US 2006/0079563 A1Published application

Cyclic protein tyrosine kinase inhibitors

AssigneeBristol-Myers Squibb Company

InventorsJagabandhu Das, Ramesh Padmanabha, Ping Chen, Derek Norris, Arthur Doweyko, Joel Barrish, John Wityak

Life of this patent

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Abstract

Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.

Claims22

Dependent claims

A compound of formula I or salt thereof

where
Q is thiazole optionally substituted with R1;
Z is a single bond;
X1 and X2 together form ═O;
R1 is
(1) hydrogen or
where R6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, C(O)qRP, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H or S(O)qR6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NR7R8;
(10) -Z4-N(R9)-Z5-NR10R11;
(11)-Z4-N(R12)-Z5-R6;
(12) —P(O)(OR6)2;
R2 is hydrogen, R6, -Z4-R6 or -Z13-NR7R8;
R3 is -Z4-R6 where Z4 is a single bond and R6 is heteroaryl optionally substituted with groups Z1, Z2 and one or more groups Z3;
R4 and R5
(1) are each independently hydrogen or R6;
(2) -Z4-N(R9)-Z5-NR10R11;
(3) —N(R9)Z4R6;
or
(4) together with the nitrogen atom to which they are attached complete a 3- to 8-membered saturated or unsaturated heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3, which heterocyclic ring may optionally have fused to it a benzene ring itself unsubstituted or substituted with Z1, Z2 and Z3;
R7, R8, R9, R10, R11 and R12
(1) are each independently hydrogen or R6;
(2) R7 and R8 may together be alkylene, alkenylene or heteroalkyl, completing a 3- to 8-membered saturated or unsaturated ring with the nitrogen atom to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R11 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
R13 is
(1) cyano;
(2) nitro;
(3) —NH2;
(4) —NHOalkyl;
(5) —OH;
(6) —NHOaryl;
(7) —NHCOOalkyl;
(8) —NHCOOaryl;
(9) —NHSO2alkyl;
(10) —NHSO2aryl;
(11) aryl;
(12) heteroaryl;
(13) -Oalkyl;
or
(14) -Oaryl;
R14 is
(1) —NO2;
(2) —COOalkyl;
or
(3) —COOaryl;
R15 is
(1) hydrogen;
(2) alkyl;
(3) aryl;
(4) arylalkyl;
or
(5) cycloalkyl;
Z1, Z2 and Z3 are each independently
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (16) of the definition of Z1, Z2 and Z3;
(2) —OH or —OZ6;
(3) —SH or —SZ6;
(4) C(O)qH, C(O)qZ6, or —O—C(O)qZ6;
(5) —SO3H, —S(O)qZ6;
or S(O)qN(Z9)Z6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NZ7Z8;
(10) -Z4-N(Z9)-Z5-NZ7Z8;
(11) -Z4-N(Z10)-Z5-Z6;
(12) -Z4-N(Z10)-Z5-H;
(13) oxo;
(14) —O—C(O)-Z6;
(15) any two of Z1, Z2, and Z3 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
or
(16) any two of Z1, Z2, and Z3 may together be —O—(CH2)r—O—, where r is 1 to 5, completing a 4- to 8-membered ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12-;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
or
(8) -Z11-C(O)—O-Z12-;
Z7, Z8, Z9 and Z10
(1) are each independently hydrogen or Z6;
(2) Z7 and Z8, or Z6 and Z10, may together be alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) Z7 or Z8, together with Z9, may be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
and
Z13 is
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12—;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
(8) -Z11-C(O)—O-Z12-;
(9) —C(NR13)—;
(10) —C(CHR14)—;
or
(111) —C(C(R14)2)—
provided said compound is other than a compound of formula (vii)
where
R3e is pyridyl or pryimidinyl optionally substituted with halogen or alkyl;
R50 and R5, are each independently hydrogen, halogen or alkyl;
R52 and R53 are each independently hydrogen, halogen, alkyl or haloalkyl;
R54 and R56 are each independently hydrogen, halogen, alkyl, nitro or amino;
R55 is hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, or alkoxycarbonyl;
and
n is zero or 1.

121 more elements

A compound of formula I or salt thereof

where
Q is thiazole optionally substituted with R1;
Z is a single bond;
X, and X2 together form ═O;
R1 is
(1) hydrogen or R6,
where R6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —O;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H or —S(O)qR6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NR7R8;
(10) -Z4-N(R9)-Z5-NR10R11;
(11) -Z4-N(R12)-Z5-R6;
(12) —P(O)(OR6)2;
R2 is hydrogen, R6, -Z4-R6 or -Z13-NR7R8;
R3 is -Z4-R6 where Z4 is a single bond and R6 is aryl optionally substituted with groups Z1 and Z2 and further substituted with at least one group Z3 where Z3 is other than hydrogen;
R4 and R5
(1) are each independently hydrogen or R6;
(2) -Z4-N(R9)-Z5-NR10R11;
(3) —N(R9)Z4R6;
or
(4) together with the nitrogen atom to which they are attached complete a 3- to 8-membered saturated or unsaturated heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3, which heterocyclic ring may optionally have fused to it a benzene ring itself unsubstituted or substituted with Z1, Z2 and Z3;
R7, R8, R9, R10, R1 and R12
(1) are each independently hydrogen or R6;
(2) R7 and R8 may together be alkylene, alkenylene or heteroalkyl, completing a 3- to 8-membered saturated or unsaturated ring with the nitrogen atom to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R1 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
R13 is
(1) cyano;
(2) nitro;
(3) —NH2;
(4) —NHOalkyl;
(5) —OH;
(6) —NHOaryl;
(7) —NHCOOalkyl;
(8) —NHCOOaryl;
(9) —NHSO2alkyl;
(10) —NHSO2aryl;
(11) aryl;
(12) heteroaryl;
(13) -Oalkyl;
or
(14) -Oaryl;
R14 is
(1) —NO2;
(2) —COOalkyl;
or
(3) —COOaryl;
R15 is
(1) hydrogen;
(2) alkyl;
(3) aryl;
(4) arylalkyl;
or
(5) cycloalkyl;
Z1, Z2 and Z3 are each independently
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (16) of the definition of Z1, Z2 and Z3;
(2) —OH or —OZ6;
(3) —SH or —SZ6;
(4) C(O)qH, —C(O)qZ6, or —O—C(O)qZ6;
(5) —SO3H, —S(O)qZ6;
or S(O)qN(Z9)Z6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NZ7Z8;
(10) -Z4-N(7) -Z5-NZ7Z8;
(11) -Z4-N(Z10)-Z5-Z6;
(12) -Z4-N(Z10)-Z5-H;
(13) oxo;
(14) —O—C(O)-Z6;
(15) any two of Z1, Z2, and Z3 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
or
(16) any two of Z1, Z2, and Z3 may together be —O—(CH2)r—O—, where r is 1 to 5, completing a 4- to 8-membered ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12-;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
or
(8) -Z11-C(O)—O-Z12-;
Z7, Z8, Z9 and Z10
(1) are each independently hydrogen or Z6;
(2) Z7 and Z8, or Z6 and Z10, may together be alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) Z7 or Z8, together with Z9, may be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
and
Z13 is
(1) a single bond;
(2) -Z11S(O)q-Z12-;
(3) -Z11-C(O)-Z12-;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
(8) -Z11-C(O)—O-Z12-;
(9) —C(NR13)—;
(10) —C(CHR14)—;
or
(11) —C(C(R14)2)—.

112 more elements

A compound of formula II or salt thereof

where
n is 1;
X3 is oxygen;
A is nitrogen;
B is sulfur;
R1 is
(1) hydrogen or R6,
where R6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z), Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H or S(O)qR6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NR7R8;
(10) -Z4-N(R9)-Z5-NR10R11;
(11) -Z4-N(R12)-Z5-R6;
(12) —P(O)(OR6)2;
R2 is hydrogen, R6, -Z4-R6 or -Z13—NR7R8;
R3 is -Z4-R6 where Z4 is a single bond and R6 is
(a) aryl optionally substituted with groups Z, and Z2 and further substituted with at least one group Z3 where Z3 is other than hydrogen;
or
(b) heteroaryl optionally substituted with groups Z1, Z2 and one or more groups Z3;
R4 and R5
(1) are each independently hydrogen or R6;
(2) -Z4-N(R9)-Z5-NR10R11;
(3) —N(R9)Z4R6;
or
(4) together with the nitrogen atom to which they are attached complete a 3- to 8-membered saturated or unsaturated heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3, which heterocyclic ring may optionally have fused to it a benzene ring itself unsubstituted or substituted with Z1, Z2 and Z3;
R7, R8, R9, R10, R1, and R12
(1) are each independently hydrogen or R6;
(2) R7 and R8 may together be alkylene, alkenylene or heteroalkyl, completing a 3- to 8-membered saturated or unsaturated ring with the nitrogen atom to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R11 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
R13 is
(1) cyano;
(2) nitro;
(3) —NH2;
(4) —NHOalkyl;
(5) —OH;
(6) —NHOaryl;
(7) —NHCOOalkyl;
(8) —NHCOOaryl;
(9) —NHSO2alkyl;
(10) —NHSO2aryl;
(11) aryl;
(12) heteroaryl;
(13) -Oalkyl;
or
(14) -Oaryl;
R14 is
(1) —NO2;
(2) —COOalkyl;
or
(3) —COOaryl;
R15 is
(1) hydrogen;
(2) alkyl;
(3) aryl;
(4) arylalkyl;
or
(5) cycloalkyl;
Z1, Z2 and Z3 are each independently
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (16) of the definition of Z1, Z2 and Z3;
(2) —OH or —OZ6;
(3) —SH or —SZ6;
(4) C(O)qH, —C(O)qZ6, or —O—C(O)qZ6;
(5) —SO3H, —S(O)qZ6;
or S(O)qN(Z9)Z6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NZ7Z8;
(10) -Z4-N(Z9)-Z5-NZ7Z8;
(11)-Z4-N(Z10)-Z5-Z6;
(12) -Z4-N(Z10)-Z5-H;
(13) oxo;
(14) —O—C(O)-Z6;
(15) any two of Z1, Z2, and Z3 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
or
(16) any two of Z1, Z2, and Z3 may together be —O—(CH2)r—O—, where r is 1 to 5, completing a 4- to 8-membered ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12-;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12—;
(7) -Z11-O—C(O)-Z12-;
or
(8) -Z11-C(O)—O-Z12-;
Z7, Z8, Z9 and Z10
(1) are each independently hydrogen or Z6;
(2) Z7 and Z8, or Z6 and Z10, may together be alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) Z7 or Z8, together with Z9, may be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
and
Z13 is
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12-;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
(8) -Z11-C(O)—O-Z12-;
(9) —C(NR13)—;
(10) —C(CHR14)—;
or
(11) —C(C(R14)2)—.
providing that said compound is other than
a compound of formula (vii)
where
R3e is phenyl, pyridyl or pryimidinyl optionally substituted with halogen or alkyl;
R50 and R51 are each independently hydrogen, halogen or alkyl;
R52 and R53 are each independently hydrogen, halogen, alkyl or haloalkyl;
R54 and R56 are each independently hydrogen, halogen, alkyl, nitro or amino;
R55 is hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, or alkoxycarbonyl;
and
n is zero or l.

126 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/271,626Filed 10 Nov 2005
Priority: 15 Apr 1999
Published: 13 Apr 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification37 codes

C07D 277/56
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,…:…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 5/14
Drugs for disorders of the endocrine system: of the thyroid hormones, e.g. T3, T4
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

Family

Application60/129,510Us provisional application · filed 15 Apr 1999
Application09/548,929Continuation · filed 13 Apr 2000
Application10/378,373Continuation · filed 3 Mar 2003
Application11/271,626Continuation · filed 10 Nov 2005
US 2004/0077875 A1Published application
US 6,596,746 B1Related patent
US 8,716,323 B2Related patent
US 2006/0079563 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula I or salt thereof

where
Q is thiazole optionally substituted with R1;
Z is a single bond;
X1 and X2 together form ═O;
R1 is
(1) hydrogen or
where R6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, C(O)qRP, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H or S(O)qR6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NR7R8;
(10) -Z4-N(R9)-Z5-NR10R11;
(11)-Z4-N(R12)-Z5-R6;
(12) —P(O)(OR6)2;
R2 is hydrogen, R6, -Z4-R6 or -Z13-NR7R8;
R3 is -Z4-R6 where Z4 is a single bond and R6 is heteroaryl optionally substituted with groups Z1, Z2 and one or more groups Z3;
R4 and R5
(1) are each independently hydrogen or R6;
(2) -Z4-N(R9)-Z5-NR10R11;
(3) —N(R9)Z4R6;
or
(4) together with the nitrogen atom to which they are attached complete a 3- to 8-membered saturated or unsaturated heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3, which heterocyclic ring may optionally have fused to it a benzene ring itself unsubstituted or substituted with Z1, Z2 and Z3;
R7, R8, R9, R10, R11 and R12
(1) are each independently hydrogen or R6;
(2) R7 and R8 may together be alkylene, alkenylene or heteroalkyl, completing a 3- to 8-membered saturated or unsaturated ring with the nitrogen atom to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R11 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
R13 is
(1) cyano;
(2) nitro;
(3) —NH2;
(4) —NHOalkyl;
(5) —OH;
(6) —NHOaryl;
(7) —NHCOOalkyl;
(8) —NHCOOaryl;
(9) —NHSO2alkyl;
(10) —NHSO2aryl;
(11) aryl;
(12) heteroaryl;
(13) -Oalkyl;
or
(14) -Oaryl;
R14 is
(1) —NO2;
(2) —COOalkyl;
or
(3) —COOaryl;
R15 is
(1) hydrogen;
(2) alkyl;
(3) aryl;
(4) arylalkyl;
or
(5) cycloalkyl;
Z1, Z2 and Z3 are each independently
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aralkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (16) of the definition of Z1, Z2 and Z3;
(2) —OH or —OZ6;
(3) —SH or —SZ6;
(4) C(O)qH, C(O)qZ6, or —O—C(O)qZ6;
(5) —SO3H, —S(O)qZ6;
or S(O)qN(Z9)Z6;
(6) halo;
(7) cyano;
(8) nitro;
(9) -Z4-NZ7Z8;
(10) -Z4-N(Z9)-Z5-NZ7Z8;
(11) -Z4-N(Z10)-Z5-Z6;
(12) -Z4-N(Z10)-Z5-H;
(13) oxo;
(14) —O—C(O)-Z6;
(15) any two of Z1, Z2, and Z3 may together be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
or
(16) any two of Z1, Z2, and Z3 may together be —O—(CH2)r—O—, where r is 1 to 5, completing a 4- to 8-membered ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12-;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
or
(8) -Z11-C(O)—O-Z12-;
Z7, Z8, Z9 and Z10
(1) are each independently hydrogen or Z6;
(2) Z7 and Z8, or Z6 and Z10, may together be alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) Z7 or Z8, together with Z9, may be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with Z1, Z2 and Z3;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
and
Z13 is
(1) a single bond;
(2) -Z11-S(O)q-Z12-;
(3) -Z11-C(O)-Z12—;
(4) -Z11-C(S)-Z12-;
(5) -Z11-O-Z12-;
(6) -Z11-S-Z12-;
(7) -Z11-O—C(O)-Z12-;
(8) -Z11-C(O)—O-Z12-;
(9) —C(NR13)—;
(10) —C(CHR14)—;
or
(111) —C(C(R14)2)—
provided said compound is other than a compound of formula (vii)
where
R3e is pyridyl or pryimidinyl optionally substituted with halogen or alkyl;
R50 and R5, are each independently hydrogen, halogen or alkyl;
R52 and R53 are each independently hydrogen, halogen, alkyl or haloalkyl;
R54 and R56 are each independently hydrogen, halogen, alkyl, nitro or amino;
R55 is hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, or alkoxycarbonyl;
and
n is zero or 1.

121 more elements

Facts

Application

11/271,626Filed 10 Nov 2005

Priority

15 Apr 1999

Published

13 Apr 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification37 codes

C07D 277/56
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,…:…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 5/14
Drugs for disorders of the endocrine system: of the thyroid hormones, e.g. T3, T4
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

Family

Application60/129,510Us provisional application · filed 15 Apr 1999

Application09/548,929Continuation · filed 13 Apr 2000

Application10/378,373Continuation · filed 3 Mar 2003

Application11/271,626Continuation · filed 10 Nov 2005

US 2004/0077875 A1Published application

US 6,596,746 B1Related patent

US 8,716,323 B2Related patent

US 2006/0079563 A1This patent

From the US filing history. Foreign family members aren’t listed.