan-2-yl group, 1-phenylethyl group, 1-(2-fluorophenyl)ethyl group, 1-(3-fluorophenyl)ethyl group, 1-(4-fluorophenyl)ethyl group, 1-(2-chlorophenyl)ethyl group, 1-(3-chlorophenyl)ethyl group, 1-(4-chlorophenyl)ethyl group, 2-methylphenylmethyl group, 3-methylphenylmethyl group, 4-methylphenylmethyl group, 2,3-dimethylphenylmethyl group, 3,5-dimethylphenylmethyl group, 2-fluorophenylmethyl group, 3-fluorophenylmethyl group, 4-fluorophenylmethyl group, 2-chlorophenylmethyl group, 3-chlorophenylmethyl group, 4-chlorophenylmethyl group, 2,3-difluorophenylmethyl group, 2,4-difluorophenylmethyl group, 2,5-difluorophenylmethyl group, 3,4-difluorophenylmethyl group, 2,3-dichlorophenylmethyl group, 2,4-dichlorophenylmethyl group, 2,5-dichlorophenylmethyl group, 2,6-dichlorophenylmethyl group, 3,4-dichlorophenylmethyl group, 3,5-dichlorophenylmethyl group, 3,6-dichlorophenylmethyl group, 2-(trifluoromethyl)phenylmethyl group, 3-(trifluoromethyl)phenylmethyl group, 4-(trifluoromethyl)phenylmethyl group, 2-(2-methylphenyl)ethyl group, 2-(3-methylphenyl)ethyl group, 2-(4-methylphenyl)ethyl group, 2-(2-methoxyphenyl)ethyl group, 2-(3-methoxyphenyl)ethyl group, 2-(4-methoxyphenyl)ethyl group, 2-(2-fluorophenyl)ethyl group, 2-(3-fluorophenyl)ethyl group, 2-(4-fluorophenyl)ethyl group, 2-(2-chlorophenyl)ethyl group, 2-(3-chlorophenyl)ethyl group, 2-(4-chlorophenyl)ethyl group, 2-[2-(trifluoromethyl)phenyl]ethyl group, 2-[3-(trifluoromethyl)phenyl]ethyl group, 2-[4-(trifluoromethyl)phenyl]ethyl group, 2-[4-(N,N-dimethylamino)phenyl]ethyl group, 2-phenyloxyethyl group, 2-(2-chlorophenyloxy)ethyl group, 2-(3-chlorophenyloxy)ethyl group, 2-(4-chlorophenyloxy)ethyl group, 2-(phenylthio)ethyl group, 2-(N-phenyl-N-methylamino)ethyl group, or 2-(N-ethyl-N-phenylamino)ethyl group,   G is bromine atom or iodine atom, and   Y′ is methyl group or ethyl group.   
   
   
       4 . The compound according to  claim 1 , wherein, in the formula (II), G binds to C 3 , in the aromatic ring (E′), Rs′ binds to C 4 ′ in the aromatic ring (E′), C 5 ′ is a ring-constituting carbon atom substituted with Zx′, or an unsubstituted ring-constituting carbon atom, C 2 ′ and C 6 ′ are unsubstituted ring-constituting carbon atoms, Rs′ is —O-Rx′, and Rx′ is a linear or branched saturated alkyl group having 3 to 8 carbon atoms, or Ra or Rb. 
   
   
       5 . The compound according to  claim 1 , wherein, in the formula (II), n is an integer of 2, G binds to C 3 ′ in the aromatic ring (E′), Rs′ binds to C 4 ′ in the aromatic ring (E′), C 5 ′ is carbon atom substituted with nitro group, C 2 ′ and C 6 ′ are unsubstituted ring-constituting carbon atoms, and Rs′ is —O-Rx′.