AMINOPIPERIDINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

• US 20070191364A1
• Filed: 01/25/2007
• Published: 08/16/2007
• Est. Priority Date: 07/29/2004
• Status: Abandoned Application

• Current Assignee: Sanofi-Aventis (Sanofi-Synthélabo SA)
• Original Assignee: Sanofi-Aventis (Sanofi-Synthélabo SA)
• Inventors: CRESPIN, Olivier, COURTEMANCHE, Gilles, PASCAL, Cecile, CORNET, Bruno, BRAUN, Alain, FETT, Eykmar
• Application Number:
  US11/626,972
• Publication Number:
  US 20070191364A1
• Time in Patent Office: Days
• US Class Current: 514/235.2
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 451/04 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
• CPC Class Codes: C07D 453/02 containing not further condensed quinuclidine ring systems

Abstract

The present invention relates to compounds of formula (I) as defined herein that are melanocortin receptor agonists, to the preparation thereof and to the therapeutic use thereof in the treatment and in the prevention of obesity, diabetes and sexual dysfunctions that can affect both sexes, in the treatment of cardiovascular diseases, and also in anti-inflammatory uses or in the treatment of alcohol dependency.

Claims

1. A compound corresponding to formula (I):

in which;

R_a and R_a′

, which may be identical to or different from one another, represent a hydrogen atom, or an alkyl or cycloalkyl group,

R₁ represents a hydrogen atom, or an alkyl cycloalkyl, heteroaryl or aryl group,

R₂ represents a group, of formula —

(CH₂)_n—

(CO)_y—

Y or —

(CO)_y—

(CH₂)_n—

Y, in which;

x=0, 1, 2, 3 or 4,

y=0 or 1,

Y represents a hydrogen atom, or a hydroxyl, alkyl, cycloalkyl, alkoxy, aryl, heteroaryl or —

NR₁₁R₁₂ group, Y being different from a hydrogen atom when x=y=0,

R₁₁ and R₁₂, which may be identical to or different from one another, represent a hydrogen atom, or an alkyl, cycloalkyl, alkoxy or —

NR₁₃R₁₄ group, or else R₁₁ and R₁₂ form, together with the nitrogen atom to which they are attached, a mono- or bicyclic structure containing from 4 to 10 ring members and optionally comprising 1 to 3 additional hetero atoms and/or 1 to 3 ethylenic or acetylenic unsaturations, this ring being optionally substituted in any positions with 1 to 3 groups chosen from halogen atoms, and hydroxyl, alkyl, cycloalkyl and alkoxy groups,

R₁₃ and R₁₄, which may be identical to or different from one another, represent a hydrogen atom, or an alkyl, cycloalkyl or alkoxy group, or else R₁₃ and R₁₄ form, together with the nitrogen atom to which they are attached, a mono- or bicyclic structure as defined above,

R₃ represents 1 to 3 groups, which may be identical to or different from one another, located in any positions of the ring to which they are attached and chosen from halogen atoms, and alkyl, cycloalkyl, —

OR, —

NRR′

, —

CO—

NRR′

, —

NR—

CO—

R′

, —

NR—

CO—

NRR′

, —

NR—

COOR′

, —

NO₂, —

CN and —

COOR groups,

R₅ represents a hydrogen atom or an alkyl or cycloalkyl group,

R₄ is chosen from the groups of formulae (a), (b) and (c), optionally substituted with an oxo group or mono- or polysubstituted with an aryl or heteroaryl group, below;

in which;

p=0, 1, 2 or 3,

m=0, 1 or 2,

and either

a) X represents a ring member —

N(R₁₀)—

, where

R₁₀ is chosen from;

a group —

(CH₂)_x—

OR₈, —

(CH₂)_x—

COOR₈, —

(CH₂)_x—

NR₈R₉, —

(CH₂)_x—

CO—

NR₈R₉ or —

(CH₂)_x—

NR₈—

COR₉, —

(CH₂)_x—

COR₈ in which x=1, 2, 3 or 4,

a cycloalkyl or heterocycloalkyl group fused with an aryl or heteroaryl group,

a cycloalkyl, heterocycloalkyl, aryl, hetero-aryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cyclo-alkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl, —

CO-alkylheteroaryl, —

CS-alkyl, —

CS-cycloalkyl, —

CS-heterocycloalkyl, —

CS-aryl, —

CS-heteroaryl, —

CS-alkylaryl, —

CS-alkylheteroaryl, —

CS—

NR₈R₉, —

C (═

NH)—

NR₈R₉, —

SO₂-alkyl, —

SO₂-cycloalkyl, —

SO₂-heterocycloalkyl, —

SO₂-aryl, —

SO₂-heteroaryl, —

SO₂-alkylaryl, —

SO₂-alkylheteroaryl or —

SO₂—

NR₈R₉ group,

the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups being optionally substituted with 1 or more groups chosen from the groups R, R′

, —

OR, —

NRR′

, —

CO—

NRR′

, —

NR—

CO—

R′

, —

NR—

CO—

NRR′

, —

NO₂, —

CN and —

COOR, OCOR, COR, OCONRR′

, NRCOOR′

the cycloalkyl or heterocycloalkyl groups being optionally fused with an aryl or heteroaryl group;

or else R₁₀ forms, with the nitrogen atom to which it is attached and a carbon atom located in any position of the cyclic structure of formula (a), but not adjacent to said nitrogen atom, a bridge comprising from 3 to 5 members,

R₈ and R₉ are chosen, independently of one another, from a hydrogen atom, and alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl, —

CO-alkylheteroaryl, —

SO₂-alkyl, —

SO₂-cycloalkyl, —

SO₂-heterocycloalkyl, —

SO₂-aryl, —

SO₂-heteroaryl, —

SO₂-alkylaryl, —

SO₂-alkylheteroaryl, —

C(═

NH)—

NRR′

, —

COOR, —

CO—

NRR′

, —

CS—

NRR′ and

—

(CH₂)_n—

OR groups, where x=0, 1, 2, 3 or 4,

or else R₈ and R₉ together form a cycloalkyl or a heterocycloalkyl;

R and R′

represent, independently of one another, a hydrogen atom, or an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl group, or can together form a cycloalkyl or a heterocycloalkyl;

or,

b) X represents a ring member —

C(R₆)(R₇)—

, where

R₆ is chosen from;

a hydrogen atom, a halogen atom,

a group —

(CH₂)_x—

OR₈, —

(CH₂)_x—

COOR₈, —

(CH₂)—

NR₈R₉, —

(CH₂)_x—

CO—

NR₈R₉ or —

(CH₂)_x—

NR₈—

COR₉, in which x=0, 1, 2, 3 or 4,

an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl or —

CO-alkylheteroaryl, —

CS-alkyl, —

CS-cycloalkyl, —

CS-heterocycloalkyl, —

CS-aryl, —

CS-heteroaryl, —

CS-alkylaryl, —

CS-alkylheteroaryl, —

CS—

NR₈R₉ or —

C(═

NH)—

NR₈R₉ group,

a fused or nonfused cycloalkyl or heterocycloalkyl group located in the spiro position on the ring of formula (a) to which it is attached,

a cycloalkyl or heterocycloalkyl group fused with an aryl or heteroaryl group,

the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups being optionally substituted with 1 or more groups chosen from the groups R, R′

, —

OR, —

NRR′

, —

CO—

NRR′

, —

NR—

CO—

R′

, —

NR—

CO—

NRR′

, —

NO₂, —

CN and —

COOR, OCOR, COR, OCONRR′

, NRCOOR′

;

the cycloalkyl or heterocycloalkyl groups being optionally fused with an aryl or heteroaryl group,

R₇ is chosen from hydrogen and halogen atoms, and alkyl, cycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

OR, —

O-aryl, —

O-heteroaryl, —

O-alkylaryl, —

O-alkylheteroaryl, —

NRR′

, —

CO—

NRR′

, —

NR—

CO—

R′

, —

NR—

CO—

NRR′

, —

NR—

COOR′

, —

NO₂, —

CN and —

COOR groups,

R₈ and R₉ are chosen, independently of one another, from a hydrogen atom, and alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl, —

CO-alkylheteroaryl, —

SO₂-alkyl, —

SO₂-cycloalkyl, —

SO₂-heterocycloalkyl, —

SO₂-aryl, —

SO₂-heteroaryl, —

SO₂-alkylaryl, —

SO₂-alkylheteroaryl, —

C (═

N—

H)—

NRR′

, —

COOR, —

CO—

NRR′

, —

CS—

NRR′ and

—

(CH₂)_n—

OR groups, where x=0, 1, 2, 3 or 4, the alkyl and aryl groups being optionally substituted with one or more groups chosen from the groups R, R′

, —

OR, —

NRR′

, —

CO—

NRR′

, —

NR—

CO—

R′

, —

NR—

CO—

NRR′

, —

NO₂, —

CN and —

COOR, OCOR, COR, OCONRR′

, NRCOOR′

;

or else R₈ and R₉ together form a cycloalkyl or a heterocycloalkyl;

R and R′

represent, independently of one another, a hydrogen atom, or an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl group, or can together form a cycloalkyl or a heterocycloalkyl,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

2. A compound according to claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c), optionally mono- or polysubstituted with an aryl or heteroaryl group, where X represents a ring member —

C(R₆) (R₇)—

, in which R₆ is chosen from;

a hydrogen atom,

a group —

(CH₂) x-OR₈, —

(CH₂) X—

COOR₈, —

(CH₂)_x—

NR₈R₉, —

(CH₂)_x—

CO—

NR₈R₉ or —

(CH₂)_x—

NR₈—

COR₉, in which x=0, 1, 2, 3 or 4,

an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl or —

CO-alkylheteroaryl group,

a cycloalkyl or heterocycloalkyl group located in the spiro position on the ring of formula (a) to which it is attached,

a cycloalkyl or heterocycloalkyl group fused with an aryl or heteroaryl group,

R₇ is chosen from hydrogen and halogen atoms, and alkyl, cycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

OR, —

O-aryl, —

O-heteroaryl, —

O-alkyl-aryl, —

O-alkylheteroaryl, —

NRR′

, —

CO—

NRR′

, —

NR—

CO—

R′

, —

NR—

CO—

NRR′

, —

NR—

COOR′

, —

NO₂, —

CN and —

COOR groups,

R₈ and R₉ are chosen, independently of one another, from a hydrogen atom, and alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl, —

CO-alkylheteroaryl, —

SO₂-alkyl, —

SO₂-cycloalkyl, —

SO₂-heterocycloalkyl, —

SO₂-aryl, —

SO₂-heteroaryl, —

SO₂-alkylaryl, —

SO₂-alkylheteroaryl, —

C(═

NH)—

NRR′

, —

COOR, —

CO—

NRR′

, —

CS—

NRR′ and

—

(CH₂)_n—

OR groups, where x=0, 1, 2, 3 or 4;

R and R′

represent, independently of one another, a hydrogen atom, or an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl group.

3. A compound according to claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

C(R₆)(R₇)—

, in which R₆ is chosen from a halogen atom, or a fused or nonfused cycloalkyl or heterocycloalkyl group located in the spiro position on the ring of formula (a) to which it is attached.

4. A compound according to claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

C(R₆)(R₇)—

, in which R₆ is chosen from —

CS-alkyl, —

CS-cycloalkyl, —

CS-heterocycloalkyl, —

CS-aryl, —

CS-heteroaryl, —

CS-alkylaryl, —

CS-alkylheteroaryl, —

CS—

NR₈R₉ and —

C(═

NH)—

NR₈R₉.

5. A compound to claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

C(R₆)(R₇)—

, in which the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups are optionally substituted with 1 or more groups chosen from R, R′

, OCOR, COR, OCONRR′ and

NRCOOR′

.

6. A compound according to claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

C(R₆)(R₇)—

, in which the cycloalkyl or heterocycloalkyl groups are optionally fused with an aryl or heteroaryl group.

7. A compound according to claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

C(R₆)(R₇)—

, in which R₈ and R₉, chosen independently of one another, represent alkyl and aryl groups which are optionally substituted with one or more groups chosen from the groups R, R′

, OCOR, COR, OCONRR′

or NRCOOR′

.

8. A compound of claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

C(R₆)(R₇)—

, in which R and R′

can together form a cycloalkyl or a heterocycloalkyl.

9. A compound of claim 1, wherein R₇ is hydrogen.

10. A compound of claim 1, wherein R₄ represents the group of formula a) where p=2 as defined below:

11. A compound of claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c), optionally mono- or polysubstituted with an aryl or heteroaryl group, where X represents a ring member —

N(R₁₀)—

in which

R₁₀ is chosen from;

a group —

CO—

NR₈R₉, —

COOR₈,

a group —

(CH₂)_x—

OR₈, —

(CH₂)_x—

COOR₈, —

(CH₂)—

NR₈R₉, —

(CH₂)—

CO—

NR₈R₉ or —

(CH₂)—

NR₈—

COR₉, in which x=1, 2, 3 or 4,

a cycloalkyl or heterocycloalkyl group fused with an aryl or heteroaryl group,

a cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-heteroaryl, —

CO-alkylaryl, —

CO-alkylheteroaryl, —

CS-alkyl, —

CS-cycloalkyl, —

CS-heterocycloalkyl, —

CS-aryl, —

CS-heteroaryl, —

CS-alkylaryl, —

CS-alkylheteroaryl, —

CS—

NR₈R₉, —

C(═

NH)—

NR₈R₉, —

SO₂-cycloalkyl, —

SO₂-heterocycloalkyl, —

SO₂-heteroaryl, —

SO₂-alkylaryl, —

SO₂-alkylheteroaryl or —

SO₂—

NR₈R₉ group;

or else R₁₀ forms, with the nitrogen atom to which it is attached and a carbon atom located in any position of the cyclic structure of formula (a), but not adjacent to said nitrogen atom, a bridge comprising from 3 to 5 members;

R₈ and R₉ are chosen, independently of one another, from a hydrogen atom, and alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, —

CO-alkyl, —

CO-cycloalkyl, —

CO-heterocycloalkyl, —

CO-aryl, —

CO-heteroaryl, —

CO-alkylaryl, —

CO-alkylheteroaryl, —

SO₂-alkyl, —

SO₂-cycloalkyl, —

SO₂-heterocycloalkyl, —

SO₂-aryl, —

SO₂-heteroaryl, —

SO₂-alkylaryl, —

SO₂-alkylheteroaryl, —

C(═

NH)—

NRR′

, —

COOR, —

CO—

NRR′

, —

CS—

NRR′ and

—

(CH₂)_n—

OR groups, where x=0, 1, 2, 3 or 4;

R and R′

represent, independently of one another, a hydrogen atom, or an alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl group.

12. A compound of claim 1, wherein

R₄ is chosen from the groups of formulae (a), (b) and (c) optionally substituted with an oxo group where X represents a ring member —

N(R₁₀).

13. A compound of claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

N(R₁₀)—

, in which

R₈ and R₉ together form a cycloalkyl or a heterocycloalkyl.

14. A compound of claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

N(R₁₀)—

, in which

R₁₀ is —

(CH₂)_x—

COR₈, in which x=1, 2, 3 or 4.

15. A compound of claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

N(R₁₀)—

, in which the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups are optionally substituted with one or more groups chosen from R, R′

OCOR, COR, OCONRR′

or NRCOOR′

.

16. A compound of claim 1, wherein R₄ is chosen from the groups of formulae (a), (b) and (c) where X represents a ring member —

N(R₁₀)—

, in which the cycloalkyl or heterocycloalkyl groups are optionally fused with an aryl or heteroaryl group.

17. A compound of claim 1, wherein R₄ represents the group of formula a) where p=2 as defined below:

18. A compound according to claim 1, wherein R₁ represents an alkyl, cycloalkyl or heterocycloalkyl group,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

19. A compound of claim 1, wherein R₂ is chosen from the following groups:

—

CO—

R₁₅, —

CO—

NR₁₆R₁₇, —

CO—

NR₁₅—

NR₁₆R₁₇, —

CO-aryl, —

CO-heteroaryl, —

CO—

(CH₂)_x—

NR₁₆R₁₇, —

(CH₂)_n—

NR₁₆R₁₇, —

(CH₂)_x—

OH, —

(CH₂)_x-aryl, —

(CH₂)_x-heteroaryl, —

(CH₂)_x—

CO—

R₁₅ and —

(CH₂)_n—

CO—

NR₁₆R₁₇, in which;

x=0, 1, 2, 3 or 4 and x′

=1, 2, 3 or 4,

R₁₅ represents a hydrogen atom, or an alkyl, cycloalkyl or alkoxy group, and

R₁₆ and R₁₇, which may be identical to or different from one another, represent a hydrogen atom, or an alkyl, cycloalkyl or alkoxy group, or else R₁₆ and R₁₇ form, together with the nitrogen atom to which they are attached, a mono- or bicyclic structure containing from 4 to 10 ring members and optionally comprising 1 to 3 additional hetero atoms and/or 1 to 3 ethylenic or acetylenic unsaturations, this ring being optionally substituted in any positions with 1 to 3 groups chosen from halogen atoms, and hydroxyl, alkyl, cycloalkyl and alkoxy groups,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

20. A compound of claim 1, wherein R₂ represents a group —

CO—

NR₁₆R₁₇, where R₁₆ and R₁₇ represent alkyl or alkoxy groups,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

21. A compound of claim 1, wherein R₃ represents 1 to 3 groups, which may be identical to or different from one another, chosen from halogen atoms,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

22. A compound of claim 1, wherein R₅ represents a hydrogen atom,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

23. A compound of claim 1, wherein R_a=R_a′

represent hydrogen atoms, or alkyl groups comprising from 1 to 4 carbon atoms,

in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate.

24. A compound of claim 1 selected from the group consisting of:

N-{1-[N-(4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-1,3-dihydro-2H-isoindole-2-carboxamide

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

-methoxy-N′

-methylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-2,5-dimethyl-2,5-dihydro-1H-pyrrole-1-carboxamide

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cycloheptyl-N′

,N′

-diethylurea

N-[1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclooctyl-N′

,N′

,-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

-(2,2,2-trifluoroethyl)urea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea (trans)

N-{1-[N-(trans-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}]-N-cyclohexyl-N′

,N′

-diethylurea (trans)

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

-ethyl-N′

-isopropylurea

N-(cis-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(diethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide

N-(trans-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(diethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide

N-{1-[N-(1-benzoylpiperidin-4-yl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea

N-{1-[N-(trans-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-bis(2-fluoroethyl)urea

(2R,5S)—

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl)-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

(2R,5S)-N-(1-{4-chloro-N-[cis-4-(dimethylamino)cyclohexyl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N,N-dimethylpiperidine-1-carboxamide

4-{([(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N,N-diethylpiperidine-1-carboxamide

N-(1-{4-chloro-N-[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]-D-phenylalanyl]piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(piperidin-1-ylcarbonyl)piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(morpholin-4-ylcarbonyl)piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N-phenylpiperidine-1-carboxamide

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-[(cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N-methyl-N-phenylpiperidine-1-carboxamide

N-benzyl-4-{([(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N-methylpiperidine-1-carboxamide

N-(1-{4-chloro-N-[1-(trifluoroacetyl)-piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-(1-acetylpiperidin-4-yl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[4-chloro-N-(cis-4-hydroxy-4-phenylcyclohexyl)-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[4-chloro-N-(trans-4-hydroxy-4-phenylcyclohexyl)-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-(cis-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide

N-(trans-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide

N-[1-(4-chloro-N-{cis-4-[(4-fluorophenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{trans-4-[(4-fluorophenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{cis-4-[(2-hydroxyphenyl)amino]cyclohexyl}-D-phenylalanyl)-piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{trans-4-[(2-hydroxyphenyl)amino]cyclohexyl}-D-phenylalanyl)-piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[4-chloro-N-(4-methoxycyclohexyl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-{1-[4-chloro-N-(4-phenylcyclohexyl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-{1-[N-(1-acetylpiperidin-4-yl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-(4-{[(1R)-1-(4-chlorobenzyl)-2-(4-(cyclohexyl[(dimethylamino)carbonyl]amino}-3-methylpiperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-acetamide (trans)

N-(1-{4-chloro-N-[1-(trifluoroacetyl)-piperidin-4-yl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-(4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}-3-methylpiperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide (trans)

N-{1-[1N-(1-benzoylpiperidin-4-yl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-(4-chloro-N-[1-(methylsulphonyl)-piperidin-4-yl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-1-[4-chloro-N-(4-hydroxy-4-phenylcyclohexyl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-[1-(4-chloro-N-{4-[(4-fluorophenyl)-amino]cyclohexyl}-D-phenylalanyl)-3-methylpiperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[1N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-[1-(4-chloro-N-{cis-4-[(2-methoxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{trans-4-[(2-methoxyphenyl)amino]cyclohexyl}-D-phenylalanyl)-piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-(cis-4-{[1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)acetamide

N-(trans-4-{[(R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)acetamide

N-(1-{4-chloro-N-[cis-4-(4-hydroxy-phenyl)cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[trans-4-(4-hydroxyphenyl)-cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[4-(2-oxo-1,3-oxazolidin-3-yl)cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-{[1-[4-chloro-N-(1-isonicotinoylpiperidin-4-yl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-(1-{4-chloro-N-[cis-4-(1,3-dihydro-2H-isoindol-2-yl)cyclohexyl]-D-phenylalanyl}-3-methyl-piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea (trans)

N-{1-[4-chloro-N-(2-phenylpiperidin-4-yl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea (trans) and

N-(1-{4-chloro-N-[4-(3-oxopiperazin-1-yl)cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea (trans).

25. A compound of claim 1 selected from the group consisting of:

N-{1-[N-(4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

,-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-1,3-dihydro-2H-isoindole-2-carboxamide

N-[1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

-methoxy-N′

-methylurea

N-[1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-2,5-dimethyl-2,5-dihydro-1H-pyrrole-1-carboxamide

N-[1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclobutyl-N′

,N′

-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclopentyl-N′

,N′

-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cycloheptyl-N′

,N′

-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclooctyl-N′

,N′

-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N′

,N′

-diethyl-N-phenylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

-(2,2,2-trifluoroethyl)urea

N-{1-[4-chloro-N-(4-hydroxycyclohexyl)-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea (trans)

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea (cis)

N-{1-[N-(trans-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea (trans)

N-{1-[N-(trans-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea (cis)

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N′

,N′

-diethyl-N-(tetrahydro-2H-pyran-4-yl)urea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N′

,N′

-diethyl-N-piperidin-4-ylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

-ethyl-N′

-isopropylurea

N-[1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-2,2-dimethylhydrazinecarboxamide

N-(cis-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(diethylamino)carbonyl]amino]piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide

N-(trans-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(diethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide and

N-[1-[N-(trans-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-bis (2-fluoroethyl)urea.

26. A compound of claim 1 selected from the group consisting of:

N-[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl-[2-(diethylamino)ethyl]amino}piperidin-1-yl)-2-oxoethyl]cyclohexane-1,4-diamine

N-(1-{4-chloro-N-[cis-4-(dimethylamino)-cyclohexyl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-3,4-difluorobenzamide

N-(1-{4-chloro-N-[cis-4-(dimethylamino)-cyclohexyl]-D-phenylalanyl}piperidin-4-yl)-N-cycloheptyl-N′

,N′

-dimethylurea

(2R,5S)—

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]piperidin-4-yl]-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

(2R,5S)—

N-(1-[4-chloro-N-[cis-4-(dimethylamino)cyclohexyl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

N-{1-[4-chloro-N-(cis-4-hydroxy-4-phenylcyclohexyl)-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[4-chloro-N-(trans-4-hydroxy-4-phenylcyclohexyl)-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-(cis-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoro-acetamide

N-(trans-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoro-acetamide

N-[1-(4-chloro-N-{cis-4-[(4-fluorophenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{trans-4-[(4-fluorophenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[4-chloro-N-(4-methoxycyclohexyl)-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{cis-4-[(4-methoxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{trans-4-[(4-methoxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{cis-4-[(2-hydroxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{trans-4-[(2-hydroxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-(4-[(dimethylamino)methyl]-4-phenylcyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

(2S,5S)—

N-(1-{4-chloro-N-[cis-4-(dimethylamino)cyclohexyl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

(2R,5R)—

N-(1-{4-chloro-N-[cis-4-(dimethylamino)cyclohexyl]-D-phenylalanyl]piperidin-4-yl)-N-cyclohexyl-2,5-dimethylpyrrolidine-1-carboxamide

N-{1-[4-chloro-N-(4-methoxycyclohexyl)-D-phenylalanyl]-3-methylpiperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-[4-chloro-N-(4-phenylcyclohexyl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-(4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}-3-methylpiperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-acetamide

N-(4-{[(1R)-1-(4-chlorobenzyl)-2-(4-[cyclohexyl[(dimethylamino)carbonyl]amino}-3-methylpiperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)-2,2,2-trifluoroacetamide

N-{1-[4-chloro-N-(4-hydroxy-4-phenylcyclohexyl)-D-phenylalanyl]-3-methylpiperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{4-[(4-fluorophenyl)amino]-cyclohexyl}-D-phenylalanyl)-3-methylpiperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[cis-4-(dimethylamino)-cyclohexyl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-(cis-4-aminocyclohexyl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-[cis-4-[(2-methoxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-[1-(4-chloro-N-{cis-4-[(2-methoxyphenyl)-amino]cyclohexyl}-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-dimethylurea

N-(cis-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-[cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)acetamide

N-(trans-4-{([(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}cyclohexyl)acetamide

N-(1-{4-chloro-N-[cis-4-(4-hydroxyphenyl)-cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[trans-4-(4-hydroxyphenyl)-cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[4-(2-oxo-1,3-oxazolidin-3-yl)cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-(4-chloro-N-[cis-4-(1,3-dihydro-2H-isoindol-2-yl)cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea and

N-(1-{4-chloro-N-[4-(3-oxopiperazin-1-yl)cyclohexyl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea.

27. A compound of claim 1 selected from the group consisting of:

N-[1-(N-8-azabicyclo[3.2.1]oct-3-yl-4-chloro-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-diethylurea

N-[1-(N-1-azabicyclo[2.2.2]oct-3-yl-4-chloro-D-phenylalanyl)piperidin-4-yl]-N-cyclohexyl-N′

,N′

-diethylurea

N-[1-(N-8-azabicyclo[3.2.1]oct-3-yl-4-chloro-D-phenylalanyl)piperidin-4-yl]-N-cyclobutyl-N′

,N′

-diethylurea and

N-{1-[N-(1-benzoylpiperidin-4-yl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-diethylurea.

28. A compound of claim 1 selected from the group consisting of:

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl-[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N,N-dimethylpiperidine-1-carboxamide

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-[cyclohexyl-[(dimethylamino)carbonyl]amino piperidin-1-yl)-2-oxoethyl]amino}-N,N-diethylpiperidine-1-carboxamide

N-(1-{4-chloro-N-[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(piperidin-1-ylcarbonyl)-piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(morpholin-4-ylcarbonyl)-piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl-[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N-phenylpiperidine-1-carboxamide

4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl-[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N-methyl-N-phenylpiperidine-1-carboxamide

N-benzyl-4-{[(1R)-1-(4-chlorobenzyl)-2-(4-{cyclohexyl[(dimethylamino)carbonyl]amino}piperidin-1-yl)-2-oxoethyl]amino}-N-methylpiperidine-1-carboxamide

N-(1-{4-chloro-N-[1-(trifluoroacetyl)-piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-(1-acetylpiperidin-4-yl)-4-chloro-D-phenylalanyl]piperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-(1-acetylpiperidin-4-yl)-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(trifluoroacetyl)-piperidin-4-yl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[N-[(1-benzoylpiperidin-4-yl}-4-chloro-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(methylsulphonyl)-piperidin-4-yl]-D-phenylalanyl}-3-methylpiperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-(1-{4-chloro-N-[1-(methylsulphonyl)-piperidin-4-yl]-D-phenylalanyl}piperidin-4-yl)-N-cyclohexyl-N′

,N′

-dimethylurea

N-{1-[4-chloro-N-(1-isonicotinoylpiperidin-4-yl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea and

N-{1-[4-chloro-N-(2-phenylpiperidin-4-yl)-D-phenylalanyl]-3-methylpiperidin-4-yl}-N-cyclohexyl-N′

,N′

-dimethylurea.

29. A medicament which comprises a compound of claim 1, or an addition salt of this compound with a pharmaceutically acceptable acid, or else a hydrate or a solvate of the compound of formula (I).

30. A pharmaceutical composition which comprises a compound of claim 1, or a pharmaceutically acceptable salt, a hydrate or a solvate of this compound, and also at least one pharmaceutically acceptable excipient.

31. A method of treatment or prevention of a condition selected from obesity, diabetes and sexual dysfunctions that can affect both sexes, in the treatment of cardiovascular diseases, and also in anti-inflammatory uses or in the treatment of alcohol dependency comprising administering to a patient in need thereof an effective amount of a compound of claim 1.

32. The method of claim 31, wherein said sexual dysfunctions consist of erectile dysfunctions.

33. A method for preparing a compound of claim 1, wherein a reductive amination of a compound of formula (V):

is carried out in the presence of a derivative of the group R₄ of ketone type, R₁, R₂, R₃, R₄, R₅, R_a and R_a′

, being as defined in claim 1.

34. A compound of formulae (VI), (XVIII) or (XIX), in which R₁, R₂, R₃, R₄, R₅, R_a and R_a′

are as defined in claim 1 and Pg represents a protective group;