Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-06-27
2004-02-17
Aulakh, Charanjit S. (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S082000
Reexamination Certificate
active
06693113
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to imidazonaphthyridine and tetrahydroimidazonaphthyridine compounds, processes for making these compounds and intermediates used in their preparation. This invention additionally relates to pharmaceutical compositions containing imidazonaphthyridine and tetrahydroimidazonaphthyridine compounds. A further aspect of this invention relates to the use of these compounds as immunomodulators and for inducing cytokine biosynthesis in animals.
BACKGROUND OF THE INVENTION
The first reliable report on the 1H-imidazo[4,5-c]quinoline ring system, Backman et al.,
J. Org. Chem.
15, 1278-1284 (1950) describes the synthesis of 1-(6-methoxy-8-quinolinyl)-2-methyl-1H-imidazo[4,5-c]quinoline for possible use as an antimalarial agent. Subsequently, syntheses of various substituted 1H-imidazo[4,5-c]quinolines were reported. For example, Jain et al.,
J. Med. Chem.
11, pp. 87-92 (1968), synthesized the compound 1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline as a possible anticonvulsant and cardiovascular agent. Also, Baranov et al.,
Chem. Abs.
85, 94362 (1976), have reported several 2-oxoimidazo[4,5-c]quinolines, and Berenyi et al.,
J. Heterocyclic Chem.
18, 1537-1540 (1981), have reported certain 2-oxoimidazo[4,5-c]quinolines.
Certain 1H-imidazo[4,5-c]quinolin-4-amines and 1- and 2-substituted derivatives thereof were later found to be useful as antiviral agents, bronchodilators and immunomodulators. These are described in, inter alia, U.S. Pat. Nos. 4,689,338; 4,698,348; 4,929,624; 5,037,986; 5,268,376; 5,346,905; and 5,389,640, all of which are incorporated herein by reference. Although there continues to be interest in the imidazoquinoline ring system, as seen for example in WO 98/30562, there is a continuing need for compounds that have the ability to modulate the immune response, by induction of cytokine biosynthesis or other mechanisms.
SUMMARY OF THE INVENTION
We have found a new class of compounds that are useful in inducing cytokine biosynthesis in animals. Accordingly, this invention provides imidazonaphthyridine compounds of Formula I:
wherein A, R
1
and R
2
are as defined hereinafter.
The invention also provides tetrahydroimidazonaphthyridine compounds of Formula II:
wherein B, R
1
and R
2
are as defined hereinafter.
The compounds of Formula I and Formula II are useful as immune response modifiers due to their ability to induce cytokine biosynthesis and otherwise modulate the immune reponse when administered to animals. This ability makes the compounds useful in the treatment of a variety of conditions, e.g. viral diseases and tumors that are responsive to such changes in the immune response.
The invention further provides pharmaceutical compositions containing a compound of Formula I or Formula II and methods of inducing cytokine biosynthesis in an animal and/or treating a viral infection in an animal by administering a compound of Formula I or Formula II to the animal.
In addition, methods of synthesizing compounds of Formula I and Formula II, and intermediates useful in the synthesis of these compounds are provided.
Further the invention provides a method of inducing interferon biosynthesis in an animal comprising the step of administering to said animal a compound of Formula I or Formula II in an amount effective to induce said interferon biosynthesis, and a method of treating a viral infection in an animal comprising the step of administering to said animal a compound of Formula I or Formula II in an amount effective to inhibit the viral infection.
DETAILED DESCRIPTION OF THE INVENTION
As mentioned earlier, the invention provides compounds of Formula I:
wherein
A is ═N—CR═CR—CR═; ═CR—N═CR—CR═; ═CR—CR═N—CR═; or ═CR—CR═CR—N═;
R
1
is selected from the group consisting of:
hydrogen;
—C
1-20
alkyl or C
2-20
alkenyl that is unsubstituted or substituted by one or more substituents selected from the group consisting of:
-aryl;
-heteroaryl;
-heterocyclyl;
—O—C
1-20
alkyl,
—O—(C
1-20
alkyl)
0-1
-aryl;
—O—(C
1-20
alkyl)
0-1
-heteroaryl;
—O—(C
1-20
alkyl)
0-1
-heterocyclyl;
—C
1-20
alkoxycarbonyl;
—S(O)
0-2
—C
1-20
alkyl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-aryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heteroaryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heterocyclyl;
—N(R
3
)
2
;
—N
3
;
oxo;
-halogen;
—NO
2
;
—OH; and
—SH; and
—C
1-20
alkyl-NR
3
—Q—X—R
4
or —C
2-20
alkenyl-NR
3
—Q—X—R
4
wherein Q is —CO— or —SO
2
—; X is a bond, —O— or —NR
3
— and R
4
is aryl; heteroaryl; heterocyclyl; or —C
1-20
alkyl or C
2-20
alkenyl that is unsubstituted or substituted by one or more substituents selected from the group consisting of:
-aryl;
-heteroaryl;
-heterocyclyl;
—O—C
1-20
alkyl,
—O—(C
1-20
alkyl)
0-1
-aryl;
—O—(C
1-20
alkyl)
0-1
-heteroaryl;
—O—(C
1-20
alkyl)
0-1
-heterocyclyl;
—C
1-20
alkoxycarbonyl;
—S(O)
0-2
—C
1-20
alkyl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-aryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heteroaryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heterocyclyl;
—N(R
3
)
2
;
—NR
3
—CO—O—C
1-20
alkyl;
—N
3
;
oxo;
-halogen;
—NO
2
;
—OH; and
—SH; or R
4
is
wherein Y is —N— or —CR—;
R
2
is selected from the group consisting of:
-hydrogen;
—C
1-10
alkyl;
—C
2-10
alkenyl;
-aryl;
—C
1-10
alkyl-O—C
1-10
-alkyl;
—C
1-10
alkyl-O—C
2-10
alkenyl; and
—C
1-10
alkyl or C
2-10
alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
—N(R
3
)
2
;
—CO—N(R
3
)
2
;
—CO—C
1-10
alkyl;
—N
3
;
-aryl;
-heteroaryl;
-heterocyclyl;
—CO-aryl; and
—CO-heteroaryl;
each R
3
is independently selected from the group consisting of hydrogen and C
1-10
alkyl; and
each R is independently selected from the group consisting of hydrogen, C
1-10
alkyl, C
1-10
alkoxy, halogen and trifluoromethyl, or a pharmaceutically acceptable salt thereof.
This invention also provides compounds of Formula II
wherein
B is —NR—C(R)
2
—C(R)
2
—C(R)
2
—; —C(R)
2
—NR—C(R)
2
—C(R)
2
—; —C(R)
2
—C(R)
2
—NR—C(R)
2
— or —C(R)
2
—C(R)
2
—C(R)
2
—NR—;
R
1
is selected from the group consisting of:
-hydrogen;
—C
1-20
alkyl or C
2-20
alkenyl that is unsubstituted or substituted by one or more substituents selected from the group consisting of:
-aryl;
-heteroaryl;
-heterocyclyl;
—O—C
1-20
alkyl;
—O—(C
1-20
alkyl)
0-1
-aryl;
—O—(C
1-20
alkyl)
0-1
-heteroaryl;
—O—(C
1-20
alkyl)
0-1
-heterocyclyl;
—C
1-20
alkoxycarbonyl;
—S(O)
0-2
—C
1-20
alkyl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-aryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heteroaryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heterocyclyl;
—N(R
3
)
2
;
—N
3
;
oxo;
-halogen;
—NO
2
;
—OH; and
—SH; and
—C
1-20
alkyl-NR
3
—Q—X—R
4
or —C
2-20
alkenyl-NR
3
—Q—X—R
4
wherein Q is —CO— or —SO
2
—; X is a bond, —O— or —NR
3
— and R
4
is aryl; heteroaryl; heterocyclyl; or —C
1-20
alkyl or C
2-20
alkenyl that is unsubstituted or substituted by one or more substituents selected from the group consisting of:
-aryl;
-heteroaryl;
-heterocyclyl;
—O—C
1-20
alkyl;
—O—(C
1-20
alkyl)
0-1
-aryl;
—O—(C
1-20
alkyl)
0-1
-heteroaryl;
—O—(C
1-20
alkyl)
0-1
-heterocyclyl;
—C
1-20
alkoxycarbonyl;
—S(O)
0-2
—C
1-20
alkyl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-aryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heteroaryl;
—S(O)
0-2
—(C
1-20
alkyl)
0-1
-heterocyclyl;
—N(R
3
)
2
;
—NR
3
—CO—O—C
1-20
alkyl;
—N
3
;
oxo;
-halogen;
—NO
2
;
—OH; and
—SH; or R
4
is
wherein Y is —N— or —CR—;
R
2
is selected from the group consisting of:
-hydrogen;
—C
1-10
alkyl;
—C
2-10
alkenyl;
-aryl
—C
1-10
alkyl-O—C
1-10
-alkyl;
—C
1-10
alkyl-O—C
2-10
alkenyl; and
—C
1-10
alkyl or C
2-10
alkenyl substituted by one or more substituents selected from the group consisting of: —OH;
-halogen;
—N(R
3
)
2
;
—CO—N(R
3
)
2
;
—CO—C
1-10
alkyl;
—N
3
;
-aryl;
-heteroaryl;
-heterocyclyl;
—CO-aryl; and
—CO-heteroaryl;
each R
3
is independently selected from the group consisting of hydrogen and C
1-10
alkyl; and
each R is independently selected from the group consisting of hydrogen, C
1-10
alkyl, C
1-10
alkoxy, halogen and trifluorome
3M Innovative Properties Company
Aulakh Charanjit S.
Ersfeld Dean A.
LandOfFree
2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]&lsqb... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]&lsqb..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]&lsqb... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3331112