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N-(4-piperidinyl) (dihydroxybenzofuran or dihydro-2H-benzopyran)carboxamide derivatives

  • US 5,262,418 A
  • Filed: 11/17/1992
  • Issued: 11/16/1993
  • Est. Priority Date: 03/06/1990
  • Status: Expired due to Term
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First Claim
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1. A compound of the formula:

  • ##STR126## an N-oxide form, a salt or a sterochemically isomeric form thereof, wherein;

    A is a radical of the formula;

    

    space="preserve" listing-type="equation">--CH.sub.2 --CH.sub.2 --                                   (a-1),
    

    space="preserve" listing-type="equation">--CH.sub.2 --CH.sub.2 --CH.sub.2 --                        (a-2), or
    

    space="preserve" listing-type="equation">--CH.sub.2 --CH.sub.2 --CH.sub.2 --CH.sub.2 --             (a-3), wherein one or two hydrogem atoms in said radicals (a-1) to (a-3) may be replaced by a C1-6 alkyl radical;

    R1 is hydrogen or halo;

    R2 is hydrogen, amino, mono- or di(C1-6 alkyl)amino or C1-6 alkylcarbonylamino;

    R3 is hydrogen or C1-6 alkyl;

    L is C3-6 cycloalkyl, C5-6 cycloalkanone, C3-6 alkenyl optionally substituted with aryl, or L is a radical of the formula;

    

    space="preserve" listing-type="equation">--Alk--X--R.sup.5                                          (b-

         2),
    

    space="preserve" listing-type="equation">--Alk--Y--C(═

    O)--R.sup.7                               (b-

         3), or
    

    space="preserve" listing-type="equation">--Alk--Y--C(═

    O)--NR.sup.9 R.sup.10                     (b-

         4), wherein each Alk is C1-6 alkanediyl;

    R5 is hydrogen, C1-6 alkyl, hydroxyC1-6 alkyl, C3-6 cycloalkyl, aryl or Het;

    X is O, S, SO2 or NR6 said R6 being hydrogen, C1-6 alkyl or aryl;

    R7 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, aryl, arylC1-6 alkyl, di(aryl)methyl, C1-6 alkyloxy or hydroxy;

    Y is NR8 or a direct bond, said R8 being hydrogen, C1-6 alkyl or aryl;

    R9 and R10 each independently are hydrogen, C1-6 alkyl, C3-6 cycloalkyl, aryl or arylC1-6 alkyl, orR9 and R10 combined with the nitrogen atom bearing R9 and R10 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C1-6 alkyl, amino or mono- or di(C1-6 alkyl)amino, orR9 and R10 combined with the nitrogen atom bearing R9 and R10 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C1-6 alkyl;

    wherein in the foregoing;

    aryl represents unsubstituted phenyl or phenyl substituted with 1, 2 or 3 substituents each independently selected from halo, hydroxy, C1-6 alkyl, C1-6 alkyloxy, aminosulfonyl, C1-6 alkylcarbonyl, nitro, trifluoromethyl, amino or aminocarbonyl; and 

    (I) Het represents a group of the formula;

     ##STR127## wherein;

     m is 1 or 2;

    each X1 and X2 independently represents O or S;

    each R11 represents hydrogen, C1-4 alkyl, C1-4 alkyloxyC1-4 alkyl or hydroxyC1-4 alkyl; and 

    R12 represents hydrogen, halo or C1-4 alkyl, or(II) Het represents a cyclic ether selected from the group consisting of 1,3-dioxolanyl optionally substituted with C1-4 alkyl;

     1,3-dioxanyl optionally substituted with C1-4 alkyl;

     tetrahydrofuranyl optionally substituted with C1-4 alkyl;

     tetrahydropyranyl optionally substituted with C1-4 alkyl;

     2,3-dihydro-1,4-benzodioxinyl;

     2,3-dihydrobenzofuran and 3,4-dihydro-1(2H)-benzopyranyl;

     or(III) Het represents a member selected from the group consisting of pyrrolidinyl;

     piperidinyl;

     pyridinyl which is optionally substituted with one or two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, trifluoromethyl, C1-6 alkyloxy, aminocarbonyl, mono and di(C1-6 alkyl)aminocarbonyl, amino, mono and di(C1-6 alkyl)amino and C1-6 alkyl-oxycarbonyl;

     pyrimidinyl which is optionally substituted with one or two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino and mono and di(C1-6 alkyl)amino;

     pyridazinyl which is optionally substituted with C1-6 alkyl or halo;

     pyrazinyl which is optionally substituted with one ore two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino, mono- and di(C1-6 alkyl)amino and C1-6 alkyloxy-carbonyl;

     pyrrolyl which is optionally substituted with C1-6 alkyl;

     pyrazolyl which is optionally substituted with C1-6 alkyl;

     imidazolyl which is optionally substituted with C1-6 alkyl;

     triazolyl which is optionally substituted with C1-6 alkyl;

     quinolinyl optionally substituted with up to two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino, mono and di(C1-6 alkyl)amino and trifluoromethyl;

     isoquinolinyl optionally substituted with up to two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino, mono and di(C1-6 alkyl)amino and trifluoromethyl;

     quinoxalinyl optionally substituted with up to two substituents each independently selected from C1-6 alkyl, hydroxy, halo, cyano and C1-6 alkyloxy;

     quinazolinyl optionally substituted with C1-6 alkyl;

     benzimidazolyl optionally substituted with C1-6 alkyl;

     indolyl optionally substituted with C1-6 alkyl;

     5,6,7,8-tetrahydroquinolinyl optionally substituted with up to two substituents each independently selected from halo, hydroxy, cyano, C1-6 alkyl, C1-6 alkyloxy, amino, mono- and di(C1-6 alkyl)amino and trifluoromethyl;

     5,6,7,8-tetrahydro-quinoxalinyl optionally substituted with up to two substituents each independently selected from C1-6 alkyl;

     hydroxy, halo, cyano and C1-6 alkyloxy;

     thiazolyl optionally substituted with C1-6 alkyl;

     oxazolyl optionally substituted with C1-6 alkyl;

     benzoxazolyl optionally substituted with C1-6 alkyl; and 

     benzothiazolyl optionally substituted with C1-6 alkyl;

    (IV) Het represents a group of the formula;

     ##STR128## X3 is O or S;

     R13 is hydrogen, C1-6 alkyl or arylC1-6 alkyl;

    R14 is hydrogen, halo, C1-6 alkyl or aryl;

    G1 is --CH2 --CH2 --, --CH═

    CH--, --N═

    N--, --C(═

    O)--CH2 -- or --CH2 --CH2 --CH2 --, wherein one or two hydrogen atoms each independently may be replaced by C1-6 alkyl; and 

    G2 is --CH2 --CH2 --, --CH2 --N(R13)-- or --CH2 --CH2 --CH2 --, wherein one or two hydrogen atoms each independently may be replaced by C1-6 alkyl;

     or(V) Het represents a group of the formula;

     ##STR129## wherein X4 and X5 each independently are O or S;

     each R15 independently is hydrogen, C1-6 alkyl or arylC1-6 -alkyl;

    each R16 independently is hydrogen, halo, C1-6 alkyl or C1-6 alkyloxy;

    R17 is hydrogen, halo, C1-6 alkyl or aryl; and 

    each R18 independently is hydrogen, C1-6 alkyloxy or C1-6 alkyl,G3 is --CH═

    CH--CH═

    CH--, --(CH2)4 --, --S--(CH2)2 --, --S--(CH2)3 --, --S--CH═

    CH--, --CH═

    CH--O--, --NH--(CH2)2 --, --NH--(CH2)3 --, --NH--CH═

    CH--, --NH--N═

    CH--CH2 --, --NH--CH═

    N-- or --NH--N═

    CH--; and 

    G4 is --CH═

    CH--CH═

    CH--, --CH═

    CCl--CH═

    CH--, --CCl═

    CH--CH═

    CH--, --N═

    CH--CH═

    CH--, --CH═

    N--CH═

    CH--, --CH═

    CH--N═

    CH--, --CH═

    CH--CH═

    N--, --N═

    CH--N═

    CH-- or --CH═

    N--CH═

    N--,wherein the radicals (d-5), (d-6), (d-7) and (d-8) may be connected to Alk by replacing either a hydrogen or a radical R15 or R16 by a free bond.

      

    

  

  
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