Aromatic amine derivatives, their production and use

1. A Compound of the following formula, or a salt thereof:

wherein Ring A represents an optionally-substituted benzene ring;

Ring B represents an optionally-substituted benzene or cycloalkane ring;

Z represents an optionally-substituted cyclic hydrocarbon group or an optionally-substituted heterocyclic group;

R 1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, or an acyl group;

R 2 represents an optionally-substituted amino group;

D is an optionally substituted C 1-6 alkylene group;

E represents —CON(R a )—

wherein R a represents a hydrogen atom or an optionally-substituted C 1-6 alkyl group;

G represents an optionally substituted C 1-6 alkylene group;

L represents an alkylene group optionally having from 1 to 5 substituents selected from;

(i) a C 1-6 alkyl group,

(ii) a halogeno-C 1-6 alkyl group,

(iii) a phenyl group,

(iv) a benzyl group,

(v) an optionally-substituted amino group,

(vi) an optionally-substituted hydroxy group, and

(vii) a carbamoyl or thiocarbamoyl group optionally substituted by:

<1> a C 1-6 alkyl group,

<2> an optionally-substituted phenyl group, or

<3> an optionally-substituted heterocyclic group;

X represents an oxygen atom or an optionally-oxidized sulfur atom; and

Y represents two hydrogen atoms.

2. A Compound as claimed in claim 1 , wherein L is an alkylene group optionally substituted by a C 1-6 alkyl group.

3. A Compound as claimed in claim 1 , wherein L is a C 1-6 alkylene group.

4. A Compound as claimed in claim 1 , wherein R 2 is (1) an unsubstituted amino group, or (2) an amino group optionally having one or two substituents selected from (i) a benzyl group, (ii) a C 1-6 alkyl group optionally substituted by an amino or phenyl group, (iii) a (mono- or di-C 1-6 alkyl)-carbamoyl or -thiocarbamoyl group, (iv) a C 1-6 alkoxy-carbonyl group, (v) a C 1-6 alkyl-sulfonyl group, (vi) a piperidylcarbonyl group, and (vii) a C 1-6 alkyl-carbonyl group optionally substituted by a halogen atom or an amino group.

5. A Compound as claimed in claim 1 , wherein R 2 is an unsubstituted amino group.

6. A Compound as claimed in claim 1 , wherein B is an optionally-substituted benzene ring.

7. A Compound as claimed in claim 1 , wherein X is an oxygen atom.

8. A Compound as claimed in claim 1 , wherein R 1 is an acyl group.

9. A Compound of the following formula, or a salt thereof

wherein Ring A is an optionally-substituted benzene ring;

Ring B is a benzene or cyclohexane ring optionally substituted by a C 1-6 alkoxy group;

Z is a C 6-14 aryl, C 3-10 cycloalkyl, piperidyl, thienyl, furyl, pyridyl, thiazolyl, indanyl or indolyl group optionally having from 1 to 3 substituents selected from a halogen atom, a formyl group, a halogeno-C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkyl-carbonyl group, an oxo group and a pyrrolidinyl group;

D is a C 1-6 alkylene group;

G is a C 1-6 alkylene group optionally having a phenylene group and optionally substituted by a phenyl group;

R 1 is (a) a hydrogen atom, (b) a C 1-6 alkyl, C 2-6 alkenyl, C 6-14 aryl or C 7-14 aralkyl group optionally substituted by substituent(s) selected from

(1) a halogen atom,

(2) a nitro group,

(3) an amino group optionally substituted by one or two substituents selected from a C 1-6 alkyl-carbonyl group, a C 6-14 aryl-carbonyl group, a C 1-6 alkyl group, a C 1-6 alkyloxy-carbonyl group, a C 7-14 aralkyloxy-carbonyl group, a C 1-6 alkyl-sulfonyl group and a C 6-14 aryl-sulfonyl group,

(4) (i) a C 1-6 alkyl group optionally substituted by a hydroxy group, a C 1-6 alkyl-carbonyl group, a C 6-14 aryl-carbonyl group, a carboxyl group or a C 1-6 alkoxy-carbonyl group, (ii) a phenyl group optionally substituted by a hydroxy group, (iii) a benzoyl group, or (iv) a hydroxy group optionally substituted by a mono- or di-C 1-6 alkylamino-carbonyl group,

(5) a C 3-6 cycloalkyl group,

(6) a phenyl group optionally substituted by a hydroxy group or a halogeno-C 1-6 alkyl group, and

(7) a thienyl group, a furyl group, a thiazolyl group, an indanyl group, an indolyl or a benzyloxycarbonylpiperidyl group, or (c) an acyl group;

R 2 is (1) an unsubstituted amino group, or (2) an amino group optionally having one or two substituents selected from

(i) a benzyl group,

(ii) a C 1-6 alkyl group optionally substituted by an amino or phenyl group,

(iii) a mono- or di-C 1-6 alkyl-carbamoyl or -thiocarbamoyl group,

(iv) a C 1-6 alkoxy-carbonyl group,

(v) a C 1-6 alkyl-sulfonyl group,

(vi) a piperidylcarbonyl group, and

(vii) a C 1-6 alkyl-carbonyl group optionally substituted by a halogen atom or an amino group;

X represents an oxygen atom or an optionally-oxidized sulfur atom; and

Y represents two hydrogen atoms;

E is —CON(R a )—

wherein R a is a hydrogen atom or a C 1-6 alkyl group; and

L is a C 1-6 alkylene group optionally substituted by a C 1-6 alkyl group.

10. A Compound as claimed in claim 1 , wherein Z is a phenyl group optionally substituted by a halogen atom; D is a C 1-6 alkylene group; G is a C 1-6 alkylene group; R 1 is (a) a C 1-6 alkyl or C 7-14 aralkyl group optionally substituted by substituent(s) selected from (1) a hydroxy group, (2) a phenyl group, (3) a thienyl, furyl, thiazolyl, indanyl, indolyl or benzyloxycarbonylpiperidyl group, and (4) an amino group optionally substituted by a C 1-6 alkyl-carbonyl, C 6-14 aryl-carbonyl, C 1-6 alkyl-sulfonyl or C 6-14 aryl-sulfonyl group, or (b) an acyl group; R 2 is an unsubstituted amino group; L is a C 1-6 alkylene group.

11. A method for producing a compound according to claim 1 , or a salt thereof, which comprises reacting a compound of a formula (IIa):

wherein R 2a represents an optionally-protected, optionally-substituted amino group; and the other symbols A, B, X, Y, L, R 1 and D have the same meanings as in claim 1 , or its salt with a compound of a formula (III):

wherein the symbols G, Z and R a have the same meanings as in claim 1 , or its salt to give a compound of a formula (Ia-a):

wherein the symbols A, B, X, Y, L, D, G, Z, R 1 , R 2a and R a have the same meanings as, in claim 1 , or its salt, optionally followed by de-protecting it.

12. A pharmaceutical composition comprising:

a compound of the following formula, or a salt thereof:

wherein Ring A represents an optionally-substituted benzene ring;

Ring B represents an optionally-substituted benzene or cycloalkane ring;

Z represents an optionally-substituted; cyclic hydrocarbon group or an optionally substituted heterocyclic group;

R 1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, or an acyl group;

R 2 represents an optionally-substituted amino group;

D is an optionally substituted C 1-6 alkylene group;

E represents —CON(R a )—

wherein R a represents a hydrogen atom or an optionally-substituted C 1-6 alkyl group;

G represents an optionally substituted C 1-6 alkylene group;

L represents an alkylene group optionally having from 1 to 5 substituents selected from;

(i) a C 1-6 alkyl group,

(ii) a halogeno-C 1-6 alkyl group,

(iii) a phenyl group,

(iv) a benzyl group,

(v) an optionally-substituted amino group,

(vi) an optionally-substituted hydroxy group, and

(vii) a carbamoyl or thiocarbamoyl group optionally substituted by:

<1> a C 1-6 alkyl group,

<2> an optionally-substituted phenyl group, or

<3> an optionally-substituted heterocyclic group;

X represents an oxygen atom or an optionally-oxidized sulfur atom; and

Y represents two hydrogen atoms;

and a pharmaceutically acceptable carrier.

13. A method for treating diabetes comprising administering a pharmaceutically effective amount of a compound of the following formula or a salt thereof

wherein Ring A represents an optionally-substituted benzene ring;

Ring B represents an optionally-substituted benzene or cycloalkane ring;

Z represents an optionally-substituted; cyclic hydrocarbon group or an optionally substituted heterocyclic group;

R 1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, or an acyl group;

R 2 represents an optionally-substituted amino group;

D is an optionally substituted C 1-6 alkylene group;

E represents —CON(R a )—

wherein R a represents a hydrogen atom or an optionally-substituted C 1-6 alkyl group;

G represents an optionally substituted C 1-6 alkylene group;

L represents an alkylene group optionally having from 1 to 5 substituents selected from;

(i) a C 1-6 alkyl group,

(ii) a halogeno-C 1-6 alkyl group,

(iii) a phenyl group,

(iv) a benzyl group,

(v) an optionally-substituted amino group,

(vi) an optionally-substituted hydroxy group, and

(vii) a carbamoyl or thiocarbamoyl group optionally substituted by:

<1> a C 1-6 alkyl group,

<2> an optionally-substituted phenyl group, or

<3> an optionally-substituted heterocyclic, group;

X represents an oxygen atom or an optionally-oxidized sulfur atom; and

Y represents two hydrogen atoms;

to a mammal in need thereof.

14. A method for treating obesity comprising administering a pharmaceutically effective amount of a compound of the following formula or a salt thereof

wherein Ring A represents an optionally-substituted benzene ring;

Ring B represents an optionally-substituted benzene or cycloalkane ring;

Z represents an optionally-substituted; cyclic hydrocarbon group or an optionally substituted heterocyclic group;

R 1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, or an acyl group;

R 2 represents an optionally-substituted amino group;

D is an optionally substituted C 1-6 alkylene group;

E represents —CON(R a )—

wherein R a represents a hydrogen atom or an optionally-substituted C 1-6 alkyl group;

G represents an optionally substituted C 1-6 alkylene group;

L represents an alkylene group optionally having from 1 to 5 substituents selected from;

(i) a C 1-6 alkyl group,

(ii) a halogeno-C 1-6 alkyl group,

(iii) a phenyl group,

(iv) a benzyl group,

(v) an optionally-substituted amino group,

(vi) an optionally-substituted hydroxy group, and

(vii) a carbamoyl or thiocarbamoyl group optionally substituted by:

<1> a C 1-6 alkyl group,

<2> an optionally-substituted phenyl group, or

<3> an optionally-substituted heterocyclic, group;

X represents an oxygen atom or an optionally-oxidized sulfur atom; and

Y represents two hydrogen atoms;

to a mammal in need thereof.

15. A compound of the following formula, or a salt thereof:

wherein Ring A represents a benzene ring substituted with halogen;

Ring B represents a benzene or cycloalkane ring;

Z represents a halogenated cyclic hydrocarbon group;

R 1 represents an acyl group substituted with an optionally substituted hydrocarbon group;

R 2 represents an optionally-substituted amino group;

D is methylene, ethylene, propylene or butylene;

E represents —CON(R a )—

wherein R a represents a hydrogen atom;

G is methylene or ethylene;

L is methylene or ethylene;

X represents an oxygen atom or a sulfur atom; and

Y represents two hydrogen atoms.

16. N-(2-fluorobenzyl)-4-[N′-[2-(3-aminomethylphenoxy)-4-chlorophenyl]-N′-(4-phenylbenzoyl)]aminobutylamide or a salt thereof.

17. A method for treating diabetes comprising administering a pharmaceutically effective amount of N-(2-fluorobenzyl)-4-[N′-[2-(3-aminomethylphenoxy)-4-chlorophenyl]-N′-(4-phenylbenzoyl)]aminobutylamide or a salt thereof to a mammal in need thereof.

18. A method for treating obesity comprising administering a pharmaceutically effective amount of N-(2-fluorobenzyl)-4-[N′-[2-(3-aminomethylphenoxy)-4-chlorophenyl]-N′-(4-phenylbenzoyl)]aminobutylamide or a salt thereof to a mammal in need thereof.