US 2009/0156554 A1Published application

P13-kinases

AssigneeBoehringer Ingelheim International GmbH

InventorsSteffen BREITFELDER, Udo MAIER, Trixi BRANDL, Christoph HOENKE, Matthias GRAUERT, Alexander PAUTSCH, Matthias HOFFMANN, Frank KALKBRENNER, Anne T. JOERGENSEN, Gerhard SCHAENZLE, Stefan PETERS, Frank BUETTNER, Eckhart BAUER

Life of this patent

Estimating the term…

patentgrep

Loading patent…

Abstract

New compounds of formula 1 are provided which by virtue of their pharmaceutical activity as PI3-kinase modulators may be used in the therapeutic field for the treatment of inflammatory or allergic diseases. Examples of these include inflammatory and allergic respiratory complaints, inflammatory diseases of the gastro-intestinal tract and motor apparatus, inflammatory and allergic skin diseases, inflammatory eye diseases, diseases of the nasal mucosa, inflammatory or allergic conditions involving autoimmune reactions or inflammations of the kidney.

Claims34

Dependent claims

A compound of formula 1;

with the proviso that the circular line designated A denotes an aromatic system;
wherein
Y denotes carbon, nitrogen atom, sulphur;
Z denotes carbon, nitrogen atom, sulphur;
j denotes 1, 2 or 3;
k denotes 0 or 1;
Ra denotes H, COR8, NR9R10, NO2, OR8, SR11, SOR11, SO2R11, NHCO—C1-6-alkyl-NH2, or a group selected from among C1-6-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C3-8-cycloalkenyl, C1-6-haloalkyl, aryl, C7-11-aralkyl, spiro, het, hetaryl and CH2—O-aryl, which may optionally be substituted;
R8 denotes C1-6-alkyl, C3-6-cycloalkyl, NH2, hetaryl or aryl, optionally substituted by one or more halogens or C1-4-alkyl;
R9 denotes H, COOR12, CONR12 or C1-6-alkyl, optionally substituted by one or more COOH, N(C1-6-alkyl)2 or het, optionally substituted by one or more C1-6-alkyl;
or R9 denotes het, optionally substituted by one or more C1-4-alkyl;
R10 denotes H, C1-6-alkyl, CO—C1-6-alkyl or C2-6-alkynyl;
R11 denotes C1-6-alkyl, optionally substituted by one or more N(C1-4-alkyl)2;
Rb denotes R4, OR4, —CH2OR4, COR4, COOR4, CONR4R5, NR4R5, NR5COR4, NR5COOR4, NR5CONR4R5, NR5SOR4 or NR5SO2R4;
R4, R5 denote H, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkylene-OH, C2-6-alkenyl, C7-11-aralkyl, C2-4-alkenyl-aryl, C2-4-alkynyl-aryl, C1-4-alkyl-hetaryl, C2-4-alkenyl-hetaryl, C2-4-alkynyl-hetaryl, C2-6-alkynyl, optionally substituted by Si(C1-4-alkyl)3, or R4 denotes a group selected from among aryl, het, hetaryl and optionally substituted by C1-4-alkyl;
or R4 and R5 together form a five-, six- or seven-membered ring consisting of carbon atoms and optionally a heteroatom selected from among oxygen, nitrogen and sulphur;
Rc denotes NHR6 or a group selected from among
wherein
B denotes a bond, C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl;
R6 denotes H or a group selected from among C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkenyl, het, aryl, hetaryl optionally substituted by one or more groups R6.1;
R6.1 denotes halogen, CF3, OH, CN, OMe, SO2(C1-4-alkyl);
R7 denotes H, C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, NR7.1R7.2, OR7.2, SR7.2, hetaryl, het, optionally substituted by C1-4-alkyl or CONH2;
R7.1 denotes H, C1-6-alkyl, (CH2)2-4R7.1.1 or COObutyl;
R7.2 denotes H, C1-6-alkyl, optionally substituted by one or more OH;
R7.1.1 denotes NR7.1.1.1R7.1.1.2, het or 1-imidazolyl, 2-(N-ethylpyrrolidine);
R7.1.1.1 denotes H or C1-6-alkyl;
R7.1.1.2 denotes H or C1-6-alkyl;
or a pharmacologically acceptable salt thereof, with the proviso that Ra cannot be H or Me if Y is nitrogen;
Z is nitrogen;
j is 2;
k is 0;
Rb is H and Rc is NHCONH-Et.

28 more elements

A compound of formula 1.1

wherein
Ra denotes H, COR8, NR9R10, NO2, OR8, SR11, SOR11, SO2R11, NHCO—C1-6-alkyl-NH2, or a group selected from among C1-6-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C3-8-cycloalkenyl, C1-6-haloalkyl, aryl, C7-11-aralkyl, spiro, het, hetaryl and CH2—O-aryl, which may optionally be substituted;
R8 denotes C1-6-alkyl, C3-6-cycloalkyl, NH2, hetaryl or aryl, optionally substituted by one or more halogens or C1-4-alkyl;
R9 denotes H, COOR12, CONR12 or C1-6-alkyl, optionally substituted by one or more COOH, N(C1-6-alkyl)2 or het, optionally substituted by one or more C1-6-alkyl;
or R9 denotes het, optionally substituted by one or more C1-4-alkyl;
R10 denotes H, C1-6-alkyl, CO—C1-6-alkyl or C2-6-alkynyl;
R11 denotes C1-6-alkyl, optionally substituted by one or more N(C1-4-alkyl)2;
Rb denotes R4, OR4, —CH2OR4, COR4, COOR4, CONR4R5, NR4R5, NR5COR4, NR5COOR4, NR5CONR4R5, NR5SOR4 or NR5SO2R4;
R4, R5 denote H, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkylene-OH, C2-6-alkenyl, C7-11-aralkyl, C2-4-alkenyl-aryl, C2-4-alkynyl-aryl, C1-4-alkyl-hetaryl, C2-4-alkenyl-hetaryl, C2-4-alkynyl-hetaryl, C2-6-alkynyl, optionally substituted by Si(C1-4-alkyl)3, or R4 denotes a group selected from among aryl, het, hetaryl and optionally substituted by C1-4-alkyl;
or R4 and R5 together form a five-, six- or seven-membered ring consisting of carbon atoms and optionally a heteroatom selected from among oxygen, nitrogen and sulphur;
Rc denotes NHR6 or a group selected from among
wherein
B denotes a bond, C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl;
R6 denotes H or a group selected from among C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkenyl, het, aryl, hetaryl optionally substituted by one or more groups R6.1;
R6.1 denotes halogen, CF3, OH, CN, OMe, SO2(C1-4-alkyl);
R7 denotes H, C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, NR7.1R7.2, OR7.2, SR7.2, hetaryl, het, optionally substituted by C1-4-alkyl or CONH2;
R7.1 denotes H, C1-6-alkyl, (CH2)2-4R7.1.1 or COObutyl;
R7.2 denotes H, C1-6-alkyl, optionally substituted by one or more OH;
R7.1.1 denotes NR7.1.1.1R7.1.1.2, het or 1-imidazolyl, 2-(N-ethylpyrrolidine);
R7.1.1.1 denotes H or C1-6-alkyl;
R7.1.1.2 denotes H or C1-6-alkyl;
or a pharmacologically acceptable salt thereof.

19 more elements

A compound of formula 1.2

wherein
Ra denotes H, COR8, NR9R10, NO2, OR8, SR11, SOR11, SO2R11, NHCO—C1-6-alkyl-NH2, or a group selected from among C1-6-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C3-8-cycloalkenyl, C1-6-haloalkyl, aryl, C7-11-aralkyl, spiro, het, hetaryl and CH2—O-aryl, which may optionally be substituted;
R8 denotes C1-6-alkyl, C3-6-cycloalkyl, NH2, hetaryl or aryl, optionally substituted by one or more halogens or C1-4-alkyl;
R9 denotes H, COOR12, CONR12 or C1-6-alkyl, optionally substituted by one or more COOH, N(C1-6-alkyl)2 or het, optionally substituted by one or more C1-6-alkyl;
or R9 denotes het, optionally substituted by one or more C1-4-alkyl;
R10 denotes H, C1-6-alkyl, CO—C1-6-alkyl or C2-6-alkynyl;
R11 denotes C1-6-alkyl, optionally substituted by one or more N(C1-4-alkyl)2;
Rb denotes R4, OR4, —CH2OR4, COR4, COOR4, CONR4R5, NR4R5, NR5COR4, NR5COOR4, NR5, CONR4R5, NR5SOR4 or NR5SO2R4;
R4, R5 denote H, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkylene-OH, C2-6-alkenyl, C7-11-aralkyl, C2-4-alkenyl-aryl, C2-4-alkynyl-aryl, C1-4-alkyl-hetaryl, C2-4-alkenyl-hetaryl, C2-4-alkynyl-hetaryl, C2-6-alkynyl, optionally substituted by Si(C1-4-alkyl)3, or R4 denotes a group selected from among aryl, het, hetaryl and optionally substituted by C1-4-alkyl;
or R4 and R5 together form a five-, six- or seven-membered ring consisting of carbon atoms and optionally a heteroatom selected from among oxygen, nitrogen and sulphur;
Rc denotes NHR6 or a group selected from among
wherein
B denotes a bond, C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl;
R6 denotes H or a group selected from among C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkenyl, het, aryl, hetaryl optionally substituted by one or more groups R6.1;
R6.1 denotes halogen, CF3, OH, CN, OMe, SO2(C1-4-alkyl);
R7 denotes H, C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, NR7.1R7.2, OR7.2, SR7.2, hetaryl, het, optionally substituted by C1-4-alkyl or CONH2;
R7.1 denotes H, C1-6-alkyl, (CH2)2-4R7.1.1 or COObutyl;
R7.2 denotes H, C1-6-alkyl, optionally substituted by one or more OH;
R7.1.1 denotes NR7.1.1.1R7.1.1.2, het or 1-imidazolyl, 2-(N-ethylpyrrolidine);
R7.1.1.1 denotes H or C1-6-alkyl;
R7.1.1.2 denotes H or C1-6-alkyl;
or a pharmacologically acceptable salt thereof

19 more elements

A compound of formula 1.3

wherein
Ra denotes H, COR8, NR9R10, NO2, OR8, SR11, SOR11, SO2R11, NHCO—C1-6-alkyl-NH2, or a group selected from among C1-6-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C3-8-cycloalkenyl, C1-6-haloalkyl, aryl, C7-11-aralkyl, spiro, het, hetaryl and CH2—O-aryl, which may optionally be substituted;
R8 denotes C1-6-alkyl, C3-6-cycloalkyl, NH2, hetaryl or aryl, optionally substituted by one or more halogens or C1-4-alkyl;
R9 denotes H, COOR12, CONR12 or C1-6-alkyl, optionally substituted by one or more COOH, N(C1-6-alkyl)2 or het, optionally substituted by one or more C1-6-alkyl;
or R9 denotes het, optionally substituted by one or more C1-4-alkyl;
R10 denotes H, C1-6-alkyl, CO—C1-6-alkyl or C2-6-alkynyl;
R11 denotes C1-6-alkyl, optionally substituted by one or more N(C1-4-alkyl)2;
Rb denotes R4, OR4, —CH2OR4, COR4, COOR4, CONR4R5, NR4R5, NR5COR4, NR5COOR4, NR5CONR4R5, NR5SOR4 or NR5SO2R4;
R4, R5 denote H, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkylene-OH, C2-6-alkenyl, C7-11-aralkyl, C2-4-alkenyl-aryl, C2-4-alkynyl-aryl, C1-4-alkyl-hetaryl, C2-4-alkenyl-hetaryl, C2-4-alkynyl-hetaryl, C2-6-alkynyl, optionally substituted by Si(C1-4-alkyl)3, or R4 denotes a group selected from among aryl, het, hetaryl and optionally substituted by C1-4-alkyl;
or R4 and R5 together form a five-, six- or seven-membered ring consisting of carbon atoms and optionally a heteroatom selected from among oxygen, nitrogen and sulphur;
Rc denotes NHR6 or a group selected from among
wherein
B denotes a bond, C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl;
R6 denotes H or a group selected from among C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkenyl, het, aryl, hetaryl optionally substituted by one or more groups R6.1;
R6.1 denotes halogen, CF3, OH, CN, OMe, SO2(C1-4-alkyl);
R7 denotes H, C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, NR7.1R7.2, OR7.2, SR7.2, hetaryl, het, optionally substituted by C1-4-alkyl or CONH2;
R7.1 denotes H, C1-6-alkyl, (CH2)2-4R7.1.1 or COObutyl;
R7.2 denotes H, C1-6-alkyl, optionally substituted by one or more OH;
R7.1.1 denotes NR7.1.1.1R7.1.1.2, het or 1-imidazolyl, 2-(N-ethylpyrrolidine);
R7.1.1.1 denotes H or C1-6-alkyl;
R7.1.1.2 denotes H or C1-6-alkyl;
or a pharmacologically acceptable salt thereof.

19 more elements

A compound of formula 1.4

wherein
Ra denotes H, COR8, NR9R10, NO2, OR8, SR11, SOR11, SO2R11, NHCO—C1-6-alkyl-NH2, or a group selected from among C1-6-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C3-8-cycloalkenyl, C1-6-haloalkyl, aryl, C7-11-aralkyl, spiro, het, hetaryl and CH2—O-aryl, which may optionally be substituted;
R8 denotes C1-6-alkyl, C3-6-cycloalkyl, NH2, hetaryl or aryl, optionally substituted by one or more halogens or C1-4-alkyl;
R9 denotes H, COOR12, CONR12 or C1-6-alkyl, optionally substituted by one or more COOH, N(C1-6-alkyl)2 or het, optionally substituted by one or more C1-6-alkyl;
or R9 denotes het, optionally substituted by one or more C1-4-alkyl;
R10 denotes H, C1-6-alkyl, CO—C1-6-alkyl or C2-6-alkynyl;
R11 denotes C1-6-alkyl, optionally substituted by one or more N(C1-4-alkyl)2;
Rb denotes R4, OR4, —CH2OR4, COR4, COOR4, CONR4R5, NR4R5, NR5COR4, NR5COOR4, NR5, CONR4R5, NR5SOR4 or NR5SO2R4;
R4, R5 denote H, C1-6-alkyl, C1-6-haloalkyl, C1-6-alkylene-OH, C2-6-alkenyl, C7-11-aralkyl, C2-4-alkenyl-aryl, C2-4-alkynyl-aryl, C1-4-alkyl-hetaryl, C2-4-alkenyl-hetaryl, C2-4-alkynyl-hetaryl, C2-6-alkynyl, optionally substituted by Si(C1-4-alkyl)3, or R4 denotes a group selected from among aryl, het, hetaryl and optionally substituted by C1-4-alkyl;
or R4 and R5 together form a five-, six- or seven-membered ring consisting of carbon atoms and optionally a heteroatom selected from among oxygen, nitrogen and sulphur;
Rc denotes NHR6 or a group selected from among
wherein
B denotes a bond, C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl;
R6 denotes H or a group selected from among C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkenyl, het, aryl, hetaryl optionally substituted by one or more groups R6.1;
R6.1 denotes halogen, CF3, OH, CN, OMe, SO2(C1-4-alkyl);
R7 denotes H, C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, NR7.1R7.2, OR7.2, SR7.2, hetaryl, het, optionally substituted by C1-4-alkyl or CONH2;
R7.1 denotes H, C1-6-alkyl, (CH2)2-4R7.1.1 or COObutyl;
R7.2 denotes H, C1-6-alkyl, optionally substituted by one or more OH;
R7.1.1 denotes NR7.1.1.1R7.1.1.2, het or 1-imidazolyl, 2-(N-ethylpyrrolidine);
R7.1.1.1 denotes H or C1-6-alkyl;
R7.1.1.2 denotes H or C1-6-alkyl;
or a pharmacologically acceptable salt thereof.

19 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/366,248Filed 5 Feb 2009
Priority: DE 10 2004 048 8777 Oct 2004
Published: 18 Jun 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification23 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 11/00
Drugs for disorders of the respiratory system

Family

Application11/244,299Continuation · filed 5 Oct 2005
Application12/366,248Continuation
US 2006/0106013 A1Published application
US 8,232,286 B2Related patent
US 2009/0156554 A1This patent

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