Carbazole derivatives and their use as 5HT-induced antagonists

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514212, 514323, 546200, 540602, 548336, 548439, A61K 3140, A61K 31415, C07D40306, C07D40106

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active

047256150

ABSTRACT:
The invention relates to compounds of the general formula (I): ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4)-alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-(C.sub.1-3)alkyl group;
one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl-(C.sub.1-3)alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; and X represents a halogen atom or a hydroxy, C.sub.1-4 alkoxy, phenyl-(C.sub.1-3)-alkoxy or C.sub.1-6 alkyl group or a group NR.sup.5 R.sup.6 or CONR.sup.5 R.sup.6 wherein R.sup.5 and R.sup.6, which may be the same or different, each represents a hydrogen atom or a C.sub.1-4 alkyl or C.sub.3-4 alkenyl group, or together with the nitrogen atom to which they are attached form a saturated 5 to 7 membered ring; and physiologically acceptable salts and solvates thereof.
The compounds are potent and selective antagonists of "neuronal" 5-hydroxytryptamine receptors and are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania;); anxiety, pain; gastric stasis; symptoms of gastrointestinal dysfunction such as occur with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence; migraine; and nausea and vomiting.

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R. Littell, E. N. Greenblatt and G. R. Allen, Jr., J. Med. Chem. 15(8) 875-6, 1972.
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J. C. Lancelot, et al., Chem. & Pharm. Bul., 1983, 31, 2652-2661.
Y. Oikawa et al., J. Org. Chem., 1977, 42, 1213-1216.

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