Semicarbazones having CNS activity and pharmaceutical preparations containing same
AssigneeUniversity of Saskatchewan
InventorJonathan Richard Dimmock
Life of this patent
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Abstract
A compound of general formula I below useful as an anticonvulsant for disorders of the central nervous system: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be the same or different and each represents a hydrogen or halogen atom, or a C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl, cyano, C.sub.1-9 alkoxy or C.sub.6-10 aryloxy group; R.sup.5 represents a hydrogen atom or a C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl or C.sub.6-10 aryl group; and X is oxygen or sulfur; or a pharmaceutically-acceptable salt thereof. The compound may be adimistered orally for treating convulsions in humans or animals.
Claims15
A compound of the general formula I:
- ##STR7## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be the same or different and each represents hydrogen, halo, C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl, cyano, C.sub.1-9 alkoxy or C.sub.6-10 aryloxy;
- R.sup.5 represents hydrogen, C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl or C.sub.6-10 aryl;
- and X is oxygen or sulfur;
- with the proviso that:
- a) if X is sulfur, then at least one of R.sup.1 and R.sup.2 is other than hydrogen or at least one of R.sup.3 and R.sup.4 is fluoro, C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl, cyano, C.sub.1-9 alkoxy or C.sub.6-10 aryloxy;
- and
- b) if X is oxygen, R.sup.5 is hydrogen, methyl, or ethyl, and if one of R.sup.1 and R.sup.2 is chloro or methoxy or if one of R.sup.3 and R.sup.4 is methyl, then the other of R.sup.1 and R.sup.2 or the other of R.sup.3 and R.sup.4 is other than hydrogen;
- and
- c) if X is oxygen, R.sup.5 is hydrogen, methyl or ethyl, and if R.sup.1 and R.sup.2 are both hydrogen, then at least one of R.sup.3 and R.sup.4 is other than hydrogen and methyl;
- or a pharmaceutically acceptable salt thereof.
4-(4'-Fluorophenoxy)benzaldehyde semicarbazone or a pharmaceutically-acceptable salt thereof.
A method of preparing a compound of general formula I:
- ##STR8## wherein:
- R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be the same or different and each represents a hydrogen or halogen atom, or a C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl, cyano, C.sub.1-9 alkoxy or C.sub.6-10 aryloxy group;
- R.sup.5 represents a hydrogen atom or a C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl or C.sub.6-10 aryl group;
- and X is oxygen or sulfur;
- except that R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 may not all be hydrogen;
- which method comprises forming an intermediate aryloxy- or arylthio-benzaldehydes or ketones by reacting a corresponding (thio)phenol with fluorobenzaldehyde or a fluoroaryl ketone in a solvent in the presence of potassium carbonate at temperatures in the range of 100.degree. to 200.degree. C. under a non-oxidizing gas, extracting the intermediate and then reacting the intermediate with semicarbazide and collecting the resulting precipitate of the desired compound.
A method of treating a human or animal patient for a disorder of the central nervous system, comprising administering to said patient an effective amount of a compound having the general formula I:
- ##STR9## wherein:
- R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be the same or different and each represents hydrogen, halo, C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl, cyano, C.sub.1-9 alkoxy or C.sub.6-10 aryloxy;
- R.sup.5 represents hydrogen, C.sub.1-9 alkyl, C.sub.3-9 cycloalkyl or C.sub.6-10 aryl;
- and X is oxygen or sulfur;
- with the proviso that;
- a) at least one of R.sup.1, R.sup.2, R.sup.3 or R.sup.4 is other than hydrogen, or
- b) R.sup.5 is other than hydrogen, methyl and ethyl;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.