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Pharmaceutical agents for treatment of emesis

  • US 5,393,762 A
  • Filed: 06/04/1993
  • Issued: 02/28/1995
  • Est. Priority Date: 06/04/1993
  • Status: Expired due to Term
First Claim
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1. A method of treating or preventing emesis in a mammal, comprising administering to said mammal an amount of a compound of the formula ##STR58## wherein X1 is hydrogen, (C1 -C10)alkoxy optionally substituted with from one to three fluorine atoms or (C1 -C10) alkyl optionally substituted with from one to three fluorine atoms;

  • X2 and X3 are independently selected from hydrogen, halo, nitro, (C1 -C10)alkyl optionally substituted with from one to three fluorine atoms, (C1 -C10)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl hydroxy, phenyl, cyano, amino, (C1 -C6)-alkylamino, di-(C1 -C6)alkylamino, ##STR59## hydroxy(C1 -C6)alkyl, (C1 -C4)alkoxy(C1 -C4)alkyl, ##STR60## and R3 is a group of the formula ##STR61## wherein X4 is (CH2)q wherein q is an integer from 2 to 4;

    m is O;

    R16 is hydrogen;

    R17 is absent;

    R12 is a radical selected from hydrogen, (C1 -C6) straight or branched alkyl, (C3 -C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur;

    aryl selected from biphenyl, phenyl, indanyl and naphthyl;

    heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl;

    phenyl-(C2 -C6)alkyl, benzhydryl and benzyl, wherein the point of attachment on R12 is a carbon atom unless R12 is hydrogen, and wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl-(C2 -C6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1 -C10)alkyl optionally substituted with from one to three fluorine atoms, (C1 -C10)alkoxy optionally substituted with from one to three fluorine atoms, amino, hydroxy-(C1 -C6)alkyl, (C1 -C6)alkoxy-(C1 -C6)alkyl, (C1 -C6)-alkylamino, ##STR62## and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl;

    R13 is hydrogen, phenyl or (C1 -C6)alkyl;

    or R12 and R13, together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms wherein one of said carbon atoms that is neither the point of attachment of the spiro ring nor adjacent to it may optionally be replaced by oxygen, nitrogen or sulfur;

    R14 and R15 are each independently selected from hydrogen, hydroxy, halo, amino, oxo (═

    O ), cyano, hydroxy-(C1 -C6)alkyl, (C1 -C6)alkoxy-(C1 -C6)alkyl, (C1 -C6)alkylamino, di-(C1 -C6)alkylamino, ##STR63## and the radicals set forth in the definition of R12 ;

    with the proviso that (a) when R14 and R15 are attached to the same carbon atom, then either each of R14 and R15 is independently selected from hydrogen, fluoro, (C1 -C6)alkyl, hydroxy-(C1 -C6)alkyl and (C1 -C6)alkoxy-(C1 -C6)alkyl, or R14 and R15, together with the carbon to which they are attached, form a (C3 -C6) saturated carbocyclic ring that forms a spiro compound with the nitrogen-containing ring to which they are attached;

    (b) R12 and R13 cannot both be hydrogen;

    (c) when R14 or R15 is attached to a carbon atom of X4 that is adjacent to the ring nitrogen, then R14 or R15, respectively, must be a substituent wherein the point of attachment is a carbon atom; and

    (d) neither R14 , R15 can form a ring with R13 ;

    or a pharmaceutically acceptable salt thereof, effective in treating or preventing such condition.

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