Recherche dans les collections de brevets nationales et internationales
Une partie du contenu de cette demande n'est pas disponible pour le moment.
Si cette situation persiste, contactez-nous auObservations et contact
1. (WO1993018035) ANTAGONISTES DES RECEPTEURS DE L'ANGIOTENSINE II
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

CLAIMS

What is claimed is:

1. A compound of the formula:


wherein

A is
(i) a covalent bond,
(ii) -O-,
(iii) -C(O)-,
(iv) -CH2-,
(v) -S-, -S(O)- or-S(O)2-;

E-G is
(i) -N(R5)-,
(ii) -O-, (iii) -S-,
(iv) -N(R5)-CH(R5)-,
(v) -O-CH(R5)-,
(vi) -S-CH(R5)-,
(vii) -C(R5')(R5)-CH(R5)-,
(viii) -CH(R5)-C(R5,)(R5)-,
(ix) -CH(R5)-N(R5)-,
(x) -CH(R5)-O-,
(xi) -CH(R5)-S-,
(xii) -N(R5)-N(R5)-,
(xiii) -C(R5)=C(R5)- or
(xiv) -CH(R5)-C(R5')(R5)-N(R5)- wherein at each occurrence R5 is independently selected from hydrogen, loweralkyl, alkoxy-substituted loweralkyl, halo-substituted loweralkyl, carboxy-substituted loweralkyl, heterocyclic-substituted loweralkyl, alkenyl, alkynyl, cycloalkyl or cycloalkylalkyl and R5' is hydrogen, halo, hydroxy, carboxy, alkoxy or thioalkoxy;

and M' are independently selected from
(i) hydrogen,
(ii) loweralkyl,
(iii) halo-substituted loweralkyl,
(iv) halo,
(v) -CN,
(vi) -NO2,
(vii) -OH,
(viii) hydroxy-substituted loweralkyl,
(ix) alkoxy-substituted loweralkyl,
(x) -NH2,
(xi) alkylamino,
(xii) dialkylamino,
(xiii) -SH, (xiv) alkoxy and
(xv) thioalkoxy;

R1' are independently selected from
(i) tetrazolyl,

or
,


,
(iv) -NH-C(=N(R50a))(R51a) wherein R50a is hydrogen, -CN or -NO2 and R51a is hydrogen, loweralkyl, alkylamino, dialkylamino, alkoxy or thioalkoxy,
(v) -NH(R51b) wherein R51b is a 5-membered aromatic heterocyclic
ring wherein the heterocyclic ring contains 1 , 2, 3 or 4 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 2 nitrogen atoms and 1 oxygen atom or 1 oxygen atom and 1 sulfur atom and wherein the 5- membered heterocyclic ring is unsubstituted or susbstituted with a substituted selected from amino, alkylamino, dialkylamino, hydroxy, alkoxy, thioalkoxy, halo, loweralkyl and halo-substituted loweralkyl,

(vi) -COOR6 or -CH2COOR6 wherein R6 is hydrogen or a carboxy- protecting group or
(vii) -NHS(O)2R7 or -CH2NHS(O)2R7 or -NHC(O)R7a or -CH2NHC(O)R7a wherein R7 is loweralkyl, halo-substituted
loweralkyl or -NR7bR7c wherein R7b and R7c are independently
selected from hydrogen and loweralkyl and R7a is loweralkyl, halo- substituted loweralkyl, amino, alkylamino, dialkylamino or -COOH;
(viii) -C(O)NR50R51 or -CH2C(0)NRδθR51 or -NHC(O)NR50R51
or -CH2NHC(O)NR50R51 or-NHC(S)NR50R51 or
-CH2NHC(S)NR50R51 wherein R50 and R51 are independently
selected from hydrogen, loweralkyl, hydroxy, alkoxy, hydroxysubstituted loweralkyl, alkoxy-substituted loweralkyl, alkoxysubstituted alkoxy and -S(O)2R50a wherein R50a is loweralkyl or
aryl, or R50 and R51 taken together with the nitrogen atom to which
they are attached form a 5- to 7-membered aliphatic heterocycle;
(ix) -CH2OR52 wherein R52 is selected from hydrogen, loweralkyl and
-C(O)R53 wherein R53 is hydrogen, loweralkyl or aryl;
(x) -CH(OH)R52a or-C(O)R52a wherein R52a is loweralkyl, halo- substituted loweralkyl, -CF2COOR53a or -CH2COOR53a
wherein R53a is hydrogen or a carboxy-protecting group,
(xii) -CH2NR54R55 wherein R54 is selected from hydrogen, loweralkyl, -C(O)R56, -C(O)NR56R57 and -S(O)2R58 wherein R56 is selected
from hydrogen, loweralkyl and aryl and R58 is selected from lower
alkyl and halo-substituted loweralkyl and wherein R55 and R57 are
independently selected from hydrogen, loweralkyl, hydroxy and
alkoxy;
(xiii) -SO3H, -OSO3H or -CH2SO3H,
(xiv) -OPO3H2, -PO3H2 or -CH2PO3H2,
(xv) -SO2NR50R51 or -CH2SO2NR50R51 wherein R50 and R51
are defined as above and
(xvi) -C(O)NHSO2R60, -C(O)NHC(O)R60 or -C(O)NHNHSO2R60 wherein R60 is ioweralkyl, halo-substituted loweralkyl or aryl;
with the proviso that one of R1 and R1' is hydrogen, but R 1 and R1' are not both hydrogen;
and D is
(i) a bicyclic heterocycle comprising a 6-membered ring fused to a
5-membered ring, the bicyclic heterocycle comprising at least one
heteroatom selected from N, O and S; the 6-membered ring of the bicyclic heterocycle comprising 0, 1, 2 or 3 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 1 nitrogen atom and 1 sulfur atom or 1 oxygen atom and 1 sulfur atom or 2 oxygen atoms or 2 sulfur atoms or 1 oxygen atom or 1 sulfur atom, the remaining ring atoms being carbon atoms and the 6-membered ring comprising 0, 1 , 2 or 3 double bonds; the 5-membered ring of the bicyclic heterocycle comprising 0, 1 , 2 or 3 nitrogen atoms or 1 nitrogen and 1 oxygen atom or 1 nitrogen and 1 sulfur atom or 1 oxygen atom and 1 sulfur atom or 1 sulfur atom or 1 oxygen atom, the remaining ring atoms being carbon atoms and the 5-membered ring comprising 0, 1 or 2 double bonds; the nitrogen atoms of the bicyclic heterocycle can be substituted with a substituent R2 wherein at each occurrence R2 is independently selected from hydrogen, ioweralkyl, carboxy-substituted loweralkyl or alkoxycarbonyl-substituted loweralkyl; the nitrogen atoms of the bicyclic heterocycle can be oxidized; one or two carbon atoms of the bicyclic heterocycle can be substituted with an oxo (=O) substituent and the sulfur atoms of the bicyclic heterocycle can be substituted with one or two oxo (=O) substituents; the bicyclic heterocycle can be substituted with one, two or three substituents independently selected from R3 and R4, R3 being bonded to a carbon atom or a nitrogen atom of the bicyclic heterocycle and R4 being bonded to a carbon atom or a nitrogen atom of the bicyclic heterocycle, wherein

R3 is
(i) hydrogen,
(ii) loweralkyl,
(iii) halo,
(iv) halo-substituted loweralkyl,
(v) thioalkoxy, (vi) alkoxy-substituted loweralkyl,
(vii) thioalkoxy-substituted ioweralkyl,
(viii) aryl,
(ix) arylalkyl,
(x) -NO2,
(xi) -COOR8 wherein R8 is hydrogen or a carboxy-protecting group,

(xii) -OR9 wherein R9 is hydrogen, ioweralkyl, halo-substituted loweralkyl, aryl, arylalkyl, heterocyclic-substituted loweralkyl or -C(O)R10 wherein R10 is ioweralkyl, halo- substituted loweralkyl, -PO3H2 or -NR11R12 wherein R11 and R12 are independently selected from hydrogen and loweralkyl and
(xiii) -NR13R14 or -CH2NR13R14 wherein R13 and R14 are
independently selected from (1 ) hydrogen, (2) lower
alkyl, (3) arylalkyl, (4) -C(O)R15, (5) -S(O)2R15 wherein R15 is loweralkyl or halo- substituted loweralkyl and
(6) -R16-R17 wherein R16 is alkylene and R17 is
(a) -NR18R19 wherein R18 and R19 are independently
selected from hydrogen and loweralkyl or
(b) unsubstituted or loweralkyl substituted aziridinyl,
azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl,
morpholinyl, thiomorpholinyl, pyridinyl or pyrimidinyl,
or R13 and R14 taken together with the nitrogen atom to
which they are attached form a 5- to 7-membered aliphatic
heterocycle and

(i) hydrogen,
(ii) loweralkyl,
(iii) halo-substituted loweralkyl,
(iv) -CN,
(v) -NO2.
(vi) -NH2, (vii) -NH-C(=N(R25a))(R26a) wherein R25a is hydrogen, -CN or -NO2 and R26a is hydrogen, loweralkyl, alkylamino, dialkylamino, alkoxy or thioalkoxy,
(viii) -NH(R26b) wherein R26b is a 5-membered aromatic heterocyclic ring wherein the heterocyclic ring contains 1 , 2, 3 or 4 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 2 nitrogen atoms and 1 oxygen atom or 1 oxygen atom and 1 sulfur atom and wherein the 5- membered heterocyclic ring is unsubstituted or susbstituted with a substitutent selected from amino, alkylamino, dialkylamino, hydroxy, alkoxy, thioalkoxy, halo, loweralkyl and halo-substituted loweralkyl, (ix) -CHO or-CH(=N-OH),
(x) tetrazolyl.
(xi) -NHS(O)2R20 or -CH2NHS(O)2R20 or -NHC(O)R21 or
-N(OH)C(O)R21 or -CH2NHC(O)R21 or -CH2N(OH)C(O)R21 wherein R20 is loweralkyl, halo- substituted loweralkyl or -NR27aR27b wherein R27a and R27b are independently selected from hydrogen, -OH and loweralkyl and R21 is loweralkyl, halo-substituted ioweralkyl, amino, alkylamino, dialkylamino or -COOH,
(xii) -CH(OH)R22 or -C(O)R22 wherein R22 is loweralkyl, halo- substituted loweralkyl, -CF2COOR23 or -CH2COOR23
wherein R23 is hydrogen or a carboxy-protecting group,
(xiii) -COOR24 or -CH2COOR24 wherein R24 is hydrogen or a carboxy-protecting group,
(xiv) -C(O)NR25R26 or -CH2C(O)NR25R26 or -NHC(O)NR25R26 or -CH2NHC(O)NR25R26 or-NHC(S)NR25R26
or -CH2NHC(S)NR25R26 wherein R25 and R26 are
independently selected from hydrogen, loweralkyl,
hydroxy, alkoxy, hydroxy-substituted loweralkyl,
alkoxy-substituted loweralkyl, alkoxy-substituted
alkoxy and -S(O)2R28a wherein R28a is loweralkyl or aryl, or R25 and R26 taken together with the nitrogen atom to which they are attached form a 5- to 7- membered aliphatic heterocycle;

(xv) -CH2OR27 wherein R27 is selected from hydrogen,
loweralkyl and -C(O)R28 wherein R28 is hydrogen,
loweralkyl or aryl;
(xvi) -CH2NR29R30 wherein R29 is selected from hydrogen,
ioweralkyl, -C(O)R31 , -C(O)NR31 R32 and -S(O)2R33
wherein R31 is selected from hydrogen, loweralkyl and
aryl and R33 is selected from loweralkyl and halo- substituted loweralkyl and wherein R30 and R32 are
independently selected from hydrogen, loweralkyl,
hydroxy and alkoxy;
(xvii) -SO3H, -OSO3H or-CH2SO3H,
(xviii) -OPO3H, -PO3H2 or -CH2PO3H2,
(xix) -SO2NR25R26 or -CH2SO2NR25R26 wherein R25 and R26
are defined as above and
(xx) -C(O)NHSO2R59, -C(O)NHC(O)R59 or -C(O)NHNHSO2R59
wherein R59 is loweralkyl, halo-substituted loweralkyl or
aryl;
or D is

(ii) a bicyclic heterocycle comprising a 5-membered ring fused to a
5-membered ring, the bicyclic heterocycle comprising at least one
heteroatom selected from N, O and S; each of the 5-membered rings of the bicyclic heterocycle independently comprising 0, 1 , 2 or 3 nitrogen atoms or 1 nitrogen and 1 oxygen atom or 1 nitrogen and 1 sulfur atom or 1 oxygen atom and 1 sulfur atom or 1 sulfur atom or 1 oxygen atom, the remaining ring atoms being carbon atoms and each of the 5-membered rings
independently comprising 0, 1 or 2 double bonds; the nitrogen atoms of the bicyclic heterocycle can be substituted with a substituent R2 wherein at each occurrence R2 is independently selected from hydrogen, loweralkyl, carboxy-substituted loweralkyl or alkoxycarbonyl-substituted loweralkyl; the nitrogen atoms of the bicyclic heterocycle can be oxidized; one or two carbon atoms of the bicyclic heterocycle can be substituted with an oxo (=O) substituent and the sulfur atoms of the bicyclic heterocycle can be
substituted with one or two oxo (=O) substituents; the bicyclic heterocycle can be substituted with one or two substituents independently selected from R3 and R4, R3 being bonded to a carbon atom or a nitrogen atom of the bicyclic heterocycle and R4 being bonded to a carbon atom or a nitrogen atom of the bicyclic heterocycle, wherein R3 and R4 are defined as above;

or D is

or


wherein R3 and R4 are defined as above;
or a pharmaceutically acceptable salt or prodrug thereof.

2. The compound of Claim 1 wherein A is a covalent bond, L, L', M, M' and R 1' are hydrogen, -G-E- is -CH2-N(R5)- and D is a substituted purinyl group.

3. A compound of the formula:



wherein

A is
(i) a covalent bond,
(ii) -O-,
(iii) -C(O)-,
(iv) -CH2-,
(v) -S-, -S(O)- or -S(O)2-;

E-G is
(i) -N(R5)-,
(ii) -O-,
(iii) -S-,
(iv) -N(R5)-CH(R5)-,
(v) -O-CH(R5)-,
(vi) -S-CH(R5)-,
(vii) -C(R5')(R5)-CH(R5)-, (viii) -CH(R5)-C(R5')(R5)-,
(ix) -CH(R5)-N(R5)-,
(x) -CH(R5)-O-,
(xi) -CH(R5)-S-,
(xii) -N(R5)-N(R5)-,
(xiii) -C(R5)=C(R5)- or
(xiv) -CH(R5)-C(R5')(R5)-N(R5)- wherein at each occurrence R5 is
independently selected from hydrogen, loweralkyl, alkoxy-substituted loweralkyl, halo-substituted loweralkyl, carboxy-substituted loweralkyl, heterocyclic-substituted loweralkyl, alkenyl, alkynyl, cycloalkyl or
cycloalkyialkyi and R5' is hydrogen, halo, hydroxy, carboxy, alkoxy or thioalkoxy;

L, L', M and M' are independently selected from
(i) hydrogen,
(ii) loweralkyl,
(iii) halo-substituted loweralkyl,
(iv) halo,
(v) -CN,
(vi) -NO2,
(vii) -OH,
(viii) hydroxy-substituted loweralkyl,
(ix) alkoxy-substituted loweralkyl,
(x) -NH2,
(xi) alkylamino,
(xii) dialkylamino,
(xiii) -SH,
(xiv) alkoxy and
(xv) thioalkoxy;

R1 and R1 ' are independently selected from
(i) tetrazolyl, or
,



,
(iv) -NH-C(=N(R50a))(R51a) wherein R50a is hydrogen, -CN or -NO2 and R51a is hydrogen, loweralkyl, alkylamino, dialkylamino, alkoxy or thioalkoxy,
(v) -NH(R51b) wherein R51b is a 5-membered aromatic heterocyclic
ring wherein the heterocyclic ring contains 1 , 2, 3 or 4 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 2 nitrogen atoms,and 1
oxygen atom or 1 oxygen atom and 1 sulfur atom and wherein the 5- membered heterocyclic ring is unsubstituted or susbstituted with a substitutent selected from amino, alkylamino, dialkylamino, hydroxy, alkoxy, thioalkoxy, halo, loweralkyl and halo-substituted ioweralkyl,

(vi) -COOR6 or -CH2COOR6 wherein R6 is hydrogen or a carboxy- protecting group or
(vii) -NHS(O)2R7 or -CH2NHS(O)2R7 or -NHC(O)R7a or
-CH2NHC(O)R7a wherein R7 is loweralkyl, halo-substituted
loweralkyl or -NR7bR7c wherein R7b and R7C are independently
selected from hydrogen and loweralkyl and R7a is loweralkyl, halo- substituted loweralkyl, amino, alkylamino, dialkylamino or -COOH;

(viii) -C(O)NR50R51 or -CH2C(O)NR50R51 or -NHC(O)NR50R51 or -CH2NHC(O)NR50R51 or -NHC(S)NR50R51 or
-CH2NHC(S)NR50R51 wherein R50 and R51 are independently
selected from hydrogen, loweralkyl, hydroxy, alkoxy, hydroxy- substituted loweralkyl, alkoxy-substituted loweralkyl, alkoxy- substituted alkoxy and -S(O)2R50a wherein R50a is loweralkyl or
aryl, or R50 and R51 taken together with the nitrogen atom to which
they are attached form a 5- to 7-membered aliphatic heterocycle;
(ix) -CH2OR52 wherein R52 is selected from hydrogen, loweralkyl and
-C(O)R53 wherein R53 is hydrogen, loweralkyl or aryl;
(x) -CH(OH)R52a or -C(O)R52a wherein R52a is loweralkyl, halo- substituted loweralkyl, -CF2COOR53a or -CH2COOR53a
wherein R53a is hydrogen or a carboxy-protecting group,
(xii) -CH2NR54R55 wherein R54 is selected from hydrogen, loweralkyl, -C(O)R56, -C(O)NR56R57 and -S(O)2R58 wherein R56 is selected
from hydrogen, loweralkyl and aryl and R58 is selected from lower
alkyl and halo-substituted loweralkyl and wherein R55 and R57 are
independently selected from hydrogen, loweralkyl, hydroxy and
alkoxy;
(xiii) -SO3H, -OSO3H or -CH2SO3H,
(xiv) -OPO3H2, -PO3H2 or -CH2PO3H2,
(xv) -SO2NR50R51 or -CH2SO2NR50R51 wherein R50 and R51
are defined as above and
(xvi) -C(O)NHSO2R60, -C(O)NHC(O)R60 or -C(O)NHNHSO2R60 wherein R60 is loweralkyl, halo-substituted loweralkyl or aryl;
with the proviso that one of R1 and R1' is hydrogen, but R1 and R1' are not both hydrogen;
and

D is
(i) a bicyclic heterocycle comprising a 6-membered ring fused to a
5-membered ring, the bicyclic heterocycle comprising at least one
heteroatom selected from N, O and S; the 6-membered ring of the bicyclic heterocycle comprising 0, 1 , 2 or 3 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 1 nitrogen atom and 1 sulfur atom or 1 oxygen atom and 1 sulfur atom or 2 oxygen atoms or 2 sulfur atoms or 1 oxygen atom or 1 sulfur atom, the remaining ring atoms being carbon atoms and the 6-membered ring comprising 0, 1 , 2 or 3 double bonds; the 5-membered ring of the bicyclic heterocycle comprising 0, 1 , 2 or 3 nitrogen atoms or 1 nitrogen and 1 oxygen atom or 1 nitrogen and 1 sulfur atom or 1 oxygen atom and 1 sulfur atom or 1 sulfur atom or 1 oxygen atom, the remaining ring atoms being carbon atoms and the 5-membered ring comprising 0, 1 or 2 double bonds; the nitrogen atoms of the bicyclic heterocycle can be substituted with a substituent R2 wherein at each occurrence R2 is independently selected from hydrogen, loweralkyl, carboxy-substituted loweralkyl or alkoxycarbonyl-substituted loweralkyl; the nitrogen atoms of the bicyclic heterocycle can be oxidized; one or two carbon atoms of the bicyclic heterocycle can be substituted with an oxo (=O) substituent and the sulfur atoms of the bicyclic heterocycle can be substituted with one or two oxo (=O) substituents; the bicyclic heterocycle can be substituted with one, two or three substituents independently selected from R3 and R4, R3 being bonded to a carbon atom or a nitrogen atom of the bicyclic heterocycle and R4 being bonded to a carbon atom or a nitrogen atom of the bicyclic heterocycle, wherein

R3 is
(i) hydrogen,
(ii) loweralkyl,
(iii) halo,
(iv) halo-substituted loweralkyl,
(v) thioalkoxy,
(vi) alkoxy-substituted loweralkyl,
(vii) thioalkoxy-substituted loweralkyl,
(viii) aryl,
(ix) arylalkyl,
(x) -NO2, (xi) -COOR8 wherein R8 is hydrogen or a carboxy-protecting group, (xii) -OR9 wherein R9 is hydrogen, loweralkyl, halo-substituted
Ioweralkyl, aryl, arylalkyl, heterocyclic-substituted ioweralkyl or
-C(O)R10 wherein R10 is loweralkyl, halo- substituted loweralkyl, -PO3H2 or -NR11R12 wherein R11 and R12 are independently selected from hydrogen and loweralkyl and
(xiii) -NR13R14 or -CH2NR13R14 wherein R13 and R14 are
independently selected from (1 ) hydrogen, (2) lower
alkyl, (3) arylalkyl, (4) -C(O)R15, (5) -S(O)2R15 wherein R15 is
loweralkyl or halo- substituted loweralkyl and
(6) -R16-R17 wherein R16 is alkylene and R17 is
(a) -NR18R19 wherein R18 and R19 are independently
selected from hydrogen and ioweralkyl or
(b) unsubstituted or loweralkyl substituted aziridinyl,
azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl,
morphoiinyl, thiomorpholinyl, pyridinyl or pyrimidinyl,
or R13 and R14 taken together with the nitrogen atom to
which they are attached form a 5- to 7-membered aliphatic
heterocycle and

(i) hydrogen,
(ii) loweralkyl,
(iii) halo-substituted loweralkyl,
(iv) -CN,
(v) -NO2,
(vi) -NH2,
(vii) -NH-C(=N(R25a))(R26a) wherein R25a is hydrogen, -CN or-NO2 and

R26a is hydrogen, loweralkyl, alkylamino, dialkylamino, alkoxy or thioalkoxy,
(viii) -NH(R26b) wherein R26b is a 5-membered aromatic heterocyclic ring wherein the heterocyclic ring contains 1 , 2, 3 or 4 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 2 nitrogen atoms and 1 oxygen atom or 1 oxygen atom and 1 sulfur atom and wherein the 5- membered heterocyclic ring is unsubstituted or susbstituted with a substitutent selected from amino, alkylamino, dialkylamino, hydroxy, alkoxy, thioalkoxy, halo, loweralkyl and halo-substituted loweralkyl, (ix) -CHO or -CH(=N-OH),
(x) tetrazolyl,
(xi) -NHS(O)2R20 or -CH2NHS(O)2R20 or -NHC(O)R21 or
-N(OH)C(O)R21 or-CH2NHC(O)R21 or -CH2N(OH)C(O)R21 wherein R20 is ioweralkyl, halo- substituted loweralkyl or -NR27aR27b wherein R27a and R27b are independently selected from hydrogen, -OH and loweralkyl and R21 is loweralkyl, halo-substituted loweralkyl, amino, alkylamino, dialkylamino or -COOH,
(xii) -CH(OH)R22 or -C(O)R22 wherein R22 is loweralkyl, halo- substituted loweralkyl, -CF2COOR23 or -CH2COOR23
wherein R23 is hydrogen or a carboxy-protecting group,
(xiii) -COOR24 or -CH2COOR24 wherein R24 is hydrogen or a carboxy-protecting group,
(xiv) -C(O)NR25R26 or -CH2C(O)NR25R26 or-NHC(O)NR25R26 or -CH2NHC(O)NR25R26 or -NHC(S)NR25R26
or -CH2NHC(S)NR25R26 wherein R25 and R26 are
independently selected from hydrogen, loweralkyl,
hydroxy, alkoxy, hydroxy-substituted loweralkyl,
alkoxy-substituted loweralkyl, alkoxy-substituted
alkoxy and -S(O)2R28a wherein R28a is loweralkyl or aryl, or R25 and R26 taken together with the nitrogen atom to which they are attached form a 5- to 7- membered aliphatic heterocycle;
(xv) -CH2OR27 wherein R27 is selected from hydrogen,
loweralkyl and -C(O)R28 wherein R28 is hydrogen,
loweralkyl or aryl;
(xvi) -CH2NR29R30 wherein R29 is selected from hydrogen,
loweralkyl, -C(O)R31 , -C(O)NR31 R32 and -S(O)2R33 wherein R31 is selected from hydrogen, ioweralkyl and
aryl and R33 is selected from ioweralkyl and halo- substituted loweralkyl and wherein R30 and R32 are
independently selected from hydrogen, loweralkyl,
hydroxy and alkoxy;
(xvii) -SO3H, -OSO3H or -CH2SO3H,
(xviii) -OPO3H, -PO3H2 or -CH2PO3H2.
(xix) -SO2NR25R26 or -CH2SO2NR25R26 wherein R25 and R26
are defined as above and
(xx) -C(O)NHSO2R59, -C(O)NHC(O)R59 or -C(O)NHNHSO2R59
wherein R59 is loweralkyl, halo-substituted loweralkyl or
aryl;
or D is

or


wherein R3 and R4 are defined as above;
or a pharmaceutically acceptable salt or prodrug thereof.

4. The compound of Claim 3 wherein A is a covalent bond, L, L', M, M' and R1' are hydrogen, -G-E- is -CH2-N(R5)- and D is a substituted purinyl group.

5. A compound of the formula:



wherein

A is
(i) a covalent bond,
(ii) -O-,
(iii) -C(O)-,
(iv) -CH2-.
(v) -S-, -S(O)- or -S(O)2-;

E-G is
(i) -N(R5)-,
(ii) -O-,
(iii) -S-,
(iv) -N(R5)-CH(R5)-,
(v) -O-CH(R5)-,
(vi) -S-CH(R5)-, (vii) -C(R5')(R5)-CH(R5)-,
(viii) -CH(R5)-C(R5')(R5)-,
(ix) -CH(R5)-N(R5)-,
(x) -CH(R5)-O-,
(xi) -CH(R5)-S-,
(xii) -N(R5)-N(R5)-,
(xiii) -C(R5)=C(R5)- or
(xiv) -CH(R5)-C(R5')(R5)-N(R5)- wherein at each occurrence R5 is independently selected from hydrogen, loweralkyl, alkoxy-substituted loweralkyl, halo-substituted loweralkyl, carboxy-substituted loweralkyl, heterocyclic-substituted loweralkyl, alkenyl, alkynyl, cycloalkyl or cycloalkylalkyl and R5' is hydrogen, halo, hydroxy, carboxy, alkoxy or thioalkoxy;

and M' are independently selected from
(i) hydrogen,
(ii) loweralkyl.
(iii) halo-substituted loweralkyl,
(iv) halo,
(v) -CN,
(vi) -NO2,
(vii) -OH,
(viii) hydroxy-substituted loweralkyl,
(ix) alkoxy-substituted loweralkyl,
(x) -NH2,
(xi) alkylamino,
(xii) dialkylamino,
(xiii) -SH,
(xiv) alkoxy and
(xv) thioalkoxy;

R1' are independently selected from (i) tetrazolyl,


or
,

,


(iv) -NH-C(=N(R50a))(R51a) wherein R50a is hydrogen, -CN or -NO2 and R51a is hydrogen, loweralkyl, alkylamino, dialkylamino, alkoxy or thioalkoxy,
(v) -NH(R51b) wherein R51b is a 5-membered aromatic heterocyclic
ring wherein the heterocyclic ring contains 1 , 2, 3 or 4 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 2 nitrogen atoms and 1
oxygen atom or 1 oxygen atom and 1 sulfur atom and wherein the 5- membered heterocyclic ring is unsubstituted or susbstituted with a substituted selected from amino, alkylamino, dialkylamino, hydroxy, alkoxy, thioalkoxy, halo, loweralkyl and halo-substituted loweralkyl,

(vi) -COOR6 or -CH2COOR6 wherein R6 is hydrogen or a carboxy- protecting group or
(vii) -NHS(O)2R7 or -CH2NHS(O)2R7 or -NHC(O)R7a or
-CH2NHC(O)R7a wherein R7 is loweralkyl, halo-substituted
loweralkyl or -NR7bR7c wherein R7b and R7c are independently
selected from hydrogen and loweralkyl and R7a is loweralkyl, halo- substituted loweralkyl, amino, alkylamino, dialkylamino or -COOH;

(viii) -C(O)NR50R51 or -CH2C(O)NR50R51 or -NHC(O)NR50R51
or -CH2NHC(O)NR50R51 or -NHC(S)NR50R51 or
-CH2NHC(S)NR50R51 wherein R50 and R51 are independently
selected from hydrogen, loweralkyl, hydroxy, alkoxy, hydroxy- substituted loweralkyl, alkoxy-substituted ioweralkyl, alkoxysubstituted alkoxy and -S(O)2R50a wherein R50a is loweralkyl or
aryl, or R50 and R51 taken together with the nitrogen atom to which
they are attached form a 5- to 7-membered aliphatic heterocycle;
(ix) -CH2OR52 wherein R52 is selected from hydrogen, loweralkyl and
-C(O)R53 wherein R53 is hydrogen, loweralkyl or aryl;
(x) -CH(OH)R52a or -C(O)R52a wherein R52a is loweralkyl, halo- substituted loweralkyl, -CF2COOR53a or -CH2COOR53a
wherein R53a is hydrogen or a carboxy-protecting group,
(xii) -CH2NR54R55 wherein R54 is selected from hydrogen, loweralkyl, -C(O)R56, -C(O)NR56R57 and -S(O)2R58 wherein R56 is selected
from hydrogen, loweralkyl and aryl and R58 is selected from lower
alkyl and halo-substituted loweralkyl and wherein R55 and R57 are
independently selected from hydrogen, loweralkyl, hydroxy and
alkoxy;
(xiii) -SO3H, -OSO3H or -CH2SO3H,
(xiv) -OPO3H2, -PO3H2 or-CH2PO3H2,
(xv) -SO2NR50R51 or -CH2SO2NR50R51 wherein R50 and R51
are defined as above and
(xvi) -C(O)NHSO2R60, -C(O)NHC(O)R60 or -C(O)NHNHSO2R60 wherein R60 is loweralkyl, halo-substituted loweralkyl or aryl;
with the proviso that one of R1 and R1' is hydrogen, but R1 and R1 ' are not both hydrogen;
and

D is


wherein R2 is selected from hydrogen, loweralkyl, carboxy-substituted loweralkyl or alkoxycarbonyl-substituted loweralkyl,
R3 is
(i) hydrogen,
(ii) loweralkyl,
(iii) halo,
(iv) halo-substituted loweralkyl,
(v) thioalkoxy,
(vi) alkoxy-substituted loweralkyl,
(vii) thioalkoxy-substituted loweralkyl,
(viii) aryl,
(ix) arylalkyl,
(x) -NO2,
(xi) -COOR8 wherein R8 is hydrogen or a carboxy-protecting group,
(xii) -OR9 wherein R9 is hydrogen, loweralkyl, halo-substituted
loweralkyl, aryl, arylalkyl, heterocyclic-substituted loweralkyl or
-C(O)R10 wherein R10 is loweralkyl, halo- substituted ioweralkyl,
-PO3H2 or -NR11R12 wherein R11 and R12 are independently selected from hydrogen and loweralkyl and (xiii) -NR13R14 or -CH2NR13R14 wherein R13 and R14 are
independently selected from (1) hydrogen, (2) lower
alkyl, (3) arylalkyl, (4) -C(O)R15, (5) -S(O)2R15 wherein R15 is
ioweralkyl or halo- substituted ioweralkyl and
(6) -R16-R17 wherein R16 is alkylene and R17 is
(a) -NR18R19 wherein R18 and R19 are independently
selected from hydrogen and loweralkyl or
(b) unsubstituted or loweralkyl substituted aziridinyl,
azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl,
morpholinyl, thiomorpholinyl, pyridinyl or pyrimidinyl,
or R13 and R14 taken together with the nitrogen atom to
which they are attached form a 5- to 7-membered aliphatic
heterocycle and

R4 is
(i) hydrogen,
(ii) loweralkyl,
(iii) halo-substituted loweralkyl,
(iv) -CN,
(v) -NO2.
(vi) -NH2,
(vii) -NH-C(=N(R25a))(R26a) wherein R25a is hydrogen, -CN or -NO2 and R26a is hydrogen, loweralkyl, alkylamino, dialkylamino, alkoxy or
thioalkoxy,
(viii) -NH(R26b) wherein R26b is a 5-membered aromatic heterocyclic
ring wherein the heterocyclic ring contains 1 , 2, 3 or 4 nitrogen atoms or 1 nitrogen atom and 1 oxygen atom or 2 nitrogen atoms and 1
oxygen atom or 1 oxygen atom and 1 sulfur atom and wherein the 5- membered heterocyclic ring is unsubstituted or susbstituted with a
substitutent selected from amino, alkylamino, dialkylamino, hydroxy, alkoxy, thioalkoxy, halo, loweralkyl and halo-substituted loweralkyl,

(ix) -CHO or-CH(=N-OH), (x) tetrazolyl,
(xi) -NHS(O)2R20 or -CH2NHS(O)2R20 or -NHC(O)R21 or
-N(OH)C(O)R21 or -CH2NHC(O)R21 or -CH2N(OH)C(O)R21 wherein R20 is loweralkyl, halo- substituted loweralkyl or -NR27aR27b wherein R27a and R27b are independently selected from hydrogen, -OH and loweralkyl and R21 is loweralkyl, halo-substituted loweralkyl, amino, alkylamino, dialkylamino or -COOH,
(xii) -CH(OH)R22 or -C(O)R22 wherein R22 is loweralkyl, halo- substituted loweralkyl, -CF2COOR23 or -CH2COOR23
wherein R23 is hydrogen or a carboxy-protecting group,
(xiii) -COOR24 or -CH2COOR24 wherein R24 is hydrogen or a carboxy-protecting group,
(xiv) -C(O)NR25R26 or -CH2C(O)NR25R26 or -NHC(O)NR25R26 or -CH2NHC(O)NR25R26 or-NHC(S)NR25R26
or -CH2NHC(S)NR25R26 wherein R25 and R26 are
independently selected from hydrogen, loweralkyl,
hydroxy, alkoxy, hydroxy-substituted loweralkyl,
alkoxy-substituted loweralkyl, alkoxy-substituted
alkoxy and -S(O)2R28a wherein R28a is loweralkyl or aryl, or R25 and R26 taken together with the nitrogen atom to which they are attached form a 5- to 7- membered aliphatic heterocycle;
(xv) -CH2OR27 wherein R27 is selected from hydrogen,
loweralkyl and -C(O)R28 wherein R28 is hydrogen,
loweralkyl or aryl;
(xvi) -CH2NR29R30 wherein R29 is selected from hydrogen, loweralkyl, -C(O)R31 , -C(O)NR31 R32 and -S(O)2R33
wherein R31 is selected from hydrogen, loweralkyl and
aryl and R33 is selected from loweralkyl and halosubstituted loweralkyl and wherein R30 and R32 are
independently selected from hydrogen, loweralkyl,
hydroxy and alkoxy;
(xvii) -SO3H, -OSO3H or -CH2SO3H, (xviii) -OPO3H, -PO3H2 or -CH2PO3H2,
(xix) -SO2NR25R26 or -CH2SO2NR25R26 wherein R25 and R26
are defined as above and
(xx) -C(O)NHSO2R59, -C(O)NHC(O)R59 or -C(O)NHNHSO2R59
wherein R59 is loweralkyl, halo-substituted loweralkyl or
aryl;
or a pharmaceutically acceptable salt or prodrug thereof.

6. The compound of Claim 5 wherein A is a covalent bond, L, L', M, M' and R1' are hydrogen and -G-E- is -CH2-N(R5)-.

7. A pharmaceutical composition for blocking the interaction of angiotensin II with angiotensin II receptors comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Claim 1.

8. A pharmaceutical composition for treating hypertension or
congestive heart failure comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Claim 1.

9. A method of blocking the interaction of angiotensin II with angiotensin II receptors comprising administering to a human or other mammal in need a therapeutically effective amount of a compound of Claim 1.

10. A method of treating hypertension or heart failure comprising administering to a human or other mammal in need a therapeutically effective amount of a compound of Claim 1.