Fluorene compound and pharmaceutical use thereof

Abstract

wherein each symbol is as defined in the specification.

1 - 2 . (canceled) 
     
     
         3 . A method for the prophylaxis of diabetes, diabetic complications, insulin resistance syndrome, metabolic syndrome, hyperglycemia, dyslipidemia, atherosclerosis, cardiac failure, cardiomyopathy, myocardial ischemia, brain ischemia, cerebral apoplexy, pulmonary hypertension, hyperlactacidcemia, mitochondrial disease, mitochondrial encephalomyopathy or cancer in a mammal, comprising administering to the mammal a pharmaceutically effective amount of a compound [I] or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         R a  is: 
         (1) a hydrogen atom, or 
         (2) a halogen atom; 
         R b  is: 
         (1) a hydrogen atom, 
         (2) a halogen atom, 
         (3) a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from a group A, 
         (4) a C 2-6  alkenyl group optionally substituted by the same or different 1 to 5 substituents selected from a group C, 
         (5) a C 2-6  alkynyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (6) a cyano group, 
         (7) —C(═O)—R b1 , wherein R b1  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from a group B, 
         (8) —C(═O)—OR b2 , wherein R b2  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (9) —C(═O)—NR b3 R b4 , wherein R b3  and R b4  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (10) —C(═O)—NR b5 —OR b6 , wherein R b5  and R b6  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (11) —OR b7 , wherein R b7  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (12) —NR b8 R b9 , wherein R b8  and R b9  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (13) —NR b10 —C(═O)—R b11 , wherein R b10  and R b11  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (14) —NR b12 —C(═O)—OR b13 , wherein R b12  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group, and R b13  is a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (15) —O—C(═O)—NR b14 R b15 , wherein R b14  and R b15  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, or 
         (16) a group represented by formula: 
       
       
         
           
           
               
               
           
         
         wherein: 
         Y b  is: 
         (i) a single bond, 
         (ii) a C 1-6  alkylene, 
         (iii) a C 2-6  alkenylene, 
         (iv) —O—(CH 2 ) n1 —, wherein n1 is an integer of 0, or 1 to 4, 
         (v) —O—(CH 2 ) n2 —C(═O)—, wherein n2 is an integer of 0, or 1 to 4, 
         (vi) —C(═O)—, or 
         (vii) —NR b16 —, wherein R b16  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B; 
         ring T is: 
         (i) a C 6-10  aryl group, 
         (ii) a C 3-10  cycloalkyl group, 
         (iii) a C 5-10  bridged cycloalkyl group, 
         (iv) a monocyclic aromatic heterocyclic group which contains, besides carbon atom, 1 to 4 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and has 3 to 7 ring-constituting atoms, or 
         (v) a monocyclic non-aromatic heterocyclic group which contains, besides carbon atom, 1 to 4 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and has 3 to 7 ring-constituting atoms, 
         R j  are the same or different and each is a substituent selected from a group D, and p is an integer of 0, or 1 to 4; 
         R c  is: 
         (1) a hydrogen atom, 
         (2) a halogen atom, 
         (3) a C 1-6  alkyl group, 
         (4) —C(═O)—OR c1 , wherein R c1  is a hydrogen atom or a C 1-6  alkyl group, 
         (5) —OR c2 , wherein R c2  is a hydrogen atom or a C 1-6  alkyl group, 
         (6) —NR C3 R c4 , wherein R C3  and R c4  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group, or 
         (7) —NR c5 —C(═O)—R c6 , wherein R c5  and R c6  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group; 
         X d  is: 
         a nitrogen atom; 
         R e  are the same or different and each is: 
         (1) a halogen atom, or 
         (2) a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C; and 
         n is an integer of 0, or 1 to 3, 
         wherein the Group A is selected from the group consisting of: 
         (a) a halogen atom, 
         (b) a cyano group, 
         (c) —C(═O)—R A1 , wherein R A1  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (d) —C(═O)—OR A2 , wherein R A2  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (e) —C(═O)—NR A3 R A4 , wherein R A3  and R A4  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (f) —C(═O)—NR A5 —OR A6 , wherein R A5  and R A6  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (g) —OR A7 , wherein R A7  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, 
         (h) —NR A8 R A9 , wherein R A8  and R A9  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (i) —NR A10 —C(═O)—R A11 , wherein R A10  and R A11  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (j) —NR A12 —C(═O)—OR A13 , wherein R A12  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, and R A13  is a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (k) —S(═O) 2 —R A14 , wherein R A14  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, 
         (l) —S(═O) 2 —OR A15 , wherein R A15  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group B, and 
         (m) —Si—(CH 2 —CH 3 ) 3 , 
         wherein the Group B is selected from the group consisting of: 
         (a) a halogen atom, 
         (b) a cyano group, 
         (c) —C(═O)—R B1 , wherein R B1  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (d) —C(═O)—OR B2 , wherein R B2  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (e) —C(═O)—NR B3 R B4 , wherein R B3  and R B4  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group C, 
         (f) —C(═O)—NR B5 —OR B6 , wherein R B5  and R B6  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (g) —OR B7  wherein R B7 , is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (h) —NR B8 R B9 , wherein R B8  and R B9  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (i) —NR B10 —C(═O)—R B11 , wherein R B10  and R B11  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (j) —NR B12 —S(═O) 2 —R B3 , wherein R B12  and R B13  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (k) —NR B14 —C(═O)—OR B5 , wherein R B14  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group C, and R B15  is a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         (l) —S(═O) 2 —R B6 , wherein R B16  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, and 
         (m) —S(═O) 2 —OR B17 , wherein R B17  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group C, 
         wherein the Group C is selected from the group consisting of: 
         (a) a halogen atom, 
         (b) —C(═O)—R C1 , wherein R C1  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 halogen atoms, 
         (c) —C(═O)—OR C2 , wherein R C2  is a hydrogen atom or a C 1-6  alkyl group, and 
         (d) —OR C3 , wherein R C3  is a hydrogen atom or a C 1-6  alkyl group, 
         wherein the Group D is selected from the group consisting of: 
         (a) a halogen atom, 
         (b) a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from a group E, 
         (c) a C 1-6  alkyl group substituted by a C 6-10  aryl group optionally substituted by the same or different 1 to 5 substituents selected from a group F, 
         (d) a C 1-6  alkyl group substituted by a C 3-10  cycloalkyl optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (e) a C 1-6  alkyl group substituted by a C 5-10  bridged cycloalkyl optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (f) a C 1-6  alkyl group substituted by a monocyclic aromatic heterocyclic group optionally substituted by the same or different 1 to 5 C 1-6  alkyl groups, the monocyclic aromatic heterocyclic group containing 1 to 4 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and has 3 to 7 ring-constituting atoms, 
         (g) a C 3-10  cycloalkyl group optionally substituted by the same or different 1 to 5 substituents selected from a group F, 
         (h) a C 5-10  bridged cycloalkyl group optionally substituted by the same or different 1 to 5 substituents selected from group F, 
         (i) a cyano group, 
         (j) —C(═O)—R D1 , wherein R D1  is a hydrogen atom, a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, or a monocyclic non-aromatic heterocyclic group optionally substituted by the same or different 1 to 5 substituents selected from the group F, the monocyclic non-aromatic heterocyclic group containing 1 to 4 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and has 3 to 7 ring-constituting atoms, 
         (k) —C(═O)—OR D2 , wherein R D2  is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (l) —C(═O)—NR D3 R D4 , wherein R D3  and R D4  are the same or different and each is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (m) —C(═O)—NR D5 —OR D6 , wherein R D5  and R D6  are the same or different and each is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (n) —OR D7 , wherein R D7  is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (o) —NR D8 R D9 , wherein R D8  and R D9  are the same or different and each is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (p) —NR D10 —C(═O)—R D11 , wherein R D10  and R D11  are the same or different and each is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (q) —NR D12 —C(═O)—OR D13 , wherein R D12  is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, and R D13  is a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         (r) —S(═O) 2 —R D14 , wherein R D14  is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, and 
         (s) —S(═O) 2 —OR D15 , wherein R D15  is a hydrogen atom, or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group E, 
         wherein the Group E is selected from the group consisting of: 
         (a) a halogen atom, 
         (b) a cyano group, 
         (c) —C(═O)—R E1 , wherein R E1  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (d) —C(═O)—OR E2 , wherein R E2  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (e) —C(═O)—NR E3 R E4 , wherein R E3  and R E4  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (f) —C(═O)—NR E5 —OR E6 , wherein R E5  and R E6  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (g) —OR E7 , wherein R E7  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (h) —NR E8 R E9 , wherein R E8  and R E9  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (i) —NR E10 —C(═O)—R E11 , wherein R E10  and R E11  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (j) —NR E12 —C(═O)—OR E13 , wherein R E12  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group F, and R E13  is a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (k) —S(═O) 2 R E14 , wherein R E14  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, 
         (l) —S(═O) 2 —OR E15 , wherein R E15  is a hydrogen atom or a C 1-6  alkyl group optionally substituted by the same or different 1 to 5 substituents selected from the group F, and 
         (m) —NR E16 —S(═O) 2 —R E17 , wherein R E16  and R E17  are the same or different and each is a hydrogen atom or a C 1-6  alkyl group, and 
         wherein the Group F is selected from the group consisting of: 
         (a) —(CH 2 ) nF1 —C(═O)—OR F1 , wherein R F1  is a hydrogen atom or a C 1-6  alkyl group, and nF1 is an integer of 0, or 1 to 4, and 
         (b) —(CH 2 ) nF2 —OR F2 , wherein R F2  is a hydrogen atom or a C 1-6  alkyl group, and nF2 is an integer of 0, or 1 to 4.