Treatment of sexual dysfunction

• US 20020169101A1
• Filed: 11/15/2001
• Published: 11/14/2002
• Est. Priority Date: 05/10/1999
• Status: Abandoned Application

• Current Assignee: Warner-Lambert Company (Pfizer Inc.)
• Original Assignee: Warner-Lambert Company (Pfizer Inc.)
• Inventors: Stock, Herman Thijs, Pinnock, Robert Denham, Naylor, Alisdair Mark, Higginbottom, Michael, Wayman, Christopher Peter, Van Der Graaf, Pieter Hadewijn, Pritchard, Martyn Clive, Gonzalez, Maria Isabel
• Application Number:
  US09/999,284
• Publication Number:
  US 20020169101A1
• Time in Patent Office: Days
• US Class Current: 514/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: G01N 2800/344 Disorders of the penis and the scrotum and erectile dysfuncrion

Abstract

Bombesin receptor antagonists have been found to be useful in the treatment of sexual dysfunction in both males and females. They may be selective BB1 antagonists or mixed BB1/BB2 antagonists. Combinations are disclosed of bombesin receptor antagonists with a range of other active compounds, for example PDE5 inhibitors, NEP inhibitors and lasofoxifene.

Claims

1. A method of treating sexual dysfunction which comprises administering to a subject suffering therefrom and in need of treatment an effective amount of a bombesin receptor antagonist.

2. The method of claim 1, wherein the subject is a human male.

3. The method of claim 2, wherein the subject is suffering from erectile dysfunction.

4. The method of claim 3, wherein the subject is suffering from erectile dysfunction that is psychogenic.

5. The method of claim 3, wherein the subject is suffering from erectile dysfunction that is hormonal or endocrinologic.

6. The method of claim 3, wherein the subject is suffering from erectile dysfunction that is neurogenic.

7. The method of claim 3, wherein the subject is suffering from erectile dysfunction that is drug-induced.

8. The method of claim 3, wherein the subject is suffering from erectile dysfunction that is arteriogenic and/or venogenic and/or related to cavernosal factors.

9. The method of claim 2, wherein the subject is suffering from hypoactive sexual desire.

10. The method of claim 2, wherein the subject is suffering from delayed orgasm disorder.

11. The method of claim 1, wherein the subject is a human female.

12. The method of claim 11, wherein the subject is suffering from sexual arousal disorder.

13. The method of claim 12, wherein the subject is suffering from sexual arousal disorder that is arteriogenic and/or vasculogenic.

14. The method of claim 12, wherein the subject is suffering from sexual arousal disorder that is neurogenic.

15. The method of claim 12, wherein the subject is suffering from sexual arousal disorder that is hormonal or endocrine.

16. The method of claim 12, wherein the subject is suffering from sexual arousal disorder that is psychogenic.

17. The method of claim 12, wherein the subject is suffering from sexual arousal disorder that is drug-induced.

18. The method of claim 11, wherein the subject is suffering from hypoactive sexual desire disorder.

19. The method of claim 11, wherein the subject is suffering from orgasmic disorder or anorgasmia.

20. The method of claim 11, wherein the subject is suffering from sexual pain disorder.

21. The method of claim 1, wherein the dysfunction is associated with generalised unresponsiveness and/or ageing-related decline in sexual arousability.

22. The method of claim 1, wherein the bombesin receptor antagonist is a selective bombesin BB1 antagonist.

23. The method of claim 22, wherein the bombesin BB1 antagonist has a selectivity for BB₁ over the other bombesin receptor subtypes greater than 10.

24. The method of claim 22, wherein the bombesin BB1 antagonist has a selectivity for BBI over the other bombesin receptor subtypes greater than 30.

25. The method of claim 22, wherein the bombesin BB1 antagonist has a selectivity for BB1 over the other bombesin receptor subtypes greater than 100.

26. The method of claim 1, wherein the bombesin receptor antagonist is a mixed BB1/BB2 antagonist.

27. The method of claim 1, wherein the bombesin receptor antagonist has a Ki against BB1 of less than 1000 nM.

28. The method of claim 1, wherein the bombesin receptor antagonist has a Ki against BB1 of less than 500 nM.

29. The method of claim 1, wherein the bombesin receptor antagonist has a Ki against BB1 of less than 100 nM.

30. The method of claim 1, wherein the bombesin receptor antagonist has a Ki against BB1 of less than 50 nM.

31. The method of claim 1, wherein the bombesin receptor antagonist has a Ki against BB1 of less than 10 nM.

32. The method of claim 1, wherein there is administered to the subject an effective amount of a non-peptide bombesin receptor antagonist.

33. The method of claim 32, wherein the non-peptide bombesin receptor antagonist is a compound that is absorbable when administered orally.

34. The method of claim 1, wherein there is administered to the subject an effective amount of a bombesin receptor antagonist which is a peptide.

40. The combination of claim 39, wherein the bombesin receptor antagonist is a compound of the formula (I)

41. The combination of claim 39, wherein the bombesin receptor antagonist is a compoundof Formula (Ia)

42. The combination of claim 40, wherein the bombesin receptor antagonist is a compound of Formula I wherein

Ar is unsubstituted phenyl;

R¹ is cyclopentyl or tert-butyl;

R⁴ and R⁵ are hydrogen;

R⁷ is methyl;

R⁶ is hydrogen;

R³ is phenyl with two isopropyl substituents, unsubstituted phenyl, or

Ar¹ is indolyl.

43. The combination of claim 40, wherein the bombesin receptor antagonist is a compound of Formula I wherein

Ar is 2,6-diisopropyl-phenyl, 4-nitro-phenyl, and 4-cyano-phenyl;

R⁴, R⁵, and R⁶ are hydrogen;

R⁷ is methyl;

R² is hydrogen or cyclohexyl; and

R³ is hydroxyl, pyridyl,

44. The combination of claim 39, wherein the bombesin receptor antagonist is

(S)3-(1H-Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide (also referred to as Compound 1) or one of its pharmaceutically acceptable salts or is

(2S)-N-{[1-(4-aminophenyl) cyclohexyl]methyl}-3-(1H-indol-3-yl)-2-methyl-2-{[(4-nitroanilino) carbonyl]amino} propanamide (also knowm as Compound 3) or one of its pharmaceutically acceptable salts.

45. The combination of claim 39, wherein the bombesin receptor antagonist is a compound set out below or a pharmaceutically acceptable salt thereof:

(S) N-cyclohexylmethyl-2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

N-cyclohexylmethyl-2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-N-methyl-propionamide;

N-cyclohexylmethyl-2-[3-(2,6-diisopropyl-phenyl)-1-methyl-ureido]-3-(1H-indol-3-yl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-2-methyl-3-(1-oxy-pyridin-2-yl)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-2-methyl-3-pyridin-2-yl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

2-[3-(2-tert-butyl-phenyl)-ureido]-N-cyclohexylmethyl-3-(1H-indol-3-yl)-2-methyl-propionamide;

N-cyclohexylmethyl-2-[3-(2,6-dichloro-phenyl)ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

N-cyclohexylmethyl-2-[3-(2,6-dimethoxy-phenyl)ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

N-cyclohexylmethyl-2-[3-(2,6-dimethylamino-phenyl)-ureido]-3-(1Hindol-3-yl)-2-methyl-propionamide;

(S) N-cyclohexylmethyl-3-(1H-indol-3-yl)-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide;

N-cyclohexylmethyl-2-[3-(2,2-dimethyl-1-phenyl)propyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

[S-(R*, R*)] 3-(1H-indol-3-yl)-2-methyl-2-{3-[1-(4-nitro-phenyl)-ethyl]-ureido}-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

N-(2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-3-(1H-indol-3-yl)-2-methyl-2-[3-(1-phenyl-cyclopentylmethyl)ureido]-propionamide;

(S)-N-(2,6-diisopropyl-phenyl)-2-[3-(2,2-dimethyl-1-phenyl-propyl)-ureido]-3-(1H-indol-3-yl)-propionamide;

(R)-N-(2,6-diisopropyl-phenyl)-2-[3-(2,2-dimethyl-1-phenyl-propyl)-ureido]-3-(1H-indol-3-yl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-N-(2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-3-(1H-indol-3-yl)-2-methyl-propionamide;

N-cyclohexyl-2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

N-(2-cyclohexyl-ethyl)-2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(3-methyl-butyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(3-phenyl-propyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(1,2,3,4-tetrahydro-naphthalen-1-yl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(2-phenyl-cyclohexyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-N-indan-1-yl-3-(1H-indol-3-yl)-2-methyl-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-N-(1-hydroxy-cyclohexylmethyl)-3-(1H-indol-3-yl)-2-methyl-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-phenyl-propionamide;

N-(1-hydroxy-cyclohexylmethyl)-3-(1H-indol-3-yl)-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide;

2-[3-(4-cyano-phenyl)-ureido]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S) 3-(1H-indol-3-yl)-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S) 3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-[3-(4-trifluoromethyl-phenyl)-ureido]-propionamide;

(S) 4-(3-{2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-ureido)-benzoic acid ethyl ester;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-3-(1H-imidazol-4-yl)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-3-(2-trifluoromethyl-phenyl)-propionamide;

2-[3-(2,6-diisopropyl-phenyl)-ureido]-2-methyl-3-(2-nitro-phenyl)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S) 3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide; and

N-cyclohexylmethyl-2-[3-(2,6-diisopropyl-phenyl)-ureido]-2-methyl-3-pyridin-2-yl-propionamide.

46. The combination of claim 39, wherein the bombesin receptor antagonist is a compound of formula (II) or a pharmaceutically acceptable salt thereof:

47. The combination of claim 39, wherein the bombesin receptor antagonist is a compound of the formula (IIa), or a pharmaceutically acceptable salt thereof:

48. The combination of claim 39, wherein the bombesin receptor antagonist is a compound has the formula (IIb) or (IIc) or is a pharmaceutically acceptable salt thereof:

49. The combination of claim 39, wherein the bombesin receptor antagonist is

(S)-3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[4-(4-nitro-phenyl)-oxazol-2-ylamino]-propionamide (also referred to as Compound 2) or a pharmaceutically acceptable salt.

50. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a pharmaceutically acceptable salt thereof:

(S)-3-(1H-indol-3-yl)-N-(1-methoxymethyl-cyclohexylmethyl)-2-methyl-2-[4-(4-nitro-phenyl)-oxazol-2-ylamino]-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-[4-(4-nitro-phenyl)-oxazol-2-ylamino]-N-(2-oxo-2-phenyl-ethyl)-propionamide;

(S)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[4-(4-nitro-phenyl)-oxazol-2-ylamino]-3-phenyl-propionamide;

(S)-2-[4-(4-cyano-phenyl)-oxazol-2-ylamino]-3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-propionamide;

(S)-3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-(4-phenyl-oxazol-2-ylamino)-propionamide;

(S)-2-(4-ethyl-oxazol-2-ylamino)-3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-propionamide;

(S)-3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[4-(4-nitro-phenyl)-thiazol-2-ylamino]-propionamide;

(S)-2-(benzooxazol-2-ylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(pyridin-4-ylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-(isoquinol-4-ylamino)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(pyrimidin-5-ylamino)-propionamide;

(S)-2-(biphenyl-2-ylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-m-tolylamino-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(6-phenyl-pyridin-2-ylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(R)-3-phenyl-2-phenylamino-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-phenylethylamino-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-[(benzofuran-2-ylmethyl)-amino]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide, and

(S)-3-(1H-indol-3-yl)-2-methyl-2-(4-nitro-benzylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide.

51. The combination of claim 39, wherein the bombesin receptor antagonist is a compound of formula (III) or a pharmaceutically acceptable salt thereof:

52. The combination of claim 51, wherein the bombesin receptor antagonist is a compound formula (III) in which:

k is 0 or 1;

l is 1;

m is 0 or 1;

n is 0 or 1;

X is —

C(O)—

, —

OC(O)—

, or —

SO₂—

;

Ar is benzofuryl, furyl, indolyl, isoquinolyl, naphthyl, phenyl, pyridyl, quinolyl or thienyl each unsubstituted or substituted with 1 or 2 substituents selected from alkoxy, cyano, halogen, nitro, phenyl, phenoxy, —

CF₃, —

(CH₂)_qNR⁷R⁸, wherein R⁷ and R⁸ can form a ring of between 5 to 7 atoms which may contain 1 or 2 oxygen or nitrogen atoms, or R⁷ and R⁸ can be independently selected from hydrogen, straight or branched alkyl of up to 4 carbon atoms or cyclic alkyl of 5 carbon atoms;

Ar¹ is independently selected from Ar, preferably indolyl, and can also be pyridyl-N-oxide;

R¹ and R⁶ can form a cyclic alkyl of from 5 to 7 carbon atoms or R¹ and R⁶ together are carbonyl;

R² is independently selected from unsubstituted or substituted pyridyl or is hydrogen, hydroxy, alkoxy, —

NMe₂, —

CONR¹²R¹³ wherein R¹² and R¹³ are each independently selected from H and CH₃;

R³, R⁴ and R⁵ are each independently selected from hydrogen and methyl.

53. The combination of claim 51, wherein the bombesin receptor antagonist is a compound of Formula (III) in which,

l is 1;

m is 1;

n is 0;

R² is 2-pyridyl;

R⁶ forms a cyclohexyl with R¹.

54. The combination of claim 39, wherein the bombesin receptor antagonist is a compound of formula (IIIa) or a salt thereof:

55. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a salt thereof:

N-{(S)-2-(1H-indol-3-yl)-1-methyl-I -[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-4-nitro-benzamide;

C-dimethylamino-N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

1H-indole-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

benzo[b]thiophene-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

N-{(S)-2-(1H-Indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbarnoyl]-ethyl}-2-pyrrol-1-yl-benzamide

1H-indole-5-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide; and

1H-indole-2-carboxylic acid ((S)-2-(1H-indol-3-yl)-1-{[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-carbamoyl}-1-methyl-ethyl)-amide.

56. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a salt thereof

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-4-methyl-benzamide;

4-chloro-N-{(S)-2-(iH-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-4-methoxy-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-4-methanesulfonyl-benzamide;

3-cyano-N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

3-chloro-N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-3-methoxy-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-3-methanesulfonyl-benzamide;

dimethylamino-N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-3-methyl-benzamide;

2-chloro-N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-2-nitro-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-2-methoxy-benzamide;

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-2-methyl-benzamide;

2-fluoro-N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-benzamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2-p-tolyl-ethanoylamino)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2-o-tolyl-ethanoylamino)-propionamide;

(S)-2-[2-(4-hydroxy-phenyl)-ethanoylamino]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-[2-(3-hydroxy-phenyl)-ethanoylamino]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2-m-tolyl-ethanoylamino)-propionamide;

(S)-2-[2-(2-fluoro-phenyl)-ethanoylamino]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2-thiophen-3-yl-ethanoylamino)-propionamide;

pyridine-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-isonicotinamide;

furan-3-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

furan-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl- cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

5-methyl-isoxazole-3-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1-methyl-1H-pyrrole-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

thiophene-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

thiophene-3-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-l -[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1H-indole-6-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1H-indole-5-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1H-indole-4-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1H-indole-7-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1-methyl-1H-indole-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

benzothiazole-6-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

1H-benzotriazole-5-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

3-methyl-thiophene-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

5-methyl-thiophene-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

6-methyl-pyridine-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

isoquinoline-3-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

quinoxaline-2-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

quinoline-8-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

5-phenyl-oxazole-4-carboxylic acid {(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-amide;

(S)-3-(1H-indol-3-yl)-2-[2-(4-methoxy-phenyl)-ethanoylamino]-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-[2-(4-dimethylamino-phenyl)-ethanoylamino]-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-[2-(2-nitro-phenyl)-ethanoylamino]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-[2-(2-methoxy-phenyl)-ethanoylamino]-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide; and

N-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-2-pyrrol-1-yl-benzamide.

57. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a salt thereof

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid naphthalen-1-ylmethyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3,4-dichloro-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbarnic acid 3-nitro-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3-trifluoromethyl-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid quinolin-6-ylmethyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 4-nitro-benzyl ester; and

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3-cyano-benzyl ester.

58. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a salt thereof:

{(S)-2-(1H-indol-3-yl)-1-methyl-I -[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3,4-dimethoxy-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid naphthalen-2-ylmethyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid indan-2-yl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 4-methoxy-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 4-chloro-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 2-fluoro-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 2-chloro-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 2-methyl-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-I -[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 4-tert-butyl-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 2-methoxy-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 4-trifluoromethyl-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3-ethoxy-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 2,4-dichloro-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3-methyl-benzyl ester;

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 3-phenoxy-benzyl ester; and

{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethyl}-carbamic acid 4-methyl-benzyl ester.

59. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a salt thereof:

(S)-3-(1H-indol-3-yl)-2-methyl-2-phenylmethanesulfonylamino-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2-chloro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(naphthalene-1-sulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(quinoline-8-sulfonylamino)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2-trifluoromethyl-benzenesulfonylamino)-propionamide;

(S)-2-(biphenyl-2-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(5-methyl-2-phenoxy-benzenesulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide; and

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2-p-tolyloxy-benzenesulfonylamino)-propionamide.

60. The combination of claim 39, wherein the bombesin receptor antagonist is one of the following compounds or a salt thereof:

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(toluene-4-sulfonylamino)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methanesulfonylamino-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2-fluoro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(4-chloro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2,2,2-trifluoro-ethanesulfonylamino)-propionamide;

(S)-2-(5-dimethylamino-naphthalene-1-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(naphthalene-2-sulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(l -pyridin-2-yl-cyclohexylmethyl)-2-(thiophene-2-sulfonylamino)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(3-nitro-benzenesulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(4-fluoro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(4-nitro-benzenesulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(3-trifluoromethyl-benzenesulfonylamino)-propionamide;

(S)-2-(3,4-dichloro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(3-fluoro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(4-trifluoromethyl-benzenesulfonylamino)-propionamide;

(S)-2-(5-chloro-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(3-chloro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(toluene-3-sulfonylamino)-propionamide;

(S)-2-(3 ,4-dimethoxy-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(4-cyano-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2-cyano-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(3,5-dimethyl-isoxazole-4-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(benzo [1,2,5]thiadiazole-4-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(1-methyl-1H-imidazole-4-sulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(benzo[1,2,5]oxadiazole-4-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

3-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethylsulfamoyl}-thiophene-2-carboxylic acid methyl ester;

(S)-3-(1H-indol-3-yl)-2-(5-isoxazol-3-yl-thiophene-2-sulfonylamino)-2-methyl-N-(l -pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(2-nitro-phenylmethanesulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(3-cyano-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(1,2-dimethyl-1H-imidazole-4-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-(3-methoxy-benzenesulfonylamino)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(8-nitro-naphthalene-1-sulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2-chloro-5-nitro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(2,4,6-trichloro-benzenesulfonylamino)-propionamide;

(S)-2-(4-chloro-2-nitro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(5-benzenesulfonyl-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(4-trifluoromethoxy-benzenesulfonylamino)-propionamide;

2-{(S)-2-(1H-indol-3-yl)-1-methyl-1-[(1-pyridin-2-yl-cyclohexylmethyl)-carbamoyl]-ethylsulfamoyl}-benzoic acid methyl ester;

(S)-2-(3-chloro-4-fluoro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2,5-dichloro-thiophene-3-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(3-chloro-4-methyl-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-(2-methoxy-4-methyl-benzenesulfonylamino)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-2-(5-pyridin-2-yl-thiophene-2-sulfonylamino)-propionamide;

(S)-2-(5-bromo-6-chloro-pyridine-3-sulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2,4-dinitro-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-(4-methanesulfonyl-benzenesulfonylamino)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(4-tert-butyl-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2,4-dichloro-5-methyl-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-2-(2-chloro-5-trifluoromethyl-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide;

(S)-3-(1H-indol-3-yl)-2-methyl-2-(2-nitro-4-trifluoromethyl-benzenesulfonylamino)-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide; and

(S)-2-(4-butyl-benzenesulfonylamino)-3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide.

61. The combination of claim 39, which is in the form of a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.

62. The combination of claim 39, adapted for oral administration.

63. Use of a combination as claimed in claim 39 in the preparation of a medicament for the treatment or prophylaxis of male sexual dysfunction (more particularly male erectile dysfunction) and/or female sexual dysfunction (more particularly hypoactive sexual desire disorders, sexual arousal disorders, anorgasmic disorders or sexual pain disorders.

35. A method of treating sexual dysfunction in a male or female subject suffering therefrom and in need of treatment which comprises administering to the subject an effective amount of a bombesin receptor antagonist and a PDE 5 inhibitor.

36. A method of treating sexual dysfunction in a male or female subject suffering therefrom and in need of treatment which comprises administering to the subject an effective amount of a bombesin receptor antagonist and a NEP inhibitor.

37. A method of treating sexual dysfunction in a female subject suffering therefrom and in need of treatment which comprises administering to the subject an effective amount of a bombesin receptor antagonist and one or more estrogen receptor modulators (SERM) and/or estrogen agonists and/or estrogen antagonists.

38. A method of treating sexual dysfunction in a male or female subject suffering therefrom and in need of treatment which comprises administering to the subject an effective amount of a bombesin receptor antagonist and lasofoxifene.

39. A pharmaceutical combination (for simultaneous, separate or sequential administration) of a bombesin receptor antagonist and one or more materials selected from (1) to (34) below:

(1) naturally occurring or synthetic prostaglandins or esters thereof;

(2) α

-adrenergic receptor antagonist compounds also known as α

-adrenoceptor antaginists or α

-receptor antagonists or α

-blockers;

(3) NO-donor (NO-agonist) compounds;

(4) potassium channel openers or modulators;

(5) dopaminergic agents;

(6) vasodilator agents;

(7) thromboxane A2 agonists;

(8) CNS active agents;

(9) ergot alkaloids;

(10) compounds which modulate the action of natriuretic factors;

(11) angiotensin receptor antagonists such as losartan.;

(12) substrates for NO-synthase;

(13) calcium channel blockers;

(14) cholesterol lowering agents;

(15) antiplatelet and antithrombotic agents;

(16) insulin sensitising agents and hypoglycaemic agents;

.

(17) L-DOPA or carbidopa;

(18) acetylcholinesterase inhibitors;

(19) steroidal or non-steroidal anti-inflammatory agents;

(20) estrogen receptor modulators and/or estrogen agonists and/or estrogen antagonists, and pharmaceutically acceptable salts thereof;

(21) PDE inhibitors;

(22) NPY (neuropeptide Y) inhibitors;

(23) NEP inhibitors;

(24) vasoactive intestinal proteins (VIP), VIP mimetics, VIP analogues, VIP receptor agonists or VIP analogues or VIP fragments, or α

-adrenoceptor antagonists with VIP combinations;

(25) melanocortin receptor agonists or modulators or melanocortin ehancers;

(26) serotonin receptor agonists, antagonists or modulators;

(27) testosterone replacement agents, testosternone, dihydrotestosterone or a testosterone implant;

(28) estrogen, estrogen and medroxyprogesterone or medroxyprogesterone acetate (MPA) (i.e. as a combination), or estrogen and methyl testosterone hormone replacement therapy agents;

(29) modulators of transporters for noradrenaline, dopamine and/or serotonin;

(30) purinergic receptor agonists and/or modulators;

(31) neurokinin (NK) receptor antagonists;

(32) opioid receptor agonists, antagonista or modulators;

(33) agonists or modulators for oxytocin/vasopressin receptors; and

(34) modulators of cannabinoid receptors.

64. A pharmaceutical combination (for simultaneous, separate or sequential administration) of a bombesin receptor antagonist and a PDE 5 inhibitor.

65. A pharmaceutical combination (for simultaneous, separate or sequential administration) of a bombesin receptor antagonist and a NEP inhibitor.

66. A pharmaceutical combination (for simultaneous, separate or sequential administration) of a bombesin receptor antagonist and one or more estrogen receptor modulators (SERM) and/or estrogen agonists and/or estrogen antagonists.

67. A pharmaceutical combination (for simultaneous, separate or sequential administration) of a bombesin receptor antagonist and lasofoxifene.