Methods of treating neuropeptide Y-related conditions

Details Methods of treating neuropeptide Y-related conditions Methods of treating neuropeptide Y-related conditions

2001-06-29

2002-03-19

Henley, III, Raymond (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S414000

Reexamination Certificate

active

06358991

ABSTRACT:

This invention relates to methods of using substituted indole compounds in the treatment, prevention, inhibition or alleviation of conditions associated with an excess of neuropeptide Y.
BACKGROUND OF THE INVENTION
EP 0 802 183 A1 and U.S. Pat. No. 5,780,497 describe substituted indole compounds of the formulae below:
as well as their use as estrogenic agents, including the treatment of bone loss, cardiovascular disease, maladies associated with or resulting from the proliferation or abnormal development of endometrial or endometrial-like tissues, and disease states or syndromes associated with estrogen deficiency.
EP 0 802 184 A1, published Oct. 22, 1997, describes comparable uses for substituted indole compounds of the formulae below.
Analogous indole compounds having the general structures:
are described in U.S. Pat. No. 5,880,137 (Miller et al.).
U.S. Pat. No. 5,776,931 (Nunes et al.) describes the use of napthimidazolyl compounds in the treatment of conditions associated with an excess of neuropeptide Y. Similar methods of treatment utilizing raloxifene and its analogs are disclosed in U.S. Pat. No. 5,663,192 (Bruns, Jr. et al.). This use of raloxifene and its analogs is also described by Bruns, Jr. et al. for the treatment of obesity (U.S. Pat. No. 5,567,714), anxiety (U.S. Pat. No. 5,576,337), pain (U.S. Pat. No. 5,504,094), and depression (U.S. Pat. No. 5,567,715), each associated with an excess of neuropeptide Y. U.S. Pat. No. 5,972,888 (Bue-Valleskey et al.) teaches the use of a naturally occurring obesity protein in combination with a neuropeptide Y antagonist to treat these same maladies.
DESCRIPTION OF THE INVENTION
This invention comprises methods of therapeutic or prophylactic treatment of conditions associated with an excess of neuropeptide Y in a mammal, preferably in a human, the methods comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of the formulae I or II, below:
wherein Z is a moiety selected from the group of:
wherein:
R
1
is selected from H, OH or the C
1
-C
12
esters (straight chain or branched) or C
1
-C
12
(straight chain or branched or cyclic) alkyl ethers thereof, benzyloxy, or halogens; or C
1
-C
4
halogenated ethers including trifluoromethyl ether and trichloromethyl ether.
R
2
, R
3
, R
5
, and R
6
are independently selected from H, OH or the C
1
-C
12
esters (straight chain or branched) or C
1
-C
12
alkyl ethers (straight chain or branched or cyclic) thereof, halogens, or C
1
-C
4
halogenated ethers including trifluoromethyl ether and trichloromethyl ether, cyano, C
1
-C
6
alkyl (straight chain or branched), or trifluoromethyl, with the proviso that, when R
1
is H, R
2
is not OH;
R
4
is selected from H, OH or the C
1
-C
12
esters (straight chain or branched) or C
1
-C
12
alkyl ethers (straight chain or branched or cyclic) thereof, benzyloxy, halogens, or C
1
-C
4
halogenated ethers including trifluoromethyl ether and trichloromethyl ether, cyano, C
1
-C
6
alkyl (straight chain or branched), or trifluoromethyl;
X is selected from H, C
1
-C
6
alkyl, cyano, nitro, trifluoromethyl, halogen;
n is 1, 2 or 3;
Y is selected from:
a) the moiety:
 wherein R
7
and R
8
are independently selected from the group of H, C
1
-C
6
alkyl, or phenyl optionally substituted by CN, C
1
-C
6
alkyl (straight chain or branched), C
1
-C
6
alkoxy (straight chain or branched), halogen, —OH, —CF
3
, or —OCF
3
;
b) a five-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C
1
C
4
alkyl)-, —N═, and —S(O)
m
—, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C
1
-C
4
alkyl, trihalomethyl, C
1
-C
4
alkoxy, trihalomethoxy, C
1
-C
4
acyloxy, C
1
-C
4
alkylthio, C
1
-C
4
alkylsulfinyl, C
1
-C
4
alkylsulfonyl, hydroxy (C
1
-C
4
)alkyl, —CO
2
H—, —CN—, —CONHR
1
—, —NH
2
—, C
1
-C
4
alkylamino, di(C
1
-C
4
)alkylamino, —NHSO
2
R
1
—, —NHCOR
1
—, —NO
2
, and phenyl optionally substituted with 1-3 (C
1
-C
4
)alkyl;
c) a six-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C
1
C
4
alkyl)-, —N═, and —S(O)
m
—, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C
1
-C
4
alkyl, trihalomethyl, C
1
-C
4
alkoxy, trihalomethoxy, C
1
-C
4
acyloxy, C
1
-C
4
alkylthio, C
1
-C
4
alkylsulfinyl, C
1
-C
4
alkylsulfonyl, hydroxy (C
1
-C
4
)alkyl, —CO
2
H—, —CN—, —CONHR
1
—, —NH
2
—, C
1
-C
4
alkylamino, di(C
1
-C
4
)alkylamino, —NHSO
2
R
1
—, —NHCOR
1
—, —NO
2
, and phenyl optionally substituted with 1-3 (C
1
-C
4
)alkyl;
d) a seven-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C
1
C
4
alkyl)-, —N═, and —S(O)
m
—, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C
1
-C
4
alkyl, trihalomethyl, C
1
-C
4
alkoxy, trihalomethoxy, C
1
-C
4
acyloxy, C
1
-C
4
alkylthio, C
1
C
4
alkylsulfinyl, C
1
-C
4
alkylsulfonyl, hydroxy (C
1
-C
4
)alkyl, —CO
2
H—, —CN—, —CONHR
1
—, —NH
2
—, C
1
-C
4
alkylamino, di(C
1
-C
4
)alkylamino, —NHSO
2
R
1
—, —NHCOR
1
—, —NO
2
, and phenyl optionally substituted with 1-3 (C
1
-C
4
)alkyl; or
e) a bicyclic heterocycle containing from 6-12 carbon atoms either bridged or fused and containing up to two heteroatoms selected from the group consisting of —O—, —NH—, —N(C
1
C
4
alkyl)-, and —S(O)
m
—, wherein m is an integer of from 0-2, optionally substituted with 1-3 substituents independently selected from the group consisting of hydrogen, hydroxyl, halo, C
1
-C
4
alkyl, trihalomethyl, C
1
-C
4
alkoxy, trihalomethoxy, C
1
-C
4
acyloxy, C
1
-C
4
alkylthio, C
1
-C
4
alkylsulfinyl, C
1
-C
4
alkylsulfonyl, hydroxy (C
1
-C
4
)alkyl, —CO
2
H—, —CN—, —CONHR
1
—, —NH
2
—, C
1
-C
4
alkylamino, di(C
1
-C
4
)alkylamino, —NHSO
2
R
1
—, —NHCOR
1
—, —NO
2
, and phenyl optionally substituted with 1-3 (C
1
-C
4
) alkyl;
and the pharmaceutically acceptable salts thereof.
The more preferred compounds of this invention are those having the general structures I or II, above, wherein:
R
1
is selected from H, OH or the C
1
-C
12
esters or alkyl ethers thereof, benzyloxy, or halogen;
R
2
, R
3
, R
5
, and R
6
are independently selected from H, OH or the C
1
-C
12
esters or alkyl ethers thereof, halogen, cyano, C
1
-C
6
alkyl, or trihalomethyl, preferably trifluoromethyl, with the proviso that, when R
1
is H, R
2
is not OH;
R
4
is selected from H, OH or the C
1
-C
12
esters or alkyl ethers thereof, benzyloxy, halogen, cyano, C
1
-C
6
alkyl, or trihalomethyl;
X is selected from H, C
1
-C
6
alkyl, cyano, nitro, trifluoromethyl, halogen;
Y is the moiety
R
7
and R
8
are selected independently from H, C
1
-C
6
alkyl, or combined by —(CH
2
)p-, wherein p is an integer of from 2 to 6, so as to form a ring, the ring being optionally substituted by up to three substituents selected from the group of hydrogen, hydroxyl, halo, C
1
-C
4
alkyl, trihalomethyl, C
1
-C
4
alkoxy, trihalomethoxy, C
1
-C
4
alkylthio, C
1
-C
4
alkylsulfinyl, C
1
-C
4
alkylsulfonyl, hydroxy (C
1
-C
4
)alkyl, —CO
2
H, —CN, —CONH(C
1
-C
4
), —NH
3
, C
1
-C
4
alkylamino, C
1
-C
4
dialkylamino, —NHSO
2
(C
1
-C
4
), —NHCO(C
1
-C
4
), and —NO
3
;
and the pharmaceutically acceptable salts thereof.
The rings formed by a concatenated R
7
and R
8
, mentioned above, may include, but are not limited to, aziridine, azetidine, pyrrolidine, piperidine, hexamethyleneamine or heptamethyleneamine rings.
The most preferred compounds of the present invention are those having the structural formulas I or II, above, wherein R
1
is OH; R
2
-R
6
are as defined above; X is select

Affiliated with

Also associated with

Rating

Methods of treating neuropeptide Y-related conditions does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods of treating neuropeptide Y-related conditions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of treating neuropeptide Y-related conditions will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2853570