Condensed heterocyclic compounds useful for inhibiting acyl-CoA
AssigneeTakeda Chemical Industries, Ltd.
InventorsHideaki Natsugari, Yasuo Sugiyama, Yoshinori Ikeura
Life of this patent
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Abstract
Novel compound represented by the formula: ##STR1## wherein ring A, ring B and ring C each stands for an optionally substituted benzene ring; X stands for --NR-- wherein R stands for hydrogen atom or an optionally substituted hydrocarbon group, --O-- or --S--; Y stands for --(CH.sub.2)n-- wherein n denotes 1 or 2 or --NH--; and R.sup.a stands for a hydrogen atom or an optionally substituted hydrocarbon group, provided that when ring C is unsubstituted or substituted only at para-position, ring B is substituted at least at ortho-position or a salt thereof which have an excellent acyl-CoA: cholesterol acyltransferase inhibiting action and cholesterol-lowering activity, their production and medicinal use.
Claims14
A compound represented by the formula ##STR22## wherein rings, A, B and C, are respectively a benzene ring which may be substituted with one to four substituents selected from the group consisting of (i) a halogen, (ii) an optionally halogenated C.sub.1-4 alkyl, (iii) an optionally halogenated C.sub.1-4 alkoxy, (iv) an amino, (v) a mono- or di-C.sub.1-4 alkylamino, (vi) a C.sub.1-3 acyloxy, and (vii) a hydroxyl;
- X is --O--;
- Y is --(CH.sub.2)n-- wherein n denotes one or two, or --NH--;
- and
- R.sup.a is (i) a hydrogen atom or
- (ii) a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl or C.sub.6-14 aryl group which may be substituted with one to four substituents selected from the group consisting of (a) halogen, (b) C.sub.3-6 cycloalkyl, (c) C.sub.6-10 aryl, (d) amino optionally substituted with one or two C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl or C.sub.6-10 aryl, (e) hydroxyl, (f) optionally halogenated C.sub.1-4 alkoxy, (g) C.sub.1-4 acyl, (h) C.sub.1-4 acyloxy, (i) cyano, (j) carboxyl optionally protected by C.sub.1-4 alkyl or C.sub.7-11 aralkyl, (k) carbamoyl, (1) mercapto, (m) C.sub.1-4 alkylthio, (n) sulfo and (o) C.sub.1-4 alkylsulfonyl, provided that when ring C is unsubstituted or substituted only at para-position, ring B is substituted at least at ortho-position, or a salt thereof.
A compound selected from the group consisting of N-[2,6-bis(1-methylethyl)phenyl]-5-chloro-3-(2-methylphenyl)-2-benzofurana cetamide, 5-chloro-N-(2,6-dimethoxyphenyl)-3-(2-methylphenyl)-2-benzofuranacetamide, N-[2,6-bis(1methylethyl)phenyl]-5-chloro-3-phenyl-2-benzofuranacetamide, N-[2,6-bis(1-methylethyl)phenyl]-N,-[5-chloro-3-(2-methylphenyl)-2-benzofu ryl]urea, 5-chloro-N-(2,6-diethoxyphenyl)-3-(2-methylphenyl)-2-benzofuranacetamide, N-[5-chloro-3-(2-methylphenyl)-2-benzofuryl]-N,-(2,6-dimethoxyphenyl)urea, N-[5-chloro-3-(2-methylphenyl)-2-benzofuryl]-N'-(2,6-diethoxyphenyl N-[2,6-bis(1-methylethyl)phenyl]-5-chloro-3-(2-trifluoromethylphenyl)-2-be nzofuranacetamide, 5-chloro-N- (2,6diethoxyphenyl)-3- (2-trifluoromethylphenyl) -2benzofuranacetamide, N-[2,6-bis(1-methylethyl)phenyl]-N'-[5-chloro-3-(2-trifluoromethylphenyl)- 2-benzofuryl]urea and N-[5-chloro-3-(2-trifluoromethylphenyl)-2-benzofuryl]-N'-(2,6-diethoxyphen yl) urea.
A composition for inhibiting acyl-CoA;
- cholesterol acyltransferase which comprises an effective amount of a compound of the formula:
- ##STR27## wherein rings, A, B' and C', are respectively a benzene ring which may be substituted with one to four substituents selected from the group consisting of (i) a halogen, (ii) an optionally halogenated C.sub.1-4 alkyl, (iii) an optionally halogenated C.sub.1-4 alkoxy, (iv) an amino, (v) a mono- or di-C.sub.1-4 alkylamino, (vi) a C.sub.1-3 acyloxy, and (vii) a hydroxyl;
- X is --O--;
- Y is --(CH.sub.2)n-- wherein n denotes one or two, or --NH--;
- and
- R.sup.a is (i) a hydrogen atom or
- (ii) a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl or C.sub.1-4 aryl group which may be substituted with one to four substituents selected from the group consisting of (a) halogen, (b) C.sub.3-6 cycloalkyl, (c) C.sub.6-10 aryl, (d) amino optionally substituted with one or two C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl or C.sub.6-10 aryl, (e) hydroxyl, (f) optionally halogenated C.sub.1-4 alkoxy, (g) C.sub.1-4 acyl, (h) C.sub.1-4 acyloxy, (i) cyano, (j) carboxyl optionally protected by C.sub.1-4 alkyl or C.sub.7-11 aralkyl, (k) carbamoyl, (1) mercapto, (m) C.sub.1-4 alkylthio, (n) sulfo and (o) C.sub.1-4 alkylsulfonyl, provided that when ring C is unsubstituted or substituted only at para-position, ring B is substituted at least at ortho-position, or a pharmaceutically acceptable salt and a physiologically acceptable carrier.
A composition for lowering cholesterol in blood which comprises an effective amount of a compound of the formula:
- ##STR28## wherein rings A, B' and C', are respective a benzene ring which may be substituted with one to four substituents selected from the group consisting of (i) a halogen, (ii) an optionally halogenated C.sub.1-4 alkyl, (iii) an optionally halogenated C.sub.1-4 alkoxy, (iv) an amino, (v) a mono- or di-C.sub.1-4 alkylamino, (vi) a C.sub.1-3 acyloxy, and (vii) a hydroxyl;
- X is --O--;
- Y is --(CH.sub.2)n-- wherein n denotes one or two, or --NH--;
- and
- R.sup.a is (i) a hydrogen atom or
- (ii) a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-5 cycloalkyl or C.sub.6-14 aryl group which may be substituted with one to four substituents selected from the group consisting of (a) halogen, (b) C.sub.3-6 cycloalkyl, (c) C.sub.6-10 aryl, (d) amino optionally substituted with one or two C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl or C.sub.1-4 aryl, (e) hydroxyl, (f) optionally halogenated C.sub.1-4 alkoxy, (g) C.sub.1-4 acyl, (h) C.sub.1-4 acyloxy, (i) cyano, (j) carboxyl optionally protected by C.sub.1-4 alkyl or C.sub.7-11 aralkyl, (k) carbamoyl, (1) mercapto, (m) C.sub.1-4 alkylthio, (n) sulfo and (o) C.sub.1-4 alkylsulfonyl, provided that when ring C is unsubstituted or substituted only at para-position, ring B is substituted at least at ortho-position, or a pharmaceutically acceptable salt and a physiologically acceptable carrier.
A method for treating hypercholesterolemia in mammals which comprises administering to a mammal in need thereof an effective amount of a compound of the formula:
- wherein ring A, ring B' and ring C' respectively stand for a benzene ring which may be substituted with one to four substituents selected from the group consisting of (i) a halogen, (ii) an optionally halogenated C.sub.1-4 alkyl, (iii) an optionally halogenated C.sub.1-4 alkoxy, (iv) an amino, (v) a mono- or di-C.sub.1-4 alkylamino, (vi) a C.sub.1-3 acyloxy, and (vii) a hydroxyl;
- X is --O--;
- Y is --(CH.sub.2)n-- wherein n denotes one or two, or --NH--;
- and
- R.sup.a is (i) a hydrogen atom or
- (ii) a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl or C.sub.6-14 aryl group which may be substituted with one to four substituents selected from the group consisting of (a) halogen, (b) C.sub.3-6 cycloalkyl, (C) C.sub.6-10 aryl, (d) amino optionally substituted with one or two C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl or C.sub.6-10 aryl, (e) hydroxyl, (f) optionally halogenated C.sub.1-4 alkoxy, (g) C.sub.1-4 acyl, (h) C.sub.1-4 acyloxy, (i) cyano, (j) carboxyl optionally protected by C.sub.1-4 alkyl or C.sub.7-11 aralkyl, (k) carbamoyl, (1) mercapto, (m) C.sub.1-4 alkylthio, (n) sulfo and (o) C.sub.1-4 alkylsulfonyl, or a pharmaceutically acceptable salt.
Dependencies are inferred from the claim text.