Thiazolidine derivatives and medicinal use thereof

1. A thiazolidine derivative represented by the formula (I):

wherein X is a substituent of the following formula:

wherein

m is an integer of 1,

is a single bond or a double bond,

A is a carbon atom or a nitrogen atom,

wherein i) when A is a carbon atom, then A is optionally substituted by a hydroxyl group, carboxy or alkoxycarbonyl, and ii) when A is a nitrogen atom, then

is a single bond, and

Q is aryl or heteroaryl selected from the compounds represented by the following formulas (II)-(XII):

wherein

(i) in the formula (II), 1 to 3 from a, b, c and d is(are) nitrogen atom(s) and the rest is(are) carbon atom(s) or all of them are nitrogen atoms,

R 1a is alkyl, phenyl, pyridyl, pyrimidinyl, imidazolyl or oxazolyl, wherein these groups are optionally substituted by one or more from alkyl, alkoxy, halogen and cyano,

R 2a is a hydrogen atom, alkyl or haloalkyl,

wherein

(i-1) when b is a nitrogen atom, then R 2a is not present,

(i-2) when c and d are both nitrogen atoms, a and b are both carbon atoms, R 1a is phenyl and R 2a is alkyl, then R 1a has one or more substituents mentioned above,

(i-3) when a and d are both nitrogen atoms, b and c are both carbon atoms and R 1a is phenyl without substituent, then R 2a is alkyl or haloalkyl, and

(i-4) when all of a, b, c and d are nitrogen atoms and R 1a is phenyl, then (1) A of the formula (I-b) is a carbon atom and R 1a does not have the above-mentioned substituent, or (2) R 1a is substituted by one or more from alkyl and halogen,

(ii) in the formula (III), one of e and f is a nitrogen atom and the other is a carbon atom, or both are carbon atoms, and

R 3 and R 4 may be the same or different and each is a hydrogen atom, alkyl, phenyl or pyridyl,

(iii) in the formula (IV), j is a sulfur atom, an oxygen atom or a nitrogen atom,

h and i may be the same or different and each is a nitrogen atom or a carbon atom,

R 5 and R 7 may be the same or different and each is a hydrogen atom, phenyl or pyridyl (when h is a nitrogen atom, then R 7 is absent), and

R 6 is a hydrogen atom or alkyl (when i is a nitrogen atom, then R 6 is absent),

(iv) in the formula (V), k, l and n′ may be the same or different and each is a carbon atom or a nitrogen atom, wherein at least one is a carbon atom,

R 8 is a hydrogen atom, phenyl, pyridyl or nitro (when n′ is a nitrogen atom, then R 8 is absent),

R 8a is a hydrogen atom or phenyl,

R 9 is a hydrogen atom, haloalkyl or cyano, and

R 10 is a hydrogen atom or cyano (when 1 is a nitrogen atom, then R 10 is absent),

wherein

(iv-1) when k and n′ are both nitrogen atoms, (1) A of the formula (I-b) is a nitrogen atom, and R 8a , R 9 and R 10 are all hydrogen atoms, or (2) R 8a is phenyl and R 9 is haloalkyl,

(iv-2) when k, l and n′ are all carbon atoms, then R 8 is phenyl or pyridyl,

(iv-3) when k is a nitrogen atom and 1 and n′ are both carbon atoms, (1) R 8 is phenyl or nitro, or (2) R 9 is cyano, and

(iv-4) when 1 is a nitrogen atom, then one of k and n′ is a nitrogen atom,

(v) in the formula (VI), p is a nitrogen atom or a carbon atom,

R 11 is a hydrogen atom, phenyl or pyridyl (when p is a nitrogen atom, then R 11 is phenyl or pyridyl),

R 12 is a hydrogen atom or alkyl (when p is a nitrogen atom, then R 12 is absent), and

R 13 and R 14 are both hydrogen atoms, or when one of them is a hydrogen atom, then the other is cyano, alkoxy or halogen,

(vi) in the formula (VII), one of r and s is a nitrogen atom and the other is a carbon atom,

R 15 is a hydrogen atom, alkyl or phenyl (when r is a nitrogen atom, then R 15 is absent),

R 16 is a hydrogen atom or alkyl (when s is a nitrogen atom, then R 16 is absent), and

R 17 is a hydrogen atom, haloalkyl or cyano,

(vii) in the formula (VIII), r′ and s′ may be the same or different and each is a carbon atom or a nitrogen atom, wherein at least one of them is a nitrogen atom,

R 15a is a hydrogen atom, alkyl or phenyl (when r′ is a nitrogen atom, then R 15a is absent),

R 16a is a hydrogen atom or alkyl (when r′ and s′ are both nitrogen atoms, then R 16a is a hydrogen atom), and

R 17a is a hydrogen atom, haloalkyl or cyano,

(viii) in the formula (IX), t is a sulfur atom or an oxygen atom,

u is a carbon atom or a nitrogen atom, and

R 18 and R 19 are both hydrogen atoms, or one of them is a hydrogen atom and the other is cyano, alkoxy or halogen,

wherein

(viii-1) when u is a carbon atom, then one of R 18 and R 19 is cyano, alkoxy or halogen,

(viii-2) when t is a sulfur atom, then A in the formula (I-b) is a carbon atom, R 19 is a hydrogen atom and R 18 is methoxy or cyano,

(viii-3) A in the formula (I-b) is a nitrogen atom, t is an oxygen atom, R 19 is a hydrogen atom, and when u is a carbon atom, then R 18 is alkoxy or halogen, and

(viii-4) A in the formula (I-b) is a carbon atom, R 19 is a hydrogen atom, u is a carbon atom, and when t is an oxygen atom, R 18 is halogen,

(ix) in the formula (X), v, w, x and y may be the same or different and each is a carbon atom or a nitrogen atom, wherein at least two are carbon atoms,

R 20 , R 21 , R 22 , R 23 , R 24 , R 25 and R 26 may be the same or different and 1 to 3 is(are) haloalkyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, hydroxy, cyano or halogen, and the rest is(are) hydrogen atom(s) (when v is a nitrogen atom, then R 20 is absent, when w is a nitrogen atom, then R 22 is absent, when x is a nitrogen atom, then R 23 is absent, when y is a nitrogen atom, then R 25 is absent),

wherein

(ix-1) when v is a nitrogen atom and w, x and y are all carbon atoms, then R 22 is haloalkyl,

(ix-2) when v and w are both nitrogen atoms and x and y are both carbon atoms, then R 21 is cyano, and

(ix-3) when w is a nitrogen atom and v, x and y are all carbon atoms, then (1) R 21 is a hydrogen atom and R 20 is cyano, (2) R 21 is haloalkyl and R 23 is hydroxy, ethoxy, isopropoxy, trifluoromethoxy or 2,2,2-trifluoroethoxy, (3) R 21 is haloalkyl and R 23 and R 25 are both methoxy, (4) R 21 is haloalkyl and R 24 is hydroxy, chloro or trifluoromethyl, (5) R 21 is haloalkyl and R 25 is hydroxy or trifluoromethoxy, (6) R 21 is haloalkyl and R 26 is methoxy, or (7) R 21 is cyano and R 23 is methoxy, and

(x) in the formula (XI), R 27 and R 28 may be the same or different and each is haloalkyl or alkoxy;

Y is methylene, hydroxymethylene, a sulfur atom, sulfinyl or sulfonyl; and

Z is a hydrogen atom or cyano;

wherein when X is a substituent represented by the formula (I-a), then Z is a hydrogen atom, or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising the thiazolidine derivative of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmacologically acceptable carrier.

3. A method of inhibiting DPP-IV, which method comprises administering the thiazolidine derivative of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof, whereupon DPP-IV is inhibited.

4. A method of treating type 2 diabetes, which method comprises administering the thiazolidine derivative of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof, whereupon type 2 diabetes is treated.

5. A method of treating obesity, which method comprises administering the thiazolidine derivative of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof, whereupon obesity is treated.