US 7,071,193 B2Granted

7-amino-2-alkylthiopteridin-4-yl-amines for the treatment of chemokine-related diseases

AssigneeAstraZeneca AB

InventorsRoger Bonnert, Iain Walters

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Abstract

Pteridine compounds of formula (I) processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in the treatment of inflammatory diseases such as psoriasis, rheumatoid arthritis, diseases in which angiogenesis is assocated with raised CXCR2 chemokine levels (diabetic retinopathy) and COPD. The compounds are ligands for chemokine receptors and medical indications mentioned in the description include: diseases of the respiratory tract (COPDD, asthma, bronchitis, rhinitis, fibroid lung, pneumonia, etc.), diseases of the bones and joints (arthritis, etc.), skin-diseases (psoriasis, etc), diseases of the gastrointestinal tract, diseases in other tissues and systemic disease (multipe sclerosis, atherosclerosis, AIDS, type 1 diabetes, leprosy, sepsis, etc.), allograft rejection, cancers, cystic fibrosis, stroke, burn wounds, skin ulcers, reproductive disease and more.

Claims9

Dependent claims

A compound of formula (I) or a pharmaceutically acceptable salt thereof:

in which
R1 represents a C3–C7 carbocyclic, C1–C8 alkyl, C2–C6 alkenyl or C2–C6 alkynyl group, each of groups being optionally substituted by one or more substituent groups independently selected from halogen atoms, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9 or an aryl or heteroaryl group, both of which may be optionally substituted by one or more substituents independently selected from halogen atoms, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9, C1–C6 alkyl or trifluoromethyl groups;
one of R2 and R3 is hydrogen and the other is C1–C8 alkyl substituted by hydroxy and one or more methyl or ethyl groups,
R4 represents hydrogen, C1–C6 alkyl or a phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, —OR11 and —NR12R13
R5 and R6 independently represent a hydrogen atom or a C1–C6 alkyl or phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, —OR14 and —NR15R16, —CONR15R16, —NR15COR16, —SONR15R16, NR15SO2R16 or
R5 and R6 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring system optionally containing a further heteroatom selected from oxygen and nitrogen atoms, which ring system may be optionally substituted by one or more substituent groups independently selected from phenyl, —OR14, —COOR14, —NR15R16, —CONR15R16, —NR15COR16, —SONR15R16, NR15SO2R16 or C1–C6 alkyl, itself optionally substituted by one or more substituents independently selected from halogen atoms and —NR15R16 and —OR17 groups;
R10 represents a hydrogen atom or a C1–C6-alkyl or a phenyl group, the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, —OR17 and —NR15R16;
and
each of R7, R8, R9, R11, R12, R13, R14, R15, R16, R17 independently represents a hydrogen atom or a C1–C6, alkyl, or a phenyl group.

6 more elements

A compound of formula (II)

where R1 represents a C3–C7 carbocyclic, C1–C8 alkyl, C2–C6 alkenyl or C2–C6 alkynyl group, each of the groups being optionally substituted by one or more substituent groups independently selected from halogen atoms, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10, —SO2NR5R6, —NR8SO2R9 or an aryl or heteroaryl group, both of which may be optionally substituted by one or more substituents independently selected from halogen atoms, cyano, nitro, —OR4, —NR5R6, —CONR5R6, —COOR7, —NR8COR9, —SR10, —SO2R10 —SO2NR5R6, —NR8SO2R9, C1–C6 alkyl or trifluoromethyl groups
R4 represents hydrogen, C1–C6 alkyl or a phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, —OR11 and —NR12R13
R5 and R6 independently represent a hydrogen atom or a C1–C6 alkyl or phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, —OR14 and —NR15R16, —CONR15R16, —NR15COR16, —SONR15R16, NR15SO2R16 or
R5 and R6 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring system optionally containing a further heteroatom selected from oxygen and nitrogen atoms, which ring system may be optionally substituted by one or more substituent groups independently selected from phenyl, —OR4, —COOR14, —NR15R16, —CONR15R16, —NR15COR16, —SONR15R16, NR15SO2R16 or C1–C6 alkyl, itself optionally substituted by one or more substituents independently selected from halogen atoms and —NR15R16 and —OR17 groups;
R10 represents a hydrogen atom or a C1–C6-alkyl or a phenyl group, the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, —OR17 and —NR15R16;
and
each of R7, R8, R9, R11, R12, R13, R14, R15, R16, R17 independently represents a hydrogen atom or a C1–C6, alkyl, or a phenyl group.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/399,570Filed 16 Oct 2001
Priority: SE 000382820 Oct 2000
Published: US 2004/0102447 A127 May 2004
Granted: 4 Jul 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 475/06
Heterocyclic compounds containing pteridine ring systems: with a nitrogen atom directly attached in position 4
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 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 11/00
Drugs for disorders of the respiratory system