Note: Claims are shown in the official language in which they were submitted.
-30-
CLAIMS:
1. Use of the active substance selected from
calcitonin gene-related peptide (CGRP) antagonists and CGRP
release inhibitors for treating menopausal hot flushes,
wherein the CGRP release inhibitors are selected from the
group of serotonin 5-HT1D-agonists selected from avitriptan,
eletriptan, naratriptan, rizatriptan, sumatriptan and
zolmitriptan.
2. Use according to claim 1, wherein the active
substance is a CGRP antagonist.
3. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-
lysyl]-4-(4-pyridinyl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
4. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(2,3,4,5-
tetrahydro-2(1H)-oxo-1,3-benzodiazepin-3-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
5. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxo-quinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
6. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
-31-
2(1H)-oxo-quinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
7. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-
2(2H)-oxo-imidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-
L-lysyl]-4-(4-pyridinyl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
8. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-
4-phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-L-lysyl]-4-(4-pyridinyl)-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
9. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxothieno[3,4-d]-pyrimidin-3-yl)-1-piperidinyl]carbonyl]-D-
tyrosyl]-4-(1-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
10. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(2,4-dihydro-5-
phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
11. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(2,4-dihydro-5-
-32-
phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
12. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(2,4-dihydro-5-
phenyl-3(3H)-oxo-1,2,4-triazol-2-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-
piperidinyl)-piperazine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
13. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxo-thieno[3,2-d]pyrimidin-3-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
14. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-l-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
15. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-hexyl-4-piperidinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
16. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
-33-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-cyclopropylmethyl-4-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
17. Use according to claim 2, wherein the CGRP
antagonist is 1-[N-[[4-[3,4-dihydro-2(1H)-oxoquinazolin-3-
yl]-1-piperidinyl]carbonyl]-3-ethenyl-D,L-phenylalanyl]-4-
(hexahydro-1H-1-azepinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
18. Use according to claim 2, wherein the CGRP
antagonist is (R,S)-1-[4-[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]-2-[(4-hydroxy-3,5-
dimethylphenyl)methyl]-1,4-dioxobutyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
19. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[N-
(aminocarbonyl)-N-phenyl-amino]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
20. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(5-methoxy-4-pyrimidinyl)-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
21. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,1-dioxido-
-34-
3(4H)-oxo-1,2,4-benzothiadiazin-2-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
22. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[2(1H)-
oxoquinolin-3-yl]-1-piperidinyl]carbonyl]-D-phenylalanyl]-4-
(1-piperidinyl)-piperidine, or a tautomer, a diastereomer,
an enantiomer, or a physiologically acceptable salt thereof.
23. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-[3-(dimethylamino)propyl]-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
24. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(4-methyl-1-piperazinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
25. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-[(1-methyl-4-piperidinyl)carbonyl]-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
26. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
-35-
phenylalanyl]-4-[(1-methyl-4-piperazinyl)carbonyl]-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
27. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-[4-[4-(dimethylamino)butyl]phenyl]-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
28. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-[4-(dimethylamino)-1-piperidinyl]-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
29. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-
oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-N'-methyl-D-
tryptyl]-4-(4-methyl-1-piperazinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
30. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[[4-(1,3-dihydro-4-phenyl-2(2H)-
oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-N'-(1,1-
dimethylethoxycarbonyl)-D-tryptyl]-4-(1-methyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
31. Use according to claim 2, wherein the CGRP
antagonist is (R,S)-1-[4-[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromo-4-
-36-
methylphenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-
piperazinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
32. Use according to claim 2, wherein the CGRP
antagonist is (R,S)-1-[4-[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,5-dibromo-4-
methoxyphenyl)methyl]-1,4-dioxobutyl]-4-(1-methyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
33. Use according to claim 2, wherein the CGRP
antagonist is (R,S)-1-[4-[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]-2-[(3,4-
dibromophenyl)methyl]-1,4-dioxobutyl]-4-(4-methyl-1-
piperazinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
34. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[N-[[4-(1,3-dihydro-2(2H) -
oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-3,5-dibromo-D-
tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
35. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-6-
hydroxy-2(2H)-oxobenzimidazol-1-yl)-1-piperidinyl]carbonyl]-
D-phenylalanyl]-4-(1-piperidinyl)-piperidine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
36. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-
2(2H)-oxo-benzimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
-37-
phenylalanyl]-N6,N6-dimethyl-L-lysyl]-4-(4-pyridinyl)-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
37. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxo-quinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-N6,N6-dimethyl-L-lysyl]-4-(4-pyridinyl)-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
38. Use according to claim 2, wherein the CGRP
antagonist is (R,S)-1-[2-(4-amino-3,5-dibromobenzoyl)-4-[4-
(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]-4-
oxobutyl]-4-(1-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
39. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-2,2-
dioxido-2,1,3-benzothiadiazin-3-yl)-1-piperidinyl]carbonyl]-
D-phenylalanyl]-4-(1-piperidinyl)-piperidine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
40. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-
2(2H)-oxoimidazo[4,5-c]quinolin-3-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-[(1-
piperidinyl)carbonyl]-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
41. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
-38-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
42. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-N6,N6-
dimethyl-L-lysyl]-4-(4-pyridinyl)-piperazine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
43. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-N-[[4-[4-(3-bromophenyl)-1,3-
dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-
dibromo-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
44. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(4-methyl-1-piperazinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
45. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
46. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
-39-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-
azabicyclo[3,2,1]oct-3-yl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
47. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-
2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-
4-(1-piperidinyl)-piperidine, or a tautomer, a diastereomer,
an enantiomer, or a physiologically acceptable salt thereof.
48. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-ethyl-4-
piperidinyl)-piperazine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
49. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(hexahydro-4-methyl-1H-1,4-diazepin-1-
yl)piperidine, or a tautomer, a diastereomer, an enantiomer,
or a physiologically acceptable salt thereof.
50. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-
(methylsulphonyl)-4-piperidinyl]-piperidine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
51. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
-40-
phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
52. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-
(trifluoromethyl)-phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-tyrosyl]-4-(hexahydro-1H-1-
azepinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
53. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-
methyl-4-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
54. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxo-quinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(exo-8-methyl-8-azabicyclo[3,2,1]oct-3-yl)-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
55. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
56. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-
-41-
(trifluoromethyl)-phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-tyrosyl]-4-(1-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
57. Use according to claim 2, wherein the CGRP
antagonist is 1-[N6-acetyl-N2-[3,5-dibromo-N-[[4-(3,4-
dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
58. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-
2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-
4-(hexahydro-1H-1-azepinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
59. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
(3-thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-
D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
60. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
61. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
-42-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-
(hydroxycarbonylmethyl)-4-piperidinyl]-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
62. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-methylsulphonyl-4-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
63. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
64. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
65. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
(3-hydroxyphenyl)-2(2H)-oxoimidazol-1-yl)-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
66. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-
-43-
(hexahydro-1H-1-azepinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
67. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
68. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[4-(3-
bromophenyl)-1,3-dihydro-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-
azabicyclo[3,2,1]oct-3-yl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
69. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
70. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-ethyl-4-piperidinyl)-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
71. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
-44-
(3-methoxyphenyl)-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(exo-8-methyl-8-
azabicyclo[3,2,1]oct-3-yl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
72. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-
oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-4-[1-
(cyclopropylmethyl)-4-piperidinyl]-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
73. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
74. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(3,4-dihydro-
2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(4-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
75. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-
2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-
4-(4-pyridinyl)-piperidine, or a tautomer, a diastereomer,
an enantiomer, or a physiologically acceptable salt thereof.
76. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-
-45-
(trifluoromethyl)-phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-tyrosyl]-4-(1-methyl-4-piperidinyl)-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
77. Use according to claim 2, wherein the CGRP
antagonist is 1-[N2-[3,5-dibromo-N-[[4-[1,3-dihydro-4-[3-
(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-
piperazine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
78. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(1,3-dihydro-4-(3-
thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
tyrosyl]-4-(1-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
79. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-N-[[4-[4-(3-chlorophenyl)-1,3-
dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-
dibromo-D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
80. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(hexahydro-1H-1-
azepinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
81. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
-46-
[3-(trifluoromethyl)phenyl]-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-
piperidinyl)-piperazine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
82. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-N-[[4-[4-(3-chlorophenyl)-1,3-
dihydro-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-3,5-
dibromo-D-phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-
piperidine, or a tautomer, a diastereomer, an enantiomer, or
a physiologically acceptable salt thereof.
83. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(4-pyridinyl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
84. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-(1,3-dihydro-4-phenyl-
2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-
4-(1-methyl-4-piperidinyl)-piperidine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
85. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-[4-(1-oxoethyl)phenyl]-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
86. Use according to claim 2, wherein the CGRP
antagonist is 1-[3,5-dibromo-N-[[4-[3,4-dihydro-2(1H)-
-47-
oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-4-(1-
methyl-4-piperidinyl)-piperazine, or a tautomer, a
diastereomer, an enantiomer, or a physiologically acceptable
salt thereof.
87. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[1,3-dihydro-4-
(3-nitrophenyl)-2(2H)-oxoimidazol-1-yl]-1-
piperidinyl]carbonyl]-D-phenylalanyl]-4-(1-methyl-4-
piperidinyl)-piperidine, or a tautomer, a diastereomer, an
enantiomer, or a physiologically acceptable salt thereof.
88. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-[3,4-dihydro-
2(1H)-oxoquinazolin-3-yl]-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(1-pyrrolidinyl)-piperidine, or a tautomer,
a diastereomer, an enantiomer, or a physiologically
acceptable salt thereof.
89. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
phenyl-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-D-
phenylalanyl]-4-(hexahydro-1H-1-azepinyl)-piperidine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
90. Use according to claim 2, wherein the CGRP
antagonist is 1-[4-amino-3,5-dibromo-N-[[4-(1,3-dihydro-4-
(3-thienyl)-2(2H)-oxoimidazol-1-yl)-1-piperidinyl]carbonyl]-
D-phenylalanyl]-4-(1-methyl-4-piperidinyl)-piperazine, or a
tautomer, a diastereomer, an enantiomer, or a
physiologically acceptable salt thereof.
91. Use of the active substance selected from CGRP
antagonists and CGRP release inhibitors in preparation of a
-48-
pharmaceutical composition for treating menopausal hot
flushes, wherein the CGRP release inhibitors are selected
from the group of serotonin 5-HT1D-agonists selected from,
avitriptan, eletriptan, naratriptan, rizatriptan,
sumatriptan and zolmitriptan.
92. Use according to claim 91, wherein the active
substance is a CGRP antagonist.
93. Use according to claim 92, wherein the CGRP
antagonist is one of the CGRP antagonists, tautomers,
diastereomers, enantiomers and salts defined in any one of
claims 3 to 90.
94. A pharmaceutical composition for treating
menopausal hot flushes, comprising the active substance
selected from CGRP antagonists and CGRP release inhibitors
and one or more inert carrier or diluent, wherein the CGRP
release inhibitors are selected from the group of serotonin
5-HT1D-agonists selected from avitriptan, eletriptan,
naratriptan, rizatriptan, sumatriptan and zolmitriptan.
95. A pharmaceutical composition according to claim
94, wherein the active substance is a CGRP antagonist.
96. A pharmaceutical composition for treating
menopausal hot flushes, comprising the active substance
selected from CGRP antagonists and CGRP release inhibitors
and one or more inert carrier or diluent, wherein the CGRP
release inhibitors are selected from the group of serotonin
5-HT1D-agonists selected from avitriptan, eletriptan,
naratriptan, rizatriptan, sumatriptan and zolmitriptan and
wherein the CGRP antagonist is one or more of the CGRP
antagonists, tautomers, diastereomers, enantiomers and salts
defined in any one of claims 3 to 90.
-49-
97. A commercial package comprising the active
substance selected from CGRP antagonists and CGRP release
inhibitors, together with printed matter comprising
instructions for use thereof for treating menopausal hot
flushes, wherein the CGRP release inhibitors are selected
from the group of serotonin 5-HT1D-agonists selected from
avitriptan, eletriptan, naratriptan, rizatriptan,
sumatriptan and zolmitriptan.
98. A commercial package according to claim 97,
wherein the active substance is a CGRP antagonist.
99. A commercial package comprising the active
substance selected from CGRP antagonists and CGRP release
inhibitors, together with printed matter comprising
instructions for use thereof for treating menopausal hot
flushes, wherein the CGRP release inhibitors are selected
from the group of serotonin 5-HT1D-agonists selected from
avitriptan, eletriptan, naratriptan, rizatriptan,
sumatriptan and zolmitriptan and wherein the CGRP antagonist
is the CGRP antagonist or the tautomer, diastereomer,
enantiomer or salt thereof defined in any one of claims 3
to 90.