Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-04-06
1995-02-28
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540578, 540579, C07D48704, A61K 3155
Patent
active
053937538
DESCRIPTION:
BRIEF SUMMARY
SUMMARY OF THE INVENTION
The invention relates to compounds of the formula: ##STR2##
wherein R.sup.1 is H, C.sub.1 -C.sub.7 alkyl, C.sub.3 -C.sub.7 cycloalkyl, CF.sub.3, aryl, substituted aryl, heteroaryl, -O-C.sub.1 -C.sub.7 alkyl, or -O-C.sub.3 -C.sub.7 cycloalkyl; R.sup.2 and R.sup.3 are each independently H, C.sub.1 -C.sub.7 alkyl, C.sub.3 -C.sub.7 cycloalkyl, CF.sub.3, NO.sub.2, halogen, OR.sup.7, NR.sup.8 R.sup.9 or S(O).sub.m R.sup.10, wherein m is 0, 1 or 2; R.sup.4 is H, C.sub.1 -C.sub.7 alkyl, arylmethyl, or substituted arylmethyl; R.sup.5 and R.sup.6 are each independently H, C.sub.1 -C.sub.7 alkyl, C.sub.3 -C.sub.7 cycloalkyl, aryl, substituted aryl, heteroaryl, arylmethyl, substituted arylmethyl, or taken together constitute a chain of (CH.sub.2).sub.k groups, wherein k is 3, 4, or 5; R.sup.7, R.sup.8 and R.sup.9 are each independently H, C.sub.1 -C.sub.7 alkyl, -C(.dbd.O)-(C.sub.1 -C.sub.7 alkyl), -C(.dbd.O)aryl, or -C(.dbd.O)heteroaryl; R.sup.10 is C.sub.1 -C.sub.7 alkyl, C.sub.3 -C.sub.7 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylmethyl, or substituted arylmethyl; one and only one of the dotted lines, a, b, c, and d, represents a carbon-carbon bond; n is 0, 1, 2, or 3; Z is O or S, Q is CH, N or NO, with the proviso that Z is not S when Q is NO, or pharmaceutically acceptable acid addition salts thereof.
Preferred compounds of formula 1.0 are those wherein one and only one of the dotted lines a and b is a carbon-carbon bond and Q is CH.
More preferred are compounds of formula 1.0 wherein the dotted line b represents a carbon-carbon bond; Q is CH; R.sup.1 is H, C.sub.1 -C.sub.7 alkyl or heteroaryl; R.sup.2 is H or halogen; R.sup.3 is H or halogen; R.sup.4 is H; R.sup.5 and R.sup.6 are each H; and n is 1.
Of these, compounds wherein Z is O, and R.sup.3 is H are even more preferred. Most preferred are compounds as described just above wherein R.sup.1 is ##STR3## and R.sup.2 is H or chlorine meta to the Q position.
Also preferred are compounds as described just above wherein R.sup.1 is C.sub.1 -C.sub.7 alkyl and R.sup.2 is H or chlorine meta to the Q position.
Also preferred are compounds as described just above wherein R.sup.1 is ##STR4## and R.sup.2 is H or chlorine meta to the Q position.
Still another preferred compound of formula 1.0 is ##STR5##
Exemplary compounds of the invention are: ##STR6##
A most preferred compound of the invention is: ##STR7##
Due to their platelet activating factor(PAF)-antagonist activity, the compounds of formula 1.0 are useful in treating allergic reactions in mammals, e.g. man. In general, the compounds of formula 1.0 may be used to treat any condition in which mediation of PAF is involved,
Specifically, these compounds are useful as agents for the treatment of asthma and other allergic diseases. These compounds are also useful as agents in the treatment of inflammation. In particular, these compounds are useful for the oral treatment of asthma and other allergic diseases and the oral treatment of inflammation.
The invention also relates to pharmaceutical compositions for treating allergic diseases which compose an anti-allergic, ally effective amount of a compound of formula 1.0 and an inert pharmaceutical carder material. The invention also relates to pharmaceutical compositions for treating inflammation which comprise an anti-inflammatory effective amount of a compound of formula 1.0 and an inert pharmaceutical carder material.
The invention also relates to a method for treating allergic diseases which comprises administering to a host in need of such treatment an anti-allergically effective amount of a compound of formula 1.0. The invention also relates to a method for treating inflammation which comprises administering to a host in need of such treatment an anti-inflammatory effective amount of a compound of formula 1.0.
DETAILED DESCRIPTION OF THE INVENTION
Compounds of formula 1.0 of the invention form pharmaceutically acceptable acid addition salts with any of a variety of inorganic and organic acids. Examples of sui
REFERENCES:
patent: 3272826 (1969-03-01), Jucker et al.
patent: 3442903 (1969-05-01), Galantay
patent: 3458522 (1969-07-01), Galantay
patent: 3485846 (1989-12-01), Galantay
patent: 3491103 (1970-01-01), Jucker
patent: 3682930 (1972-08-01), Bourguin et al.
patent: 3770728 (1973-11-01), Bourguin
patent: 3960894 (1976-06-01), Bourguin
patent: 3994915 (1976-11-01), Salmond
patent: 4355036 (1982-10-01), Villani
patent: 4596809 (1986-06-01), Scherlock et al.
patent: 4609664 (1986-09-01), Hasspacker
patent: 4826853 (1989-05-01), Piwinski et al.
patent: 5089496 (1992-02-01), Piwinski et al.
Robey et al, J. Heterocyclic Chem., 26, pp. 779-783 (1989).
Remy et al. J. Med. Chem. (1982), 25, 231-234.
Remy et al. J. Med. chem. (1983), 26 974-980.
Galantay et al., J. Med. Chem. (1974), vol. 17, No. 12, pp. 1316-1327.
Maurer et al., Journal of Chromatography, 430 (1988) 31-41.
Bond Robert T.
Boxer Matthew
Datlow Philip I.
Jeanette Henry C.
Schering Corporation
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