US 6,388,122 B1 · Tryptase inhibitor and novel guanidino derivatives

Abstract

A tryptase inhibitor comprising as an active ingredient at least one member selected from among guanidinoaliphatic acid derivatives of the formula (I), guanidinobenzoic acid derivatives of the formula (II), guanidinophenol derivatives of the formula (III), amidinophenol derivatives of the formula (IV), and novel guanidinophenol derivatives of the formula (V) (in the formulae, Gu is guanidino).

Claims16

Dependent claims

A method for the prevention and/or treatment of diseases induced by tryptase, which comprises administering to a patient an effective amount of a guanidinoaliphatic acid derivative represented by the formula (I)

(wherein R1 represents a hydrogen atom, a halogen atom, a nitro group, an alkyl group, an alkoxyl group, a carboxyl group or an alkoxycarbonyl group, and n represents an integer of 3 to 6), a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

A method for the prevention and/or treatment of diseases induced by tryptase, which comprises administering to a patient an effective amount of a guanidinophenol derivative represented by the formula (III)

(wherein R4 is hydrogen,
R5 is:
(i) C1-4 alkyl,
(ii) C1-4 alkoxy,
(iii) —COOR15a (in which R15a is hydrogen or C1-4 alkyl);
(iv) —COR25 (in which R25 is C1-4 alkyl or phenyl);
(v) —O—A5—COOR35 (in which A5 is C1-4 alkylene, R35 is hydrogen or C1-4 alkyl);
(vi) —NR45R55 (in which R45 and R55 each, independently, is hydrogen or C1-4 alkyl);
(vii) —B5—NR65R75 (in which B5 is sulfonyl or carbonyl, R65 is hydrogen, C1-4 alkyl, phenyl or C7-10 phenylalkyl, R75 is hydrogen, C1-4 alkyl, phenyl, C7-10 phenylalkyl or —D5—COOR85 (in which D5 is C1-4 alkylene, R85 is hydrogen, C1-7 alkyl or C7-10 phenylalkyl);
or R65 and R75 taken together with nitrogen neighboring thereto, is
(in which
is 4-7 membered saturated monocyclic heterocyclic ring or fuzed heterocyclic ring with benzene ring,
R95 is hydorogen or —COOR105 (in which R105 is hydrogen, C1-4 alkyl or C7-10 phenylalkyl)));
(in which R115 is hydrogen, C1-7 alkyl, or 4-14 membered monocyclic or polycyclic alkyl);
or
(in which E5 is C1-4 alkylene, R125 and R135 each, independently, is hydrogen or C1-4 alkyl)), a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

13 more elements

A method for the prevention and/or treatment of diseases induced by tryptase, which comprises administering to a patient an effective amount of a amidinophenol derivative represented by the formula (IV)

(wherein
(1) R6 is:
(i) hydrogen,
(ii) C1-4 alkyl,
(iii) C1-4 alkoxy,
(iv) C2-5 acyl,
(v) halogen,
(vi) nitro,
(vii) benzoyl or
(viii) COOR46 (in which R46 is C1-3 alkyl);
R7 is —A7—R37
wherein A7 is a bond, C1-4 alkylene or
(in which R57 and R67 each, independently, is hydrogen or C1-4 alkyl);
R37 is
(in which R77 and R87 each, independently, is
(1) hydrogen,
(2) phenyl,
(3) C7-10 phenylalkyl,
(4) phenyl or C7-10 phenylalkyl each of which is substituted by one or two substituents selected from C1-4 alkyl, halogen and R117COOR127
(in which R117 is
(a) a bond,
(b) C1-8 alkylene,
(C) C2-8 alkenylene or
(d) C2-8 alkynylene, and
R127 is
(a) hydrogen,
(b) C1-4 alkyl,
(c) C7-10 phenylalkyl,
(d) phenyl,
(e) allyl or
(f) propargyl),
(5) C1-10 alkyl,
(6) C2-10 alkenyl having one to three double bonds,
(7) C2-10 alkynyl having one or two triple bonds,
(8) R117a—COX7R127
(in which R117a is
(a) a bond,
(b) C1-8 alkylene,
(c) C2-8 alkylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
(d) C2-8 alkenylene,
(e) C4-8 alkenylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
(f) C2-8 alkynylene, or
(g) C4-8 alkynylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
X7 is oxygen or —NH—, and
R127 is the same meaning as hereinbefore defined),
(9) C1-4 alkyl which is substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one nitrogen, or
(10) C3-7 cycloalkyl);
R97 is
(1) hydrogen,
(2) C1-8 alkyl,
(3) C7-10 phenylalkyl,
(4) C2-10 alkenyl having one to three double bonds,
(5) C2-10 alkynyl having one or two triple bonds,
(6) R117—COOR127 (in which R117 and R127 are the same meaning as hereinbefore defined), or
(7) C3-7 cycloalkyl;
is 4-7 membered, mono-cyclic hetero ring containing one or two nitrogen;
R107 is
(1) hydrogen,
(2) C7-10 phenylalkyl or
(3) COOR137 (in which R137 is hydrogen, C1-4 alkyl or C7-10 phenylalkyl));
with the proviso that
(i) both R77 and R87 do not represent hydrogen at the same time, and
(ii) when at least one group in R77, R87 and R97 represents the group containing t-butyl ester, the other groups do not represent the group containing carboxy;
(2) R6 is
(i) hydrogen,
(ii) C1-4 alkyl,
(iii) C1-4 alkoxy,
(iv) C2-5 acyl,
(v) halogen,
(vi) nitro,
(vii) benzoyl, or
(viii) COOR46b (in which R46b is C1-3 alkyl);
R7 is —A7b—R37b
wherein A7b is bond, C1-4 alkylene, or
(in which R57b and R67b each, independently, is hydrogen or C1-4 alkyl);
R37b is
(in which R77b and R87b each, independently, is
(1) hydrogen,
(2) phenyl,
(3) C7-10 phenylalkyl,
(4) phenyl or C7-10 phenylalkyl each of which is substituted by one or two substituents optionally selected from C1-4 alkyl, halogen and R117b—COOR127b
(in which R117 is
a bond,
C1-8 alkylene,
C2-8 alkenylene, or
C2-8 alkynylene;
R127b is
hydrogen,
C1-4 alkyl,
C7-10 phenylalkyl,
phenyl,
allyl, or
propargyl),
(5) C1-10 alkyl,
(6) C2-10 alkenyl having one to three double bonds,
(7) C2-10 alkynyl having one or two triple bonds,
(8) R117ba—COX7bR127b
(in which R117ba is
a bond,
C1-8 alkylene,
C2-8 alkylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
C2-8 alkenylene,
C4-8 alkenylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
C2-8 alkynylene, or
C4-8 alkynylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
X7b is oxygen or —NH—, and
R127b has the same meaning as hereinbefore defined),
(9) C1-4 alkyl which is substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one nitrogen,
(10) C3-7 cycloalkyl, or
(11) C1-6 alkyl which is substituted by a C1-4 alkoxy;
R97b is
(1) hydrogen,
(2) C1-8 alkyl,
(3) C7-10 phenylalkyl,
(4) C2-10 alkenyl having one to three double bonds,
(5) C2-10 alkynyl having one or two triple bonds,
(6) R117b—COOR127b (in which R117b and R127b are same meaning as hereinbefore defined),
(7) C3-7 cycloalkyl, or
(8) C1-6 alkyl which is substituted by C1-4 alkoxy);
with the proviso that
(i) one of the groups R77b, R87b and R97b represents C1-6 alkyl which is substituted by C1-4 alkoxy,
(ii) R77b and R87b do not simultaneously represent hydrogen, and
(iii) when one of R77b, R87b and R97b represents at-butoxycarbonyl-containing group,
the other two do not represent carboxy-containing groups;
or
(3) R6 is hydrogen, C1-4 alkyl, or C1-4 alkoxy,
R7 is —A0—R7c—
wherein A0 is a single bond, C1-4 alkylene, -oxy-(C1-4)alkylene-, -thio-(C1-4)alhylene-, C2-8 alkenylene, or C2-8 alkenylene which is substituted by carboxy or by C1-4 alkoxycarbonyl,
R7c is a group of the formula:
(in which the grouping:
is a 4-10 membered hetero ring containing one or two nitrogen atoms;
R50, R60 and R70 each independently, is
(i) hydrogen,
(ii) C1-8 alkyl,
(iii) C2-8 alkenyl,
(iv) —COOR110(in which R110 is hydrogen or C1-4 alkyl unsubstituted or substituted by phenyl),
(v) —C1-8 alkylene)-COOR110(in which R110 has the same meaning as hereinbefore defined),
(vi) —(C2-8 alkenylene)-COOR110(in which R110 has the same meaning as hereinbefore defined),
(vii) C4-7 cycloalkyl,
(viii) —C1-4 alkylene)-(4-7 membered hetero ring containing one oxygen),
(ix) —C1-4 alkylene)-(4-7 membered hetero ring containing one nitrogen),
(x) phenyl,
(xi) C1-8 alkyl which is substituted by one or two phenyl,
(xii) C1-4 alkylene)-O-benzoyl,
(xiii) —C1-4 alkylene)-CONH—(C1-4 alkylene)-NR120R130,
(xiv) —C1-4 alkylene)-COO(C1-4 alkylene)-NR120R130,
(xv) —C1-4 alkylene)-COO-amidinophenyl,
(xvi) —(C1-4 alkylene)-CONH-(C1-4 alkyl which is substituted by one or two COOR110)(in which R110 has the same meaning as hereinbefore defined),
(xvii) C1-4 alkylene)-CONR120R130, or
(xviii) —(C1-4)alkoxy(C1-4)alkyl;
R80 and R90 each independently, is C1-4 alkyl or C1-4 alkylene)-phenyl,
R120 and R130 each independently, is hydrogen, C1-4 alkyl, or C2-8 alkenyl, with the provisos that:
(1) R50 and R60 in the formulae (i) and (iii), and R50, R60 and R70 in the formulae (ii) and (iv), do not represent hydrogen at the same time,
(2) when at least one substituent in R50, R60, R70 and A0 represent substituent containing —COO-t-Bu, the other groups do not represent groups containing carboxy,
(3) R120 and R130 do not represent hydrogen at the same time,
(4) when A0 is a single bond, C1-4 alkylene or vinylene which is optionally substituted by one or two C1-4 alkyl, and R7c is the formula(i) as hereinbefore described, then at least one group in R50, R60 and R70 is
(viii) —C1-4 alkylene)-(4-7 membered hetero ring containing one oxygen),
(ix) —C1 -alkylene)-(4-7 membered hetero ring containing one nitrogen),
(x) phenyl,
(xi) —(C1-8 alkyl which is substituted by one or two phenyl,
(xii) —(C1-4 alkylene)-O-benzoyl,
(xiii) —(C1-4 alkylene)-CONH—(C1-4 alkylene)-NR120R130, (in which R120 and R130 have the same meaning as hereinbefore defined),
(xiv) —(C1-4 alkylene)-COO(C1-4 alkylene)—NR120R130, (in which R120 and R130 have the same meaning as hereinbefore defined),
(xv) —(C1-4 alkylene)-COO-amidinophenyl,
(xvi) —(C1-4 alkylene)-CONH—(C1-4 alkyl which is substituted by one or two COOR110)(in which R110 has the same meaning as hereinbefore defined),
(xvii) —C1-4 alkylene)-CONR120R130, (in which R120 and R130 have the same meaning as hereinbefore defined), or
(xviii) —(C1-4)alkoxy(C1-4)alkyl;
when A0 is a bond, C1-4 alkylene or vinylene which may be optionally substituted by one or two C1-4 alkyl, and
R7c is the formula(ii) as hereinbefore defined,
then R50, R60 and R70 do not represent hydrogen),
a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

168 more elements

A guanidinophenol derivative represented by the formula (V)

(wherein A represents a group of the following formula:
(where R9 and R10 each represents independently a hydrogen atom or a C1-4 alkyl group),
R8 represents a group selected from the following formulae:
(wherein R11, R12 and R13 each represents independently
(1) a hydrogen atom,
(2) a phenyl group,
(3) a C1-4 alkyl group substituted by a phenyl group,
(4) a C1-10 alkyl group,
(5) a C1-10 alkoxyl group,
(6) a C2-10 alkenyl group having 1 to 3 double bonds,
(7) a C2-10 alkynyl group having 1 to 2 triple bonds,
(8) a group of formula:
R15—COXR16
(where R15 represents a single bond or a C1-8 alkylene group, X represents an oxygen atom or an NH-group, and R16 represents a hydrogen group, a C1-4 alkyl group, a phenyl group or a C1-4 alkyl group substituted by a phenyl group), or
(9) a C3-7 cycloalkyl group;
represents a 4-7 membered monocyclic heteroring containing 1 to 2 nitrogen atoms,
R14 represents a hydrogen, a C4-7 alkyl group substituted by a phenyl group or a group of formula:
COOR17 (wherein R17 represents a hydrogen atom, a C1-4 alkyl group or a C4 alkyl group substituted by a phenyl group);
provided that R11, R12 and R13 do not represent simultaneously hydrogen atoms, and when at least one group among R11, R12 and R13 represents a group having a t-butoxycarbonyl group, the other groups do not represent groups having a carboxyl group),
a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

17 more elements

Dependencies are inferred from the claim text.

Facts

Application

09/155,868Filed 7 Oct 1998

Priority

JP 8-11315910 Apr 1996

Granted

14 May 2002

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 211/62
Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals: attached in position 4
A61K 31/222
Of acyclic acids, e.g. pravastatin: with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/24
Having an aromatic ring attached to a carboxyl group: having an amino or nitro group
A61K 31/245
Having an amino or nitro group: amino benzoic acid types, e.g. procaine, novocaine

Abstract

Claims16

Dependent claims

(wherein R1 represents a hydrogen atom, a halogen atom, a nitro group, an alkyl group, an alkoxyl group, a carboxyl group or an alkoxycarbonyl group, and n represents an integer of 3 to 6), a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

(wherein R4 is hydrogen,
R5 is:
(i) C1-4 alkyl,
(ii) C1-4 alkoxy,
(iii) —COOR15a (in which R15a is hydrogen or C1-4 alkyl);
(iv) —COR25 (in which R25 is C1-4 alkyl or phenyl);
(v) —O—A5—COOR35 (in which A5 is C1-4 alkylene, R35 is hydrogen or C1-4 alkyl);
(vi) —NR45R55 (in which R45 and R55 each, independently, is hydrogen or C1-4 alkyl);
(vii) —B5—NR65R75 (in which B5 is sulfonyl or carbonyl, R65 is hydrogen, C1-4 alkyl, phenyl or C7-10 phenylalkyl, R75 is hydrogen, C1-4 alkyl, phenyl, C7-10 phenylalkyl or —D5—COOR85 (in which D5 is C1-4 alkylene, R85 is hydrogen, C1-7 alkyl or C7-10 phenylalkyl);
or R65 and R75 taken together with nitrogen neighboring thereto, is
(in which
is 4-7 membered saturated monocyclic heterocyclic ring or fuzed heterocyclic ring with benzene ring,
R95 is hydorogen or —COOR105 (in which R105 is hydrogen, C1-4 alkyl or C7-10 phenylalkyl)));
(in which R115 is hydrogen, C1-7 alkyl, or 4-14 membered monocyclic or polycyclic alkyl);
or
(in which E5 is C1-4 alkylene, R125 and R135 each, independently, is hydrogen or C1-4 alkyl)), a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

13 more elements

(wherein
(1) R6 is:
(i) hydrogen,
(ii) C1-4 alkyl,
(iii) C1-4 alkoxy,
(iv) C2-5 acyl,
(v) halogen,
(vi) nitro,
(vii) benzoyl or
(viii) COOR46 (in which R46 is C1-3 alkyl);
R7 is —A7—R37
wherein A7 is a bond, C1-4 alkylene or
(in which R57 and R67 each, independently, is hydrogen or C1-4 alkyl);
R37 is
(in which R77 and R87 each, independently, is
(1) hydrogen,
(2) phenyl,
(3) C7-10 phenylalkyl,
(4) phenyl or C7-10 phenylalkyl each of which is substituted by one or two substituents selected from C1-4 alkyl, halogen and R117COOR127
(in which R117 is
(a) a bond,
(b) C1-8 alkylene,
(C) C2-8 alkenylene or
(d) C2-8 alkynylene, and
R127 is
(a) hydrogen,
(b) C1-4 alkyl,
(c) C7-10 phenylalkyl,
(d) phenyl,
(e) allyl or
(f) propargyl),
(5) C1-10 alkyl,
(6) C2-10 alkenyl having one to three double bonds,
(7) C2-10 alkynyl having one or two triple bonds,
(8) R117a—COX7R127
(in which R117a is
(a) a bond,
(b) C1-8 alkylene,
(c) C2-8 alkylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
(d) C2-8 alkenylene,
(e) C4-8 alkenylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
(f) C2-8 alkynylene, or
(g) C4-8 alkynylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
X7 is oxygen or —NH—, and
R127 is the same meaning as hereinbefore defined),
(9) C1-4 alkyl which is substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one nitrogen, or
(10) C3-7 cycloalkyl);
R97 is
(1) hydrogen,
(2) C1-8 alkyl,
(3) C7-10 phenylalkyl,
(4) C2-10 alkenyl having one to three double bonds,
(5) C2-10 alkynyl having one or two triple bonds,
(6) R117—COOR127 (in which R117 and R127 are the same meaning as hereinbefore defined), or
(7) C3-7 cycloalkyl;
is 4-7 membered, mono-cyclic hetero ring containing one or two nitrogen;
R107 is
(1) hydrogen,
(2) C7-10 phenylalkyl or
(3) COOR137 (in which R137 is hydrogen, C1-4 alkyl or C7-10 phenylalkyl));
with the proviso that
(i) both R77 and R87 do not represent hydrogen at the same time, and
(ii) when at least one group in R77, R87 and R97 represents the group containing t-butyl ester, the other groups do not represent the group containing carboxy;
(2) R6 is
(i) hydrogen,
(ii) C1-4 alkyl,
(iii) C1-4 alkoxy,
(iv) C2-5 acyl,
(v) halogen,
(vi) nitro,
(vii) benzoyl, or
(viii) COOR46b (in which R46b is C1-3 alkyl);
R7 is —A7b—R37b
wherein A7b is bond, C1-4 alkylene, or
(in which R57b and R67b each, independently, is hydrogen or C1-4 alkyl);
R37b is
(in which R77b and R87b each, independently, is
(1) hydrogen,
(2) phenyl,
(3) C7-10 phenylalkyl,
(4) phenyl or C7-10 phenylalkyl each of which is substituted by one or two substituents optionally selected from C1-4 alkyl, halogen and R117b—COOR127b
(in which R117 is
a bond,
C1-8 alkylene,
C2-8 alkenylene, or
C2-8 alkynylene;
R127b is
hydrogen,
C1-4 alkyl,
C7-10 phenylalkyl,
phenyl,
allyl, or
propargyl),
(5) C1-10 alkyl,
(6) C2-10 alkenyl having one to three double bonds,
(7) C2-10 alkynyl having one or two triple bonds,
(8) R117ba—COX7bR127b
(in which R117ba is
a bond,
C1-8 alkylene,
C2-8 alkylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
C2-8 alkenylene,
C4-8 alkenylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
C2-8 alkynylene, or
C4-8 alkynylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
X7b is oxygen or —NH—, and
R127b has the same meaning as hereinbefore defined),
(9) C1-4 alkyl which is substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one nitrogen,
(10) C3-7 cycloalkyl, or
(11) C1-6 alkyl which is substituted by a C1-4 alkoxy;
R97b is
(1) hydrogen,
(2) C1-8 alkyl,
(3) C7-10 phenylalkyl,
(4) C2-10 alkenyl having one to three double bonds,
(5) C2-10 alkynyl having one or two triple bonds,
(6) R117b—COOR127b (in which R117b and R127b are same meaning as hereinbefore defined),
(7) C3-7 cycloalkyl, or
(8) C1-6 alkyl which is substituted by C1-4 alkoxy);
with the proviso that
(i) one of the groups R77b, R87b and R97b represents C1-6 alkyl which is substituted by C1-4 alkoxy,
(ii) R77b and R87b do not simultaneously represent hydrogen, and
(iii) when one of R77b, R87b and R97b represents at-butoxycarbonyl-containing group,
the other two do not represent carboxy-containing groups;
or
(3) R6 is hydrogen, C1-4 alkyl, or C1-4 alkoxy,
R7 is —A0—R7c—
wherein A0 is a single bond, C1-4 alkylene, -oxy-(C1-4)alkylene-, -thio-(C1-4)alhylene-, C2-8 alkenylene, or C2-8 alkenylene which is substituted by carboxy or by C1-4 alkoxycarbonyl,
R7c is a group of the formula:
(in which the grouping:
is a 4-10 membered hetero ring containing one or two nitrogen atoms;
R50, R60 and R70 each independently, is
(i) hydrogen,
(ii) C1-8 alkyl,
(iii) C2-8 alkenyl,
(iv) —COOR110(in which R110 is hydrogen or C1-4 alkyl unsubstituted or substituted by phenyl),
(v) —C1-8 alkylene)-COOR110(in which R110 has the same meaning as hereinbefore defined),
(vi) —(C2-8 alkenylene)-COOR110(in which R110 has the same meaning as hereinbefore defined),
(vii) C4-7 cycloalkyl,
(viii) —C1-4 alkylene)-(4-7 membered hetero ring containing one oxygen),
(ix) —C1-4 alkylene)-(4-7 membered hetero ring containing one nitrogen),
(x) phenyl,
(xi) C1-8 alkyl which is substituted by one or two phenyl,
(xii) C1-4 alkylene)-O-benzoyl,
(xiii) —C1-4 alkylene)-CONH—(C1-4 alkylene)-NR120R130,
(xiv) —C1-4 alkylene)-COO(C1-4 alkylene)-NR120R130,
(xv) —C1-4 alkylene)-COO-amidinophenyl,
(xvi) —(C1-4 alkylene)-CONH-(C1-4 alkyl which is substituted by one or two COOR110)(in which R110 has the same meaning as hereinbefore defined),
(xvii) C1-4 alkylene)-CONR120R130, or
(xviii) —(C1-4)alkoxy(C1-4)alkyl;
R80 and R90 each independently, is C1-4 alkyl or C1-4 alkylene)-phenyl,
R120 and R130 each independently, is hydrogen, C1-4 alkyl, or C2-8 alkenyl, with the provisos that:
(1) R50 and R60 in the formulae (i) and (iii), and R50, R60 and R70 in the formulae (ii) and (iv), do not represent hydrogen at the same time,
(2) when at least one substituent in R50, R60, R70 and A0 represent substituent containing —COO-t-Bu, the other groups do not represent groups containing carboxy,
(3) R120 and R130 do not represent hydrogen at the same time,
(4) when A0 is a single bond, C1-4 alkylene or vinylene which is optionally substituted by one or two C1-4 alkyl, and R7c is the formula(i) as hereinbefore described, then at least one group in R50, R60 and R70 is
(viii) —C1-4 alkylene)-(4-7 membered hetero ring containing one oxygen),
(ix) —C1 -alkylene)-(4-7 membered hetero ring containing one nitrogen),
(x) phenyl,
(xi) —(C1-8 alkyl which is substituted by one or two phenyl,
(xii) —(C1-4 alkylene)-O-benzoyl,
(xiii) —(C1-4 alkylene)-CONH—(C1-4 alkylene)-NR120R130, (in which R120 and R130 have the same meaning as hereinbefore defined),
(xiv) —(C1-4 alkylene)-COO(C1-4 alkylene)—NR120R130, (in which R120 and R130 have the same meaning as hereinbefore defined),
(xv) —(C1-4 alkylene)-COO-amidinophenyl,
(xvi) —(C1-4 alkylene)-CONH—(C1-4 alkyl which is substituted by one or two COOR110)(in which R110 has the same meaning as hereinbefore defined),
(xvii) —C1-4 alkylene)-CONR120R130, (in which R120 and R130 have the same meaning as hereinbefore defined), or
(xviii) —(C1-4)alkoxy(C1-4)alkyl;
when A0 is a bond, C1-4 alkylene or vinylene which may be optionally substituted by one or two C1-4 alkyl, and
R7c is the formula(ii) as hereinbefore defined,
then R50, R60 and R70 do not represent hydrogen),
a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

168 more elements

A guanidinophenol derivative represented by the formula (V)

(wherein A represents a group of the following formula:
(where R9 and R10 each represents independently a hydrogen atom or a C1-4 alkyl group),
R8 represents a group selected from the following formulae:
(wherein R11, R12 and R13 each represents independently
(1) a hydrogen atom,
(2) a phenyl group,
(3) a C1-4 alkyl group substituted by a phenyl group,
(4) a C1-10 alkyl group,
(5) a C1-10 alkoxyl group,
(6) a C2-10 alkenyl group having 1 to 3 double bonds,
(7) a C2-10 alkynyl group having 1 to 2 triple bonds,
(8) a group of formula:
R15—COXR16
(where R15 represents a single bond or a C1-8 alkylene group, X represents an oxygen atom or an NH-group, and R16 represents a hydrogen group, a C1-4 alkyl group, a phenyl group or a C1-4 alkyl group substituted by a phenyl group), or
(9) a C3-7 cycloalkyl group;
represents a 4-7 membered monocyclic heteroring containing 1 to 2 nitrogen atoms,
R14 represents a hydrogen, a C4-7 alkyl group substituted by a phenyl group or a group of formula:
COOR17 (wherein R17 represents a hydrogen atom, a C1-4 alkyl group or a C4 alkyl group substituted by a phenyl group);
provided that R11, R12 and R13 do not represent simultaneously hydrogen atoms, and when at least one group among R11, R12 and R13 represents a group having a t-butoxycarbonyl group, the other groups do not represent groups having a carboxyl group),
a nontoxic salt thereof or an acid addition salt, or a hydrate thereof.

17 more elements

Dependencies are inferred from the claim text.

Tryptase inhibitor and novel guanidino derivatives

Life of this patent

Abstract

Claims16

Tryptase inhibitor and novel guanidino derivatives

Life of this patent

Abstract

Claims16