Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1998-07-17
2001-12-11
Kight, John (Department: 1612)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S309000, C514S317000, C544S349000, C544S353000, C544S354000, C546S020000
Reexamination Certificate
active
06329390
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to 5-bicycloindole compounds, to pharmaceutical compositions containing them and to their medical use, particularly in the treatment of CNS conditions.
BACKGROUND OF THE INVENTION
Through its interaction with receptors borne on neuronal and other cells, 5-hydroxytryptamine (5-HT or serotonin) exerts various physiological effects. Imbalances in this interaction are believed to be responsible for such conditions as anxiety, hallucination, migraine, chemotherapy-induced nausea and for disorders in sexual activity, car diovascular activity and thermoregulation, among others. From an improved understanding of the 5-HT receptor population, it is apparent that these effects are mediated selectively through individual types and subtypes of the 5-HT receptors. Migraine, for example, has been treated with ergolamine, dihydroergotamine, methylsergide and, most recently, sumatriptan, all of which presumably act at 5-HT
1D
receptor subtype.
Current treatments for migraine, including sumatriptan, continue to have unwanted side effects. These include coronary vasospasm, hypertension and angina. Recent evidence suggests that sumatriptan's contraction of coronary arteries may be mediated by its stimulation of the 5-HT
1B
(formerly 5-HT
1D&bgr;
) subtype of the 5-HT receptors (Kaumann, A. J. Circulation, 1994, 90:1141-1153).
Given the physiological and clinical significance of the 5-HT
1D
receptor, and the potential side effect liability of stimulation of its 5-HT
1B
receptor, it would be desirable to provide compounds that bin I with high affinity to the 5-HT
1D
receptor. Such compounds would be medically useful for example to treat indications such as migraine and others for which administration of a 5-HT
1D
ligand is indicated. Also they could be used diagnostically, for example to identify these receptors and to screen drug candidates.
SUMMARY OF THE INVENTION
According to one aspect of the invention, there are provided compounds of Formula I and a salt, solvate or hydrate thereof:
wherein:
R
1
is selected from the group consisting of CR
5
R CH
2
NR
7
R
8
and a group of Formula II:
R
2
is selected from the group consisting of H, OH, C
1-6
alkyl and C
1-6
alkoxy; R
3
is selected from the group consisting of H, OH, C
1-6
alkyl, C
1-6
alkoxy,
C
1-6
alkylthio and optionally substituted benzyloxy;
n is selected from the group consisting of an integer of from 1-3;
Z is selected from the group consisting of C and N;
————— represents a single or double bond provided at only one double bond is present in the ring at a time;
R
4
is selected from the group consisting of H. OH, C
1-6
alkoxy or null, provided that when R
4
is selected from the group consisting of H, OH and C
1-6
alkoxy, Z is C and ————— represents a single bond and when R 4 is null, either Z is C and ————— represents a double bond or Z is N and ————— represents a single bond; one of R
5
and R
6
is independently selected from H, C
1-6
alkyl, C
1-6
alkoxy and hydroxy and the other of R
5
and R
6
is H;
R
7
and R
8
are independently selected from H and C
1-6
alkyl or R
7
and R
8
form an alkylene bridge which optionally incorporates heteroatom selected from O, NR
9
and S, and which, together with the nitrogen atom to which they are attached, creates an optionally substituted 3- to 7-membered carbo- or heterocyclic ring; and
R
9
is selected from the group consisting of H, C
1-6
alkyl and optionally substituted benzyl.
It is an aspect of the present invention to provide compounds that bind to the 5-HT
1D
receptor.
It is another aspect of the present invention to provide compounds which bind selectively to the 5-HT
1D
receptor, relative particularly to the 5-HT
1B
receptor.
In another aspect of the present invention there are provided compositions containing the present compounds either for use as reagents, for example in the identification of 5-HT
1D
receptor ligands or receptor ligands, or for pharmaceutical use to treat conditions where stimulation of the 5-HT
1D
receptor is indicated.
It is another aspect of the present invention to provide a method effective to treat medical conditions for which stimulation of the 5-HT
1D
receptor is indicated, such as to treat migraine.
These and other aspects of the present invention are described in greater detail hereinbelow.
REFERENCES:
International Publication No. WO 98/23587, International Publication Date Jun. 4, 1998.
Arora Jalaj
Slassi Abdelmalik
Tehim Ashok
Arent Fox Kintner & Plotkin & Kahn, PLLC
Covington Raymond
Kight John
NPS Allelix Corp.
LandOfFree
5-Bicycloindole compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 5-Bicycloindole compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 5-Bicycloindole compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2589640