Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1995-05-24
1997-03-11
McKane, Joseph
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
540597, 540599, 540602, 540607, C07D40506, A61K 3155
Patent
active
056102950
DESCRIPTION:
BRIEF SUMMARY
This application is a National Stage filing under 35 U.S.C. .sctn. 372 of PCT/GB94/00372, filed Feb. 25, 1994.
This invention relates to novel amide derivatives, to processes for their preparations, to their use and to pharmaceutical compositions containing them. The novel compounds act on the central nervous system by binding to 5-HT receptors (as more fully explained below) and hence can be used as medicaments for treating humans and other mammals.
EP-A-0481744 discloses that 2,3,4,5,6,7-hexahydro 1-{4-[1-[4-(2-methoxyphenyl)piperazinyl]]-2-phenylbutyryl}-1H-azepine and its salts are 5-HT.sub.1A binding agents useful, for example as anxiolytics.
The novel compounds of the invention are those of general formula (I)
In formula (I)
each R is independently hydrogen or lower alkyl,
R.sup.1 is hydrogen or lower alkyl,
R.sup.2 is lower alkyl, cycloalkyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl,
or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are both attached represent an azetidino, pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino ring which may be optionally substituted by one or more lower alkyl, aryl or aryl(lower)alkyl groups,
R.sup.3 is an aryl or heteroaryl radical,
R.sup.4 is hydrogen or lower alkyl,
and R.sup.5 is a group of formula ##STR1## where X is --(CH.sub.2).sub.n --, --OCH.sub.2 -- or --SCH.sub.2 --, m is 0 or 1, n is 1, 2 or 3 and p is 0 or 1 such that (m+p) is 1 and that (m+n) is 1, 2 or 3,
R.sup.6 is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, trifluoromethyl, (lower)alkoxycarbonyl, carboxamido, nitro, cyano, amino, (lower)alkylamino, di(lower)alkylamino or (lower) alkylcarbonyl,
R.sup.6' is hydrogen or halogen when X is --(CH.sub.2).sub.n -- and R.sup.6' is hydrogen when X is --OCH.sub.2 -- or --SCH.sub.2 --,
R.sup.7 is hydrogen or lower alkyl or ##STR2## where Y is --O--, --S-- or --CH.sub.2 --,
Z represents a heteroaromatic ring fused on to the non-aromatic ring containing the Y group
and R.sup.6 is as defined above and one or more R.sup.6 groups may be attached to the heteroaromatic ring and/or the non-aromatic ring or ##STR3## where R.sup.6 is as defined above and the indicated 7, 8 positions may optionally be fused with a heteroaromatic ring or a further aromatic ring or
The term "lower" as used herein means that the radical referred to contains 1 to 6 carbon atoms. Preferably such radicals contain 1 to 4 carbon atoms. Examples of "lower alkyl" radicals are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and isopentyl.
Examples of cycloalkyl groups are groups containing 3 to 8 carbon atoms e.g. cyclopentyl, cyclohexyl and cycloheptyl.
When used herein "aryl" means an aromatic radical having 6 to 12 carbon atoms (e.g. phenyl or naphthyl) which optionally may be substituted by one or more substituents. Preferred substituents are lower alkyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy), halogen (e.g. chlorine), halo(lower)alkyl (e.g. trifluoromethyl), nitro, nitrile, amido, (lower)alkoxycarbonyl, amino, (lower)alkylamino and di(lower)alkylamino.
The term "heteroaryl" refers to an aromatic radical containing one or more (e.g. 1, 2 or 3) hetero ring atoms (e.g. oxygen, nitrogen, sulphur) and which may be optionally substituted by one or more substituents. Examples of suitable substituents are given above in connection with "aryl" radicals. The heteroaryl radical may, for example, contain 5 to 10 ring atoms. Unless specified otherwise the heteroaryl radical is preferably mono- or bicyclic. A monocyclic radical may, for example, contain 5 to 7 ring atoms. Preferably the hetero ring contains a nitrogen atom with or without one or more further hetero atoms. Examples of heteroaryl groups include, for example, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl and indolyl each of which may be optionally substituted as mentioned above.
When a "heteroaromatic ring" is fused on to a non-aromatic ring (as in formula B) or is fused on to an aromatic ring (as in formula D) the "heteroaromatic ring" may be a fused "hetero
Cliffe Ian A.
Ifill Anderson D.
Boswell, Jr. R. F.
John Wyeth & Brother Ltd.
McKane Joseph
Myers, Jr. Richard S.
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