US 5,312,820 AGranted

Substituted carbamoyl and oxycarbonyl derivatives of biphenylmethylamines

AssigneeMerck & Co., Inc.

InventorsWallace T. Ashton, Linda L. Chang, William J. Greenlee, Steven M. Hutchins, Ralph A. Rivero

Life of this patent

Estimating the term…

Abstract

Carbamoyl and oxycarbonyl derivatives of biphenylmethylamines of structure I are angiotensin-II antagonists with balanced AT.sub.1 and AT.sub.2 activity useful in the treatment of hypertension and related disorders and ocular hypertension. ##STR1## where X is --O-- or --N(R.sup.7)--.

Claims22

Dependent claims

A compound of structural formula:

##STR33## or a pharmaceutically acceptable salt thereof wherein:
A, B, C, and D are independently --CH.dbd. or --N.dbd., with the proviso that at least two of them are --CH.dbd.;
X is --O-- or --N(R.sup.7)--;
R.sup.1 is
(a) --CO.sub.2 R.sup.4,
(b) --SO.sub.3 R.sup.5,
(c) --NHSO.sub.2 CF.sub.3,
(d) --PO(OR.sup.5).sub.2,
(e) --SO.sub.2 --NH--R.sup.9,
(f) --CONHOR.sup.5,
(g) --SO.sub.2 NH-heteroaryl,
(h) --CH.sub.2 SO.sub.2 NH-heteroaryl,
(i) --SO.sub.2 NHCOR.sup.23,
(j) --CH.sub.2 SO.sub.2 NHCOR.sup.23,
(k) --CONHSO.sub.2 R.sup.23,
(l) --CH.sub.2 CONHSO.sub.2 R.sup.23,
(m) --NHSO.sub.2 NHCOR.sup.23,
(n) --NHCONHSO.sub.2 R.sup.23,
(o) --SO.sub.2 NHSO.sub.2 R.sup.23,
(p) --SO.sub.2 NHCO.sub.2 R.sup.20,
(q) --SO.sub.2 NHCONHR.sup.20, ##STR34## wherein:
Y is
(1) --CO.sub.2 R.sup.4,
(2) --SO.sub.3 R.sup.5,
(3) --NHSO.sub.2 CF.sub.3,
(4) --PO(OR.sup.5).sub.2, or
(5) --SO.sub.2 --NH--R.sup.9 ;
(6) 1H-tetrazol-5-yl;
R.sup.2a and R.sup.2b are each independently:
(a) hydrogen,
(b) halo,
(c) --NO.sub.2,
(d) --NH.sub.2,
(e) C.sub.1 -C.sub.4 -alkylamino,
(f) --SO.sub.2 NHR.sup.9,
(g) --CF.sub.3,
(h) C.sub.1 -C.sub.4 -alkyl
(i) C.sub.1 -C.sub.4 -alkoxy;
R.sup.3a is
(a) --H,
(b) halo,
(c) C.sub.1 -C.sub.6 -alkyl,
(d) C.sub.1 -C.sub.6 -alkoxy,
(e) C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.4 -alkyl;
R.sup.3b is
(a) --H,
(b) --halo,
(c) --NO.sub.2,
(d) C.sub.1 -C.sub.6 -alkyl,
(e) C.sub.1 -C.sub.5 -alkylcarbonyloxy,
(f) C.sub.3 -C.sub.6 -cycloalkyl
(g) C.sub.1 -C.sub.6 -alkoxy,
(h) --NHSO.sub.2 R.sup.4,
(i) hydroxy-C.sub.1 -C.sub.4 -alkyl,
(j) aryl-C.sub.1 -C.sub.4 -alkyl
(k) C.sub.1 -C.sub.4 -alkylthio
(l) C.sub.1 -C.sub.4 -alkylsulfinyl
(m) C.sub.1 -C.sub.4 -alkylsulfonyl
(n) --NH.sub.2
(o) C.sub.1 -C.sub.4 -alkylamino
(p) di(C.sub.1 -C.sub.4 -alkyl)amino
(q) --CF.sub.3
(r) --SO.sub.2 --NHR.sup.9
(s) aryl;
(t) furyl;
R.sup.4 is H, C.sub.1 -C.sub.6 -alkyl, --CH.sub.2 -aryl or aryl;
R.sup.5 is H or --CH(R.sup.4)--O--CO--R.sup.4a wherein R.sup.4a is C.sub.1 -C.sub.6 -alkyl, aryl or --CH.sub.2 -aryl;
R.sup.6 is (a) C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.2 -C.sub.6 -alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, C.sub.3 -C.sub.7 -cycloalkyl, halo, C.sub.1 -C.sub.4 -alkoxy, --NH.sub.2, --NH(C.sub.1 -C.sub.4 -alkyl), --N(C.sub.1 -C.sub.4 -alkyl).sub.2, --NH--SO.sub.2 R.sup.4, --COOR.sup.4, --SO.sub.2 NHR.sup.9, and C.sub.1 -C.sub.4 -alkylthio,
(b) C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio, OH, perfluoro-C.sub.1 -C.sub.4 -alkyl, and halo,
(c) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.3 -alkyl wherein the cycloalkyl is unsubstituted or substituted as in (b) above,
(d) aryl, or
(e) heteroaryl;
R.sup.7 is (a) H,
(b) phenyl unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkyl, --NO.sub.2, --CF.sub.3, --SO.sub.2 NR.sup.9 R.sup.10, C.sub.1 -C.sub.4 -alkylthio, --OH, --NH.sub.2, --COOR.sup.4, C.sub.3 -C.sub.7 -cycloalkyl, and C.sub.3 -C.sub.10 -alkenyl,
(c) C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.2 -C.sub.6 -alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heteroaryl, C.sub.3 -C.sub.7 -cycloalkyl, halo, C.sub.1 -C.sub.4 -alkoxy, --NH.sub.2, --NH(C.sub.1 -C.sub.4 -alkyl), --N(C.sub.1 -C.sub.4 -alkyl).sub.2, --NH--SO.sub.2 R.sup.4, --COOR.sup.4, --SO.sub.2 NHR.sup.9, and C.sub.1 -C.sub.4 -alkylthio,
(d) heteroaryl, or
(e) C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio, --OH, --COOR.sup.4, perfluoro-C.sub.1 -C.sub.4 -alkyl, and halo;
R.sup.8 is --H, halo, --CF.sub.3, --CH.sub.3, --OCH.sub.3 or --NO.sub.2 ;
R.sup.7 and R.sup.8 when joined together form a ring with the atoms to which they are attached such that
R.sup.7 -R.sup.8 is
(a) --Y--(CH.sub.2).sub.n --Z, wherein n is 1 or 2;
Y is a single bond, --C(O)-- or --C(R.sup.14)(R.sup.15)--;
Z is a single bond, --O--, --S(O).sub.p --, --N(R.sup.16)--, --C(O)--, --CF.sub.2 -- or --C(R.sup.14)(R.sup.15)--;
and p is 0, 1 or 2
(b) ##STR35## with the proviso that:
(1) Q is a single bond or --CO--;
(2) T is a single bond or --CO--;
and
(3) at least one of Q and T is a single bond,
(c) ##STR36## (d) ##STR37## ##STR38## wherein U is --O--, --S--, --C(O)--, --CF.sub.2 -- or --CH.sub.2 --, or ##STR39## R.sup.9 is H, C.sub.1 -C.sub.5 -alkyl, aryl or --CH.sub.2 -aryl;
R.sup.10 is H, C.sub.1 -C.sub.4 -alkyl, or
R.sup.9 and R.sup.10 when together form --(CH.sub.2).sub.m -- where m is 3-6;
R.sup.11 is H, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.4 -alkenyl, C.sub.1 -C.sub.4 -alkoxy-C.sub.1 -C.sub.4 -alkyl, or --CH.sub.2 --C.sub.6 H.sub.4 R.sup.21 ;
R.sup.12 is --CN, --NO.sub.2 or --CO.sub.2 R.sup.4 ;
R.sup.13 is H, C.sub.2 -C.sub.4 -alkanoyl, C.sub.1 -C.sub.6 -alkyl, allyl, C.sub.3 -C.sub.6 -cycloalkyl, phenyl or benzyl;
R.sup.14 and R.sup.15 are independently H, C.sub.1 -C.sub.4 -alkyl, aryl, aryl-C.sub.1 -C.sub.2 -alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H or --CH.sub.2 OH;
R.sup.16 is (a) C.sub.1 -C.sub.6 -alkyl, either unsubstituted or substituted with C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkyl-S(O).sub.p --, --CF.sub.3, --OH, --CN, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H, --CONR.sup.9 R.sup.10 or --CO-aryl,
(b) C.sub.3 -C.sub.6 -alkenyl,
(c) C.sub.3 -C.sub.6 -cycloalkyl,
(d) aryl,
(e) heteroaryl,
(f) --COR.sup.20,
(g) --CO.sub.2 R.sup.20,
(h) --CONR.sup.9 R.sup.10, or
(i) --SO.sub.2 R.sup.20 ;
R.sup.17 and R.sup.18 are independently H, C.sub.1 -C.sub.4 -alkyl, aryl, aryl-C.sub.1 -C.sub.2 -alkyl, C.sub.1 -C.sub.4 -alkoxy, --CF.sub.3, halo, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H or --CH.sub.2 OH;
R.sup.19 is C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, halo, --CF.sub.3, C.sub.1 -C.sub.4 -alkyl-S(O).sub.p --, CF.sub.3 SO.sub.2 --, --CN, --NO.sub.2, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H, or --CH.sub.2 OH;
R.sup.20 is C.sub.1 -C.sub.6 -alkyl, aryl or aryl-C.sub.1 -C.sub.2 -alkyl;
R.sup.21 is H, --NO.sub.2, --NH.sub.2, --OH or --OCH.sub.3 ;
R.sup.23 is (a) phenyl, unsubstituted or substituted with one or two substituents selected from halo, --CH.sub.3 and --CF.sub.3, at least one or which occupies an ortho-position;
(b) heteroaryl, selected from the group consisting of furan-2-yl, thiophen-2-yl, benzo[b]furan-2-yl, benzo[b ]thiophene-2-yl, furan-3-yl, thiophen-3-yl, and oxazol-5-yl, unsubstituted or substituted with one or two substituents selected from halo, --CH.sub.3 and CF.sub.3 wherein at least one of the substituents is located adjacent to the carbonyl substituent or to a ring heteroatom or both;
(c) C.sub.3 -C.sub.6 -alkyl;
(d) C.sub.3 -C.sub.7 -cycloalkyl, unsubstituted or substituted at the 1- or 2-position or both with one to three substituents selected from halo, --CH.sub.3 and --CH.sub.2 CH.sub.3 ;
(e) C.sub.7 -C.sub.8 -bi- or tricycloalkyl;
(f) saturated 5- or 6-membered heterocyclyl linked through a carbon atom and containing one or two heteroatoms selected from oxygen and sulfur selected from the group consisting of tetrahydrofuroyl, 1,3-dithiolane, and 1,3-dithiane.
R.sup.24 is H, or R.sup.25,
R.sup.25 is (a) phenyl unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, --O--C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkyl, --NO.sub.2, --CF.sub.3, --SO.sub.2 NR.sup.9 R.sup.10, --S--C.sub.1 -C.sub.4 -alkyl, --OH, --NH.sub.2, --COOR.sup.4, C.sub.3 -C.sub.7 -cycloalkyl, and C.sub.3 -C.sub.10 -alkenyl,
(b) C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.2 -C.sub.6 -alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, C.sub.3 -C.sub.7 -cycloalkyl, halo, --OH, --O--C.sub.1 -C.sub.4 -alkyl, --NH.sub.2, --NH(C.sub.1 -C.sub.4 -alkyl), --N(C.sub.1 -C.sub.4 -alkyl).sub.2, --NH--SO.sub.2 R.sup.4, --COOR.sup.4, --SO.sub.2 NHR.sup.9, and --S--C.sub.1 -C.sub.4 -alkyl,
(c) an unsubstituted, monosubstituted or disubstituted aromatic 5 or 6 membered ring comprising one or two heteroatoms selected from the group consisting of N, O, and S, and wherein the substituents are members selected from the group consisting of --OH, --SH, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkyloxy, --CF.sub.3, --COOR.sup.4, halo, and NO.sub.2, or
(d) C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, --O--C.sub.1 -C.sub.4 -alkyl, --S--C.sub.1 -C.sub.4 -alkyl, --OH, --COOR.sup.4, perfluoro--C.sub.1 -C.sub.4 -alkyl, halo;
V is
(a) H,
(b) C.sub.1 -C.sub.5 -alkoxy,
(c) C.sub.1 -C.sub.5 -alkyl,
(d) hydroxy,
(e) C.sub.1 -C.sub.5 -alkyl-S(O).sub.p,
(f) --CN,
(g) --NO.sub.2,
(h) --NR.sup.9 R.sup.10 ;
(i) C.sub.1 -C.sub.5 -alkyl-CONR.sup.9 R.sup.10,
(j) --CONR.sup.9 R.sup.10
(k) --CO.sub.2 R.sup.9,
(l) C.sub.1 -C.sub.5 -alkyl-carbonyl,
(m) CF.sub.3,
(n) halogen,
(o) hydroxy-C.sub.1 -C.sub.4 -alkyl-,
(p) carboxy-C.sub.1 -C.sub.4 -alkyl-,
(q) --1H-tetrazol-5-yl,
(r) --NH--SO.sub.2 CF.sub.3,
(s) aryl,
(t) C.sub.1 -C.sub.5 -alkyl-CO.sub.2 R.sup.9,
(u) aryloxy,
(v) aryl-C.sub.1 -C.sub.3 -alkoxy,
(w) aryl-C.sub.1 -C.sub.3 -alkyl,
(x) carboxyphenyl,
(y) heteroaryl,
(z) 2-oxazolin-2-yl unsubstituted or bearing one or more C.sub.1 -C.sub.4 -alkyl substituents,
(aa) --(CH.sub.2).sub.t OCOR.sup.25,
(bb) --(CH.sub.2).sub.t OCONR.sup.24 R.sup.25,
(cc) --(CH.sub.2).sub.t NR.sup.24 COR.sup.25,
(dd) --(CH.sub.2).sub.t NR.sup.24 CO.sub.2 R.sup.25,
(ee) --(CH.sub.2).sub.t NR.sup.24 CONR.sup.24 R.sup.25,
(ff) --(CH.sub.2).sub.t NR.sup.24 CON(CH.sub.2 CH.sub.2).sub.2 L,
(gg) --(CH.sub.2).sub.t OCON(CH.sub.2 CH.sub.2).sub.2 L,
(hh) --N(CH.sub.2 CH.sub.2).sub.2 L,
(ii) --C.sub.1 -C.sub.5 -alkyl-CON(CH.sub.2 CH.sub.2).sub.2 L, or
(jj) --CON(CH.sub.2 CH.sub.2)L;
t is 0, 1 or 2;
and
L is a bond, --CH.sub.2 --, --O--, --S(O).sub.p -- or --NR.sup.9 --,
wherein heteroaryl is selected from the group consisting of pyridine, pyrimidine, pyrazine, triazine, furan, thiophene, oxazole, thiazole, imidazole, triazole and thiadiazole, which is unsubstituted or fused to a benzo group and wherein the mono- or bicyclic system can be unsubstituted or substituted with one or two substituents selected from the group consisting of C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CN, --OH, --NH.sub.2, --NH(C.sub.1-4 alkyl), --N(C.sub.1-4 alkyl).sub.2, C.sub.1-4 alkoxycarbonyl and --CO.sub.2 H.

158 more elements

Dependencies are inferred from the claim text.

Facts

Application: 07/917,642Filed 17 Jul 1992
Granted: 17 May 1994
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 215/38
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07C 311/51
Compounds containing any of the groups [IMAGE cpc-sch-C07C-0977.gif], X being a hetero atom, Y being any atom: y being a hydrogen or a carbon atom
C07D 209/08
Indoles; Hydrogenated indoles: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms…
C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates

Family

No related US applications are recorded in the indexed filing history.

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Abstract

A compound of structural formula:

##STR33## or a pharmaceutically acceptable salt thereof wherein:
A, B, C, and D are independently --CH.dbd. or --N.dbd., with the proviso that at least two of them are --CH.dbd.;
X is --O-- or --N(R.sup.7)--;
R.sup.1 is
(a) --CO.sub.2 R.sup.4,
(b) --SO.sub.3 R.sup.5,
(c) --NHSO.sub.2 CF.sub.3,
(d) --PO(OR.sup.5).sub.2,
(e) --SO.sub.2 --NH--R.sup.9,
(f) --CONHOR.sup.5,
(g) --SO.sub.2 NH-heteroaryl,
(h) --CH.sub.2 SO.sub.2 NH-heteroaryl,
(i) --SO.sub.2 NHCOR.sup.23,
(j) --CH.sub.2 SO.sub.2 NHCOR.sup.23,
(k) --CONHSO.sub.2 R.sup.23,
(l) --CH.sub.2 CONHSO.sub.2 R.sup.23,
(m) --NHSO.sub.2 NHCOR.sup.23,
(n) --NHCONHSO.sub.2 R.sup.23,
(o) --SO.sub.2 NHSO.sub.2 R.sup.23,
(p) --SO.sub.2 NHCO.sub.2 R.sup.20,
(q) --SO.sub.2 NHCONHR.sup.20, ##STR34## wherein:
Y is
(1) --CO.sub.2 R.sup.4,
(2) --SO.sub.3 R.sup.5,
(3) --NHSO.sub.2 CF.sub.3,
(4) --PO(OR.sup.5).sub.2, or
(5) --SO.sub.2 --NH--R.sup.9 ;
(6) 1H-tetrazol-5-yl;
R.sup.2a and R.sup.2b are each independently:
(a) hydrogen,
(b) halo,
(c) --NO.sub.2,
(d) --NH.sub.2,
(e) C.sub.1 -C.sub.4 -alkylamino,
(f) --SO.sub.2 NHR.sup.9,
(g) --CF.sub.3,
(h) C.sub.1 -C.sub.4 -alkyl
(i) C.sub.1 -C.sub.4 -alkoxy;
R.sup.3a is
(a) --H,
(b) halo,
(c) C.sub.1 -C.sub.6 -alkyl,
(d) C.sub.1 -C.sub.6 -alkoxy,
(e) C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.4 -alkyl;
R.sup.3b is
(a) --H,
(b) --halo,
(c) --NO.sub.2,
(d) C.sub.1 -C.sub.6 -alkyl,
(e) C.sub.1 -C.sub.5 -alkylcarbonyloxy,
(f) C.sub.3 -C.sub.6 -cycloalkyl
(g) C.sub.1 -C.sub.6 -alkoxy,
(h) --NHSO.sub.2 R.sup.4,
(i) hydroxy-C.sub.1 -C.sub.4 -alkyl,
(j) aryl-C.sub.1 -C.sub.4 -alkyl
(k) C.sub.1 -C.sub.4 -alkylthio
(l) C.sub.1 -C.sub.4 -alkylsulfinyl
(m) C.sub.1 -C.sub.4 -alkylsulfonyl
(n) --NH.sub.2
(o) C.sub.1 -C.sub.4 -alkylamino
(p) di(C.sub.1 -C.sub.4 -alkyl)amino
(q) --CF.sub.3
(r) --SO.sub.2 --NHR.sup.9
(s) aryl;
(t) furyl;
R.sup.4 is H, C.sub.1 -C.sub.6 -alkyl, --CH.sub.2 -aryl or aryl;
R.sup.5 is H or --CH(R.sup.4)--O--CO--R.sup.4a wherein R.sup.4a is C.sub.1 -C.sub.6 -alkyl, aryl or --CH.sub.2 -aryl;
R.sup.6 is (a) C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.2 -C.sub.6 -alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, C.sub.3 -C.sub.7 -cycloalkyl, halo, C.sub.1 -C.sub.4 -alkoxy, --NH.sub.2, --NH(C.sub.1 -C.sub.4 -alkyl), --N(C.sub.1 -C.sub.4 -alkyl).sub.2, --NH--SO.sub.2 R.sup.4, --COOR.sup.4, --SO.sub.2 NHR.sup.9, and C.sub.1 -C.sub.4 -alkylthio,
(b) C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio, OH, perfluoro-C.sub.1 -C.sub.4 -alkyl, and halo,
(c) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.3 -alkyl wherein the cycloalkyl is unsubstituted or substituted as in (b) above,
(d) aryl, or
(e) heteroaryl;
R.sup.7 is (a) H,
(b) phenyl unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkyl, --NO.sub.2, --CF.sub.3, --SO.sub.2 NR.sup.9 R.sup.10, C.sub.1 -C.sub.4 -alkylthio, --OH, --NH.sub.2, --COOR.sup.4, C.sub.3 -C.sub.7 -cycloalkyl, and C.sub.3 -C.sub.10 -alkenyl,
(c) C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.2 -C.sub.6 -alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heteroaryl, C.sub.3 -C.sub.7 -cycloalkyl, halo, C.sub.1 -C.sub.4 -alkoxy, --NH.sub.2, --NH(C.sub.1 -C.sub.4 -alkyl), --N(C.sub.1 -C.sub.4 -alkyl).sub.2, --NH--SO.sub.2 R.sup.4, --COOR.sup.4, --SO.sub.2 NHR.sup.9, and C.sub.1 -C.sub.4 -alkylthio,
(d) heteroaryl, or
(e) C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio, --OH, --COOR.sup.4, perfluoro-C.sub.1 -C.sub.4 -alkyl, and halo;
R.sup.8 is --H, halo, --CF.sub.3, --CH.sub.3, --OCH.sub.3 or --NO.sub.2 ;
R.sup.7 and R.sup.8 when joined together form a ring with the atoms to which they are attached such that
R.sup.7 -R.sup.8 is
(a) --Y--(CH.sub.2).sub.n --Z, wherein n is 1 or 2;
Y is a single bond, --C(O)-- or --C(R.sup.14)(R.sup.15)--;
Z is a single bond, --O--, --S(O).sub.p --, --N(R.sup.16)--, --C(O)--, --CF.sub.2 -- or --C(R.sup.14)(R.sup.15)--;
and p is 0, 1 or 2
(b) ##STR35## with the proviso that:
(1) Q is a single bond or --CO--;
(2) T is a single bond or --CO--;
and
(3) at least one of Q and T is a single bond,
(c) ##STR36## (d) ##STR37## ##STR38## wherein U is --O--, --S--, --C(O)--, --CF.sub.2 -- or --CH.sub.2 --, or ##STR39## R.sup.9 is H, C.sub.1 -C.sub.5 -alkyl, aryl or --CH.sub.2 -aryl;
R.sup.10 is H, C.sub.1 -C.sub.4 -alkyl, or
R.sup.9 and R.sup.10 when together form --(CH.sub.2).sub.m -- where m is 3-6;
R.sup.11 is H, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.4 -alkenyl, C.sub.1 -C.sub.4 -alkoxy-C.sub.1 -C.sub.4 -alkyl, or --CH.sub.2 --C.sub.6 H.sub.4 R.sup.21 ;
R.sup.12 is --CN, --NO.sub.2 or --CO.sub.2 R.sup.4 ;
R.sup.13 is H, C.sub.2 -C.sub.4 -alkanoyl, C.sub.1 -C.sub.6 -alkyl, allyl, C.sub.3 -C.sub.6 -cycloalkyl, phenyl or benzyl;
R.sup.14 and R.sup.15 are independently H, C.sub.1 -C.sub.4 -alkyl, aryl, aryl-C.sub.1 -C.sub.2 -alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H or --CH.sub.2 OH;
R.sup.16 is (a) C.sub.1 -C.sub.6 -alkyl, either unsubstituted or substituted with C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkyl-S(O).sub.p --, --CF.sub.3, --OH, --CN, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H, --CONR.sup.9 R.sup.10 or --CO-aryl,
(b) C.sub.3 -C.sub.6 -alkenyl,
(c) C.sub.3 -C.sub.6 -cycloalkyl,
(d) aryl,
(e) heteroaryl,
(f) --COR.sup.20,
(g) --CO.sub.2 R.sup.20,
(h) --CONR.sup.9 R.sup.10, or
(i) --SO.sub.2 R.sup.20 ;
R.sup.17 and R.sup.18 are independently H, C.sub.1 -C.sub.4 -alkyl, aryl, aryl-C.sub.1 -C.sub.2 -alkyl, C.sub.1 -C.sub.4 -alkoxy, --CF.sub.3, halo, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H or --CH.sub.2 OH;
R.sup.19 is C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, halo, --CF.sub.3, C.sub.1 -C.sub.4 -alkyl-S(O).sub.p --, CF.sub.3 SO.sub.2 --, --CN, --NO.sub.2, C.sub.1 -C.sub.4 -alkoxycarbonyl, --CO.sub.2 H, or --CH.sub.2 OH;
R.sup.20 is C.sub.1 -C.sub.6 -alkyl, aryl or aryl-C.sub.1 -C.sub.2 -alkyl;
R.sup.21 is H, --NO.sub.2, --NH.sub.2, --OH or --OCH.sub.3 ;
R.sup.23 is (a) phenyl, unsubstituted or substituted with one or two substituents selected from halo, --CH.sub.3 and --CF.sub.3, at least one or which occupies an ortho-position;
(b) heteroaryl, selected from the group consisting of furan-2-yl, thiophen-2-yl, benzo[b]furan-2-yl, benzo[b ]thiophene-2-yl, furan-3-yl, thiophen-3-yl, and oxazol-5-yl, unsubstituted or substituted with one or two substituents selected from halo, --CH.sub.3 and CF.sub.3 wherein at least one of the substituents is located adjacent to the carbonyl substituent or to a ring heteroatom or both;
(c) C.sub.3 -C.sub.6 -alkyl;
(d) C.sub.3 -C.sub.7 -cycloalkyl, unsubstituted or substituted at the 1- or 2-position or both with one to three substituents selected from halo, --CH.sub.3 and --CH.sub.2 CH.sub.3 ;
(e) C.sub.7 -C.sub.8 -bi- or tricycloalkyl;
(f) saturated 5- or 6-membered heterocyclyl linked through a carbon atom and containing one or two heteroatoms selected from oxygen and sulfur selected from the group consisting of tetrahydrofuroyl, 1,3-dithiolane, and 1,3-dithiane.
R.sup.24 is H, or R.sup.25,
R.sup.25 is (a) phenyl unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, --O--C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkyl, --NO.sub.2, --CF.sub.3, --SO.sub.2 NR.sup.9 R.sup.10, --S--C.sub.1 -C.sub.4 -alkyl, --OH, --NH.sub.2, --COOR.sup.4, C.sub.3 -C.sub.7 -cycloalkyl, and C.sub.3 -C.sub.10 -alkenyl,
(b) C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.2 -C.sub.6 -alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, C.sub.3 -C.sub.7 -cycloalkyl, halo, --OH, --O--C.sub.1 -C.sub.4 -alkyl, --NH.sub.2, --NH(C.sub.1 -C.sub.4 -alkyl), --N(C.sub.1 -C.sub.4 -alkyl).sub.2, --NH--SO.sub.2 R.sup.4, --COOR.sup.4, --SO.sub.2 NHR.sup.9, and --S--C.sub.1 -C.sub.4 -alkyl,
(c) an unsubstituted, monosubstituted or disubstituted aromatic 5 or 6 membered ring comprising one or two heteroatoms selected from the group consisting of N, O, and S, and wherein the substituents are members selected from the group consisting of --OH, --SH, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkyloxy, --CF.sub.3, --COOR.sup.4, halo, and NO.sub.2, or
(d) C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, --O--C.sub.1 -C.sub.4 -alkyl, --S--C.sub.1 -C.sub.4 -alkyl, --OH, --COOR.sup.4, perfluoro--C.sub.1 -C.sub.4 -alkyl, halo;
V is
(a) H,
(b) C.sub.1 -C.sub.5 -alkoxy,
(c) C.sub.1 -C.sub.5 -alkyl,
(d) hydroxy,
(e) C.sub.1 -C.sub.5 -alkyl-S(O).sub.p,
(f) --CN,
(g) --NO.sub.2,
(h) --NR.sup.9 R.sup.10 ;
(i) C.sub.1 -C.sub.5 -alkyl-CONR.sup.9 R.sup.10,
(j) --CONR.sup.9 R.sup.10
(k) --CO.sub.2 R.sup.9,
(l) C.sub.1 -C.sub.5 -alkyl-carbonyl,
(m) CF.sub.3,
(n) halogen,
(o) hydroxy-C.sub.1 -C.sub.4 -alkyl-,
(p) carboxy-C.sub.1 -C.sub.4 -alkyl-,
(q) --1H-tetrazol-5-yl,
(r) --NH--SO.sub.2 CF.sub.3,
(s) aryl,
(t) C.sub.1 -C.sub.5 -alkyl-CO.sub.2 R.sup.9,
(u) aryloxy,
(v) aryl-C.sub.1 -C.sub.3 -alkoxy,
(w) aryl-C.sub.1 -C.sub.3 -alkyl,
(x) carboxyphenyl,
(y) heteroaryl,
(z) 2-oxazolin-2-yl unsubstituted or bearing one or more C.sub.1 -C.sub.4 -alkyl substituents,
(aa) --(CH.sub.2).sub.t OCOR.sup.25,
(bb) --(CH.sub.2).sub.t OCONR.sup.24 R.sup.25,
(cc) --(CH.sub.2).sub.t NR.sup.24 COR.sup.25,
(dd) --(CH.sub.2).sub.t NR.sup.24 CO.sub.2 R.sup.25,
(ee) --(CH.sub.2).sub.t NR.sup.24 CONR.sup.24 R.sup.25,
(ff) --(CH.sub.2).sub.t NR.sup.24 CON(CH.sub.2 CH.sub.2).sub.2 L,
(gg) --(CH.sub.2).sub.t OCON(CH.sub.2 CH.sub.2).sub.2 L,
(hh) --N(CH.sub.2 CH.sub.2).sub.2 L,
(ii) --C.sub.1 -C.sub.5 -alkyl-CON(CH.sub.2 CH.sub.2).sub.2 L, or
(jj) --CON(CH.sub.2 CH.sub.2)L;
t is 0, 1 or 2;
and
L is a bond, --CH.sub.2 --, --O--, --S(O).sub.p -- or --NR.sup.9 --,
wherein heteroaryl is selected from the group consisting of pyridine, pyrimidine, pyrazine, triazine, furan, thiophene, oxazole, thiazole, imidazole, triazole and thiadiazole, which is unsubstituted or fused to a benzo group and wherein the mono- or bicyclic system can be unsubstituted or substituted with one or two substituents selected from the group consisting of C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, --CF.sub.3, halo, --NO.sub.2, --CN, --OH, --NH.sub.2, --NH(C.sub.1-4 alkyl), --N(C.sub.1-4 alkyl).sub.2, C.sub.1-4 alkoxycarbonyl and --CO.sub.2 H.

158 more elements

Facts

Application

07/917,642Filed 17 Jul 1992

Granted

17 May 1994

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 215/38
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07C 311/51
Compounds containing any of the groups [IMAGE cpc-sch-C07C-0977.gif], X being a hetero atom, Y being any atom: y being a hydrogen or a carbon atom
C07D 209/08
Indoles; Hydrogenated indoles: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms…
C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates