Patent ID: 6331543
Filing Date: 2001-12-18
Classification: A61K,A61P,C07D

Abstract:
A compound of formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XV), formula (XVI), formula (XVII), formula (XVIII), formula (XIX), or a pharmaceutically acceptable salt thereof:wherein the compound of formula (XI) is: ##STR35##whereinD.sub.2 is a hydrogen, a lower alkyl or D;D is:(i) --NO,(ii) --NO.sub.2,(iii) --CH(R.sub.d)--O--C(O)--Y--Z--(C(R.sub.e)(R.sub.f)).sub.p --T--Q,(iv) --C(O)--Y--Z--(G--(C(R.sub.e)(R.sub.f)).sub.b --T--Q).sub.p ;(v) --P--Z--(G--(C(R.sub.e)(R.sub.f)).sub.b --T--Q).sub.p ;(vi) --P.sub.1 --B.sub.1 --W--B.sub.t --L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --E.sub.j --L.sub.g --(C(R.sub.e)(R.sub.f)).sub.z --T--Q; or(vii) --P.sub.1 --F'.sub.n --L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --E.sub.j --L.sub.g --(C(R.sub.e)(R.sub.f)O.sub.z --T--Q;R.sub.d is a hydrogen, a lower alkyl, a cycloalkyl, an aryl or an arylalkyl;Y is oxygen, S(O).sub.o, lower alkyl or NR.sub.i ;o is an integer from 0 to 2;R.sub.i is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an aryl carboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an arylsulfinyl, an arylsulfonyl, a sulfonamido, a carboxamido, a carboxylic ester, --CH.sub.2 --C(T--Q)(R.sub.e)(R.sub.f), or --(N.sub.2 O.sub.2.sup.-).sup.-.multidot.M.sup.+, wherein M.sup.+ in an organic or inorganic cation;R.sub.e and R.sub.f are each independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, a cycloalkylalkyl, a heterocyclicalkyl, an alkoxy, a haloalkoxy, an amino, an alkylamino, a dialkylamino, an arylamino, a diarylamino, an alkylarylamino, an alkoxyhaloalkyl, a haloalkoxy, a sulfonic acid, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an aminoaryl, an alkoxy, an aryl, an arylalkyl, an alkylaryl, a carboxamido, a alkyl carboxamido, an aryl carboxamido, an amidyl, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a urea, a nitro, --T--Q, or (C(R.sub.e)(R.sub.f)).sub.k --T--Q, or R.sub.e and R.sub.f taken together with the carbon atoms to which they are attached are a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group;k is an integer from 1 to 3;p is an integer from 1 to 10;T is independently a covalent bond, oxygen, S(O).sub.o or NR.sub.i ;Z is a covalent bond, an alkyl, an aryl, an arylalkyl, an alkylaryl, a heteroalkyl, or (C(R.sub.e)(R.sub.f)).sub.p ;Q is --NO or --NO.sub.2 ;G is a covalent bond, --T--C(O)--, --C(O)--T--or T;b is an integer from 0 to 5;P is a carbonyl, a phosphoryl or a silyl;l and t are each independently an integer from 1 to 3;r, s, c, d, g, i and j are each independently an integer from 0 to 3;w, x, y and z are each independently an integer from 0 to 10;P.sub.1 is a covalent bond or P;B at each occurrence is independently an alkyl group, an aryl group, or (C(R.sub.e)(R.sub.f)).sub.p ;E at each occurrence is independently --T--, an alkyl group, an aryl group, or --(CH.sub.2 CH.sub.2 O).sub.q ;q is an integer of from 1 to 5;L at each occurrence is independently --C(O)--, --C(S)--,--T--, a heterocyclic ring, an aryl group, an alkenyl group, an alkynyl group, an arylheterocyclic ring, or --(CH.sub.2 CH.sub.2 O).sub.q ;W is oxygen, S(O).sub.o, or NR.sub.i ;F' at each occurrence is independently selected from B or carbonyl;n is an integer from 2 to 5;with the proviso that when R.sub.i is --CH.sub.2 --C(T--Q)(R.sub.e)(R.sub.f) or --(N.sub.2 O.sub.2)M.sup.+, or R.sub.e or R.sub.f are T--Q or (C(R.sub.e)(R.sub.f)).sub.k --T--Q, then the ""--T--Q"" subgroup designated in D can be a hydrogen, an alkyl, an alkoxy, an alkoxyalkyl, an aminoalkyl, a hydroxy, or an aryl; andwith the proviso that at least one D.sub.2 must be D;wherein the compound of formula (XII) is: ##STR36##wherein,R.sub.8 is a hydrogen, a lower alkyl group or a haloalkyl group;J is: ##STR37##R.sub.24 is hydrogen or K--G--D;K is: ##STR38##G.sub.3 is (CH), (CH.sub.2), oxygen, sulfur or nitrogen;V is carbon or nitrogen;A.sub.1, A.sub.2 and A.sub.3 comprise the other subunits of a 5- or 6-membered monocyclic aromatic ring and each is independently (i) C--R.sub.23 wherein R.sub.23 at each occurrence is independently D, a hydrogen, a halogen, an alkoxy, a nitrile, an alkyl, an arylalkyl, an alkylaryl, a carboxamido, a carboxyl, a haloalkyl, an alkoxyalkyl, an alkoxyaryl or a nitro; (ii) sulfur; (iii) oxygen; and (iv) B.sub.a.dbd.B.sub.b wherein B.sub.a and B.sub.b are each independently nitrogen or C--R.sub.23 wherein R.sub.23 at each occurrence is as defined herein; andR.sub.26, R.sub.27, R.sub.28, R.sub.29, and R.sub.30 are each independently a hydrogen, a halogen, a hydroxy, a haloalkyl, an alkoxy, an alkoxyalkyl, an alkoxyaryl, an alkoxyhaloalkyl, a nitrile, a nitro, an alkyl, an alkylaryl, an arylalkyl, a hydroxy alkyl, a carboxamido, or a carboxyl;d, g, p, E, L, G, T, Y and D are as defined herein;with the proviso that at least one of the variables A.sub.1, A.sub.2, A.sub.3, J or R.sub.24 must contain the element ""--T--Q"" or ""D"";wherein the compound of formula (XIII) is: ##STR39##wherein,R.sub.31 is an alkyl, a halogen, a haloalkyl, or a haloalkoxy;R.sub.32 is D, or --C(O)--R.sub.8 ;D.sub.1 is D or hydrogen; and D and R.sub.8 are as defined herein;wherein the compound of formula (XIV) is: ##STR40##whereinA is CH.sub.2, a carbonyl or a methanethial;G.sub.4 is oxygen or sulfur;R.sub.34 is hydrogen, lower alkyl, alkenyl, alkynyl or L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --L.sub.j --E.sub.g --(C(R.sub.e)(R.sub.f)).sub.z --T--Q; R.sub.35 and R.sub.36 are each independently a hydrogen, a lower alkyl, an arylalkyl, an alkylaryl, a cycloalkylalkyl, a heterocyclicalkyl, T--Q or (C(R.sub.e)(R.sub.f)).sub.k --T--Q; or R.sub.35 and R.sub.36 taken together with the carbon to which they are attached are a carbonyl group, a methanethial group, a heterocyclic group or a cycloalkyl group; or R.sub.34 and R.sub.35 taken together with the carbon to which they are attached are (C(R.sub.g)(R.sub.h)).sub.u or --C(R.sub.g)(R.sub.h)--C(R.sub.g).dbd.C(R.sub.g)--(C(R.sub.g)(R.sub.h)). sub.v wherein u is an integer of 3 or 4, v is an integer of 1 or 2 and R.sub.g and R.sub.h at each occurrence is independently a hydrogen, an alkyl, T--Q or (C(R.sub.e)(R.sub.f)).sub.k --T--Q;R.sub.36 is a hydrogen, a halogen or a lower alkyl;R.sub.37 is: ##STR41##D.sub.1 is D or hydrogen;c, d, g, i, j, k, r, s, w, x, y, z, E, L, G.sub.3, T, Q, R.sub.e, R.sub.f, R.sub.26, R.sub.27, R.sub.28, R.sub.29, R.sub.30 and R.sub.38 are a defined herein;with the proviso that D.sub.1 must be D if R.sub.34, R.sub.35, R.sub.36 or R.sub.37 do not contain the element ""T--Q"";wherein the compound of formula (XV) is: ##STR42##whereinR.sub.25 at each occurrence is independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an amino an alkoxy, an aryl, an arylalkyl, a carboxamido, a alkyl carboxamido, an aryl carboxamido, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a carboxamido, an alkylcarboxamido, an arylcarboxamido, a haloalkoxy, a sulfonamido, a urea, a nitro, or L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --E.sub.j --L.sub.g --(C(R.sub.e)(R.sub.f)).sub.z --T--Q;c, d, g, i, j, k, r, s, w, x, y, z, G.sub.4, D.sub.1, E, L, T, Q, R.sub.e, R.sub.f, R.sub.37 and R.sub.38 are as defined herein;with the proviso that D.sub.1 must be D if R.sub.e or R.sub.25 do not contain the element ""T--Q"";wherein the compound of formula (XVI) is: ##STR43##whereinR.sub.40 is a hydrogen, a lower alkyl, a haloalkyl, a halogen, an alkoxy, an alkenyl, an alkynyl, a carbamoyl, a sulfonamido or L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --E.sub.j --L.sub.g --(C(R.sub.e)(R.sub.f)).sub.z --T--Q;R.sub.4, is a lower alkyl, a hydroxyalkyl, an alkylcarboxylic acid, an alkylcarboxylic ester an alkylcarboxamido or L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --E.sub.j --L.sub.g --(C(R.sub.e)(R.sub.f)).sub.z --T--Q; andR.sub.42 is: ##STR44##R.sub.43 at each occurrence is independently an amino, a cyano, a halogen, a nitro group, a carboxyl, a carbamoyl, a sulfonic acid, a sulfonic ester, a sulfonamido, a heterocyclic ring, a carboxamido, a carboxylic ester, an ester, an amidyl, a phosphoryl or L.sub.r --E.sub.s --(C(R.sub.e)(R.sub.f)).sub.w --E.sub.c --(C(R.sub.e)(R.sub.f)).sub.x --L.sub.d --(C(R.sub.e)(R.sub.f)).sub.y --L.sub.i --E.sub.j --L.sub.g --(C(R.sub.e)(R.sub.f)).sub.z --T--Q; andc, d, g, i, j, k, r, S, w, x, y, z, E, L, T, Q, R.sub.e, and R.sub.f are as defined herein;with the proviso that at least one of R.sub.40, R.sub.4, or R.sub.43 must contain the element ""T--Q"";wherein the compound of formula (XVII) is: ##STR45##wherein R.sub.8, R.sub.23, R.sub.24 p and J are as defined herein;with the proviso that at least one R.sub.24 or J must contain the element ""--T--Q"" orwherein the compound of formula (XVIII) is: ##STR46##wherein R.sub.44 is: ##STR47##wherein d, g, p, D, E, L, G.sub.3, G.sub.4, T, R.sub.8, R.sub.26, R.sub.27, R.sub.8, R.sub.29, and R.sub.30 are as defined herein;wherein the compound of formula (XIX) is: ##STR48##wherein,R.sub.46 and R.sub.47 are each independently a lower alkyl, hydroxyalkyl or D, or R.sub.46 and R.sub.47 taken together with the nitrogen atom to which they are attached are a heterocyclic ring,G.sub.4, T, R.sub.8, and k are as defined herein;with the proviso that at least one of the variables R.sub.46 or R.sub.47 must be D or when the variables taken together are a heterocyclic ring, the ring must contain NR.sub.i, wherein R.sub.1 must contain the element ""T--Q"".