Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-12-10
2002-11-12
Rao, Deepak R. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S252140, C514S253010, C514S253060, C514S253110, C514S254050, C514S254070, C544S330000, C544S360000, C544S363000, C544S370000, C544S398000
Reexamination Certificate
active
06479495
ABSTRACT:
The present invention relates to aminoalkylphenols. More particularly, the present invention relates to aminoalkylphenol derivatives of formula 1
wherein:
R
1
is hydrogen, loweralkyl, a group of the formula CONR
6
R
7
, a group of the formula CH
2
COOR
8
, a group of the formula CH
2
CH
2
OH, a group of the formula CH
2
CN, or a group of the formula CH
2
C≈C—R
9
, a group of the formula
or a group of the formula Si(R
11
)
3
;
R
2
is hydrogen, loweralkyl, a group of the formula CONR
6
R
7
, a group of the formula SO
2
R
10
, a group of the formula
or a group of the formula Si(R
11
)
3
;
R
3
is hydrogen or loweralkyl;
R
4
is hydrogen or loweralkyl;
R
5
is hydrogen, loweralkyl, a group of the formula
or a group of the formula
R
4
and R
5
taken together with the nitrogen atom to which they are attached form a group of the formula
group of the formula
a group of the formula
a group of the formula
R
6
is hydrogen or loweralkyl;
R
7
is alkyl of 1 to 10 carbon atoms, or a group of the formula
a group of the formula
or a group of the formula
R
6
and R
7
taken together with the nitrogen atom to which they are attached form a group of the formula
R
8
is loweralkyl;
R
9
is hydrogen, a group of the formula C(R
14
R
14
)OH, a group of the formula
group of the formula
R
10
is loweralkyl;
R
11
is loweralkyl;
R
12
is loweralkyl, hydroxyloweralkyl, a group of the formula COR
15
, a group of the formula
a group of the formula
a group of the formula
a group of the formula
or a group of the formula
R
13
is hydrogen or loweralkyl;
R
14
is hydrogen or loweralkyl;
R
14
is hydrogen or loweralkyl;
R
15
is a group of the formula
or loweralkyl;
R
20
is loweralkyl;
X is hydrogen or halogen;
Z is hydrogen, halogen, loweralkyl, hydroxyl, loweralkoxy, trifluoromethyl, nitro or cyano, R
20
CO, or a group of the formula OCONR
6
R
7
;
m is 1 or 2;
n is 0 or 1;
p is 1 or 2;
q is 0, 1 or 2;
r is 0, 1 or 2;
the optical isomers thereof; or the pharmaceutically acceptable salts thereof, which are useful for relieving memory dysfunction and thus indicated in the treatment of Alzheimer's disease, alone, or in combination with adjuvants.
Subgeneric thereto are compounds wherein:
(a) R
1
is a group of the formula CONR
6
R
7
;
(b) R
2
is loweralkyl;
(c) R
2
is a group of the formula CONR
6
R
7
;
(d) R
1
is loweralkyl;
(e) R
4
and R
5
taken together with the nitrogen to which they are attached form a group of the formula
(f) R
1
is a group of the formula CONR
6
R
7
and R
4
and R
5
together with the nitrogen to which they are attached form a group of the formula
and n is 0; and
(g) R
2
is a group of the formula CONR
6
R
7
and R
4
and R
5
taken together with the nitrogen to which they are attached form a group of the formula
and n is 0.
The present invention also relates to compounds of formula 2
wherein R
16
and R
17
are independently hydrogen or alkyl of 1 to 10 carbon atoms and R
18
is a group of the formula
wherein W is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen or trifluoromethyl, and s is 1 or 2; X is hydrogen or halogen; m is 1 or 2, the optical isomers thereof; or the pharmaceutically acceptable salts thereof; of formula 3
wherein R
1
is loweralkyl, benzyl, or a group of the formula CH
2
C≈CH; or a group of the formula CONR
6
R
7
wherein R
6
is hydrogen and R
7
is loweralkyl; R
2
is hydrogen, loweralkyl, a group of the formula Si(R
11
), wherein R
11
is loweralkyl or R
2
is a group of the formula COR
6
R
7
wherein R
6
is hydrogen and R
7
is loweralkyl; X is hydrogen or halogen; m is 1 or 2; the optical isomers thereof; or salts thereof; of formula 4
wherein R
1
is loweralkyl, a group of the formula C≈CH, a group of the formula CH
2
COOR
8
, a group of the formula
a group of the formula CONR
6
R
7
or a group of the formula Si(R
11
)
3
; R
2
is a group of the formula SO
2
R
10
, a group of the formula
a group of the formula Si(R
11
)
3
or a group of the formula CONR
6
R
7
; R
8
is loweralkyl; Z is hydrogen, halogen, loweralkyl, hydroxyl, loweralkoxy, trifluoromethyl, nitro or cyano; p is 1 or 2; R
6
is hydrogen; R
7
is a group of the formula
wherein R
13
is loweralkyl and Z and p are as defined herein; and
R
11
is loweralkyl; X is hydrogen or halogen; m is 1 or 2, or the optical isomers thereof; and formula 5
wherein R
2
is hydrogen, loweralkyl or a group of the formula CONR
7
R
7
wherein R
6
and R
7
are loweralkyl; R
3
is hydrogen or loweralkyl; R
4
and R
5
taken together with the nitrogen atom to which they are attached form a group of the formula
wherein R
12
is a group of the formula
n is 0; X is hydrogen or halogen; m is 1 or 2 or the optical isomers thereof; or pharmaceutically acceptable salts thereof; which are useful as intermediates for the preparation of the aminoalkyl phenols of the present invention and for relieving memory dysfunction.
The invention also includes compounds of formula 43
wherein:
R
2
is hydrogen, loweralkyl or a group of the formula CONR
6
R
7
;
R
3
is hydrogen or loweralkyl;
R
4
and R
5
taken together with the nitrogen atom to which they are attached form a group of the formula
R
12
is a group of the formula
Z is hydrogen, halogen, loweralkyl, hydroxyl, loweralkoxy, trifluoromethyl, nitro, cyano or COCH
3
;
m is 1 or 2;
n is 0 or 1;
p is 1 or 2;
the optical isomers thereof, or the pharmaceutically acceptable salts thereof.
As used throughout the specification and appended claims, the term “alkyl” refers to a straight or branched chain hydrocarbon radical containing no unsaturation and having 1 to 12 carbon atoms. Examples of alkyl groups are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-pentyl, 3-hexyl, 4-heptyl, 2-octyl, 3-nonyl, 4-decyl, undecyl, dodecyl, and the like. The term “alkanol” refers to a compound formed by a combination of an alkyl group and hydroxy radical. Examples of alkanols are methanol, ethanol, 1- and 2-propanol, 2,2-dimethylethanol, hexanol, octanol, decanol and the like. The term “alkanoic acid” refers to a compound formed by combination of a carboxyl group with a hydrogen atom or alkyl group. Examples of alkanoic acids are formic acid, acetic acid, propanoic acid, 2,2-dimethylacetic acid, hexanoic acid, octanoic acid, decanoic acid and the like. The term “halogen” refers to a member of the family fluorine, chlorine, bromine, or iodine. The term “alkanoyl” refers to the radical formed by removal of the hydroxyl function from an alkanoic acid. Examples of alkanoyl groups are formyl, acetyl, propionyl, 2,2-dimethylacetyl, hexanoyl, octanoyl, decanoyl and the like. The term “alkoxy” refers to a monovalent substituent which consists of an alkyl group linked through an ether oxygen and having its free valence from the ether oxygen. Examples of alkoxy groups are methoxy, ethoxy, proproxy, 2,2-dimethylethoxy, hexoxy, octoxy, decoxy and the like. The term “lower” as applied to any of the aforementioned groups refers to a group having a carbon skeleton containing up to and including 10 carbon atoms.
The compounds of the present invention which lack an element of symmetry exist as optical antipodes and as the racemic forms thereof. The optical antipodes may be prepared from the corresponding racemic forms by standard optical resolution techniques, involving, for example, the separation of diastereomeric salts of those instant compounds characterized by the presence of a basic amino group and an optically active acid, those instant compounds characterized by the presence of a carboxyl acid group and an optically active base, or by synthesis from optically active precursors.
The present invention comprehends all optical isomers and racemic forms thereof of the compounds disclosed and claimed herein. The formulas of the compounds shown herein are intended to encompass all possible optical isomers of the compounds so depicted.
The novel aminoalkylphenols of the present invention are prepared by the processes illustrated in the Reaction Schemes. To prepare an ami
Kosley, Jr. Raymond W.
Palermo Mark G.
Shimshock Stephen J.
Wolf Veronica
Aventis Pharmaceuticals Inc.
Rao Deepak R.
Strupczewski Joseph
LandOfFree
Aminoalkylphenol derivatives and related 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 Aminoalkylphenol derivatives and related compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Aminoalkylphenol derivatives and related compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2956854