Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-02-08
2003-11-25
Rao, Deepak (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S292000, C544S126000, C546S081000
Reexamination Certificate
active
06653304
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compounds and compositions comprising cannabinoid receptor modulators, to processes for preparing such compounds and compositions, and to the use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases.
BACKGROUND OF THE INVENTION
Delta-9 THC, the principle active component of marijuana, is a member of a large family of lipophilic compounds (i.e., cannabinoids) that mediate physiological and psychotropic effects including immunosuppression, analgesia, inflammation, emesis, and intraocular pressure. Cannabinoids work through selective binding to G-protein coupled cannabinoid receptors. Two types of cannabinoid receptors have been cloned including CB1 (L. A. Matsuda et al.
Nature,
Vol. 346 [1990], pp. 561-564), and CB2 (S. Munro et al,
Nature,
Vol. 365 [1993], pp. 61-65). The CB1 receptor is found mainly on cells of the central nervous system, while the CB2 receptor is found mainly on cells of the peripheral nervous system including cells comprising the immune system such as lymphoid cells.
Compounds that reportedly bind to the cannabinoid G-protein receptors are disclosed in European Patent Documents Nos. EP 0570920 and EP 0444451; International Publications Nos. WO 97/29079, WO 99/02499, WO 98/41519, and WO 9412466; U.S. Pat. Nos. 4,371,720, 5,081,122, 5,292,736, and 5,013,387; and French Patent No. FR 2735774, each of which is incorporated herein by reference.
SUMMARY OF THE INVENTION
Applicants have discovered that cannabinoid receptor modulators including cannabinoid receptor agonists are useful in treating respiratory disease, such as chronic pulmonary obstructive disorder, emphysema, asthma, and bronchitis. In one aspect of the invention, there is provided the use of cannabinoid receptor modulators in treating respiratory disease in a mammal comprising administering to said mammal an effective amount of at least one cannabinoid receptor modulator. Advantageously, the cannabinoid receptor modulator for this aspect of the invention is a CB2-receptor modulator.
The present invention is also directed to compounds and pharmaceutical compositions comprising at least one cannabinoid receptor modulator, and to the use of at least one such compound in treating respiratory and non-respiratory leukocyte activation-associated disorders, wherein the compound has the formula (I):
or a pharmaceutically-acceptable salt or hydrate thereof, in which:
A and B are selected from carbon and nitrogen so that ring X defines a pyrrole, pyrazole, or imidazole ring; wherein when A is nitrogen, the group —C(═O)NR
1
R
2
is attached to atom C-3 and R
5
does not exist; and when A is carbon, one of the group —C(═O)NR
1
R
2
and R
5
is attached to A and the other of —C(═O)NR
1
R
2
and R
5
is attached to atom C-3; and when B is carbon, two R
4
groups attached to B and atom C-5, respectively, optionally form a fused 6-membered aryl or 6-membered heteroaryl having one heteroatom which is nitrogen, wherein said aryl or heteroaryl has three or four groups R
6
;
f is 0 or 1;
g is 1 or 2;
R
1
and R
2
are independently selected from hydrogen, alkyl, substituted alkyl, heterocycloalkyl, cycloalkyl, aryl, and heterocyclo; or R
2
together with R
1
or R
5
forms a five or six membered heterocyclo;
R
3
is hydrogen, alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heterocyclo, or alkoxy, or forms a heterocyclo with one of R
6
;
R
4
is attached to atom C-5 and optionally B and at each occurrence independent of each other R
4
is selected from hydrogen, alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heterocyclo, hydroxy, alkoxy, amino, aminoalkyl, cyano, halogen, alkylamide, NR
8
C(═O)R
9
, and S(O)
u
R
10
; or when B is carbon, optionally two R
4
groups taken together form a six-membered aryl or heteroaryl having three or four R
6
;
R
5
is attached to A or atom C-3 and is hydrogen, alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkoxy, aryl, or heterocyclo; or R
5
together with R
2
forms a heterocyclo;
R
6
at each occurrence independent of each other R
6
is selected from hydrogen, alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, cycloalkyl, substituted aryl, heterocyclo, hydroxy, alkoxy, amino, aminoalkyl, cyano, halogen, alkylamide, nitro, NR
8
C(═O)R
9
, S(O)
u
R
10
, —C(═O)R
8
, —CO
2
R
8
, —S(O)
2
NR
8
R
10
, —C(═O)N(R
8
)O(R
9
), —C(═O)NR
8
R
9
, and —OC(═O)R
10
; and/or one R
6
group together with R
3
forms a heterocyclo;
R
8
and R
9
at each occurrence independent of each other R
8
and R
9
are selected from hydrogen, alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, and heterocyclo; or R
8
and R
9
together form a three-to-eight membered heterocyclo; or R
8
together with R
10
forms a three-to-eight membered heterocyclo; and
R
10
at each occurrence independent of each other R
10
is selected from alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkynyl, or forms a heterocyclo with R
8
; and u is 0, 1, 2 or 3.
According to another aspect of the invention, there are provided pharmaceutical compositions useful for treating respiratory disease comprising an effective amount of at least one cannabinoid receptor modulator according to formula (I) in a pharmaceutically-acceptable carrier or modulator. In a further aspect of the invention, there are provided compounds useful as cannabinoid receptor modulators and pharmaceutical compositions comprising such cannabinoid receptor modulators, wherein the compounds comprise selected compounds according to formula (I), as defined hereinafter. In a still further aspect of the invention, there is provided a process of preparing one or more intermediates to compounds of formula (I), and processes for preparing compounds of formula (I).
DETAILED DESCRIPTION OF THE INVENTION
The following are definitions of terms used in this specification. The initial definition provided for a group or term herein applies to that group or term throughout the present specification, individually or as part of another group, unless otherwise indicated.
The term “alkyl” refers to straight or branched chain hydrocarbon groups having 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms. The expression “lower alkyl” refers to alkyl groups of 1 to 4 carbon atoms.
The term “substituted alkyl” refers to an alkyl group as defined above having one, two or three substituents selected from the group consisting of halo, cyano, nitro, amino, aminoalkyl, hydroxy, OR
a
, —SH, keto (═O), —C(═O)H, —CO
2
H, —C(═O)(R
a
), —CO
2
(R
a
), —SO
3
H, —S(O)
0-2
(R
a
), —S(O)
2
NR
a
R
b
, —C(═O)N(R
a
)O(R
b
), —C(═O)N(R
a
)
2
, —OC(═O)R
a
, cycloalkyl, or aryl, wherein at each occurrence each of the groups R
a
, R
b
are independently selected from alkyl, substituted alkyl, heterocycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, and heterocyclo; or R
a
and R
b
taken together form a three-to-eight membered heterocyclo.
When the term “alkyl” is used to suffix another group, such as in “aryl
alkyl
”, “heterocyclo
alkyl
” or cycloalkyl
alkyl
,” the term defines with more specifity at least one of the groups that a substituted alkyl will contain. In other words, in these instances the specifically-named groups are bonded directly through a substituted or unsubstituted alkyl chain as defined above. For example, an arylalkyl includes benzyl, and a heterocycloalkyl includes ethyl-morpholino or any other straight or branched hydrocarbon chain of 1 to 12 carbon atoms having a substituted or unsubstituted heterocyclo as one of its substituents.
The term “alkenyl” refers to straight or branched chain hydrocarbon groups of 2 to 10, pre
Chen Ping
Hynes John
Leftheris Katerina
Tokarski John
Wrobleski Stephen
Bristol-Myers Squibb Co.
Duncan Laurelee A.
Rao Deepak
Winslow Anastasia P.
LandOfFree
Cannabinoid receptor modulators, their processes of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cannabinoid receptor modulators, their processes of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cannabinoid receptor modulators, their processes of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3149080