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US 7,745,646 B2Granted
Bicyclic heteroaryl inhibitors of PDE4
AssigneeKalypsys, Inc.
InventorsSteven Govek, Andrew K. Shiau, Stewart A. Noble, David J. Thomas
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds and methods which may be useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of inflammatory diseases and other diseases involving elevated levels of cytokines and proinflammatory mediators.
Claims22
A compound of structural Formula IV
- or a salt thereof, wherein:
- R1 and R2 are independently selected from the group consisting of —(CH2)sG1G2G3, acyl, acylalkyl, carboxyalkyl, cyanoalkyl, alkoxy, alkoxyalkyl, amidoalkyl, amino, alkyl, alkylalkoxy, aminoalkyl, alkenyl, alkynyl, carboxyl, carboxyalkyl, ether, heteroalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aralkyl, aryl, guanidine, heteroaryl, heteroaralkyl, and hydroxyalkyl, any of which may be optionally substituted;
- s is 0-8;
- G1 is selected from the group consisting of alkoxy, amino, amido, carbonyl, hydroxy, ether, an amino acid, and null;
- G2 is selected from the group consisting of alkyl, alkoxy, amino, aryl, halo, haloalkyl, heterocycloalkyl, heteroaryl, carboxylalkylamino, guanidine, an amino acid, and null, any of which may be optionally substituted;
- G3 is selected from the group consisting of alkyl, alkoxy, amino, hydroxy, ether, carboxyl, hydroxamic acid, an amino acid, phosphonate, phosphoamide, and null, any of which may be optionally substituted;
- when s is 0, G1, G2, and G3 may not all together be null;
- R3 and R4 are independently selected from the group consisting of alkoxy, lower alkyl, halogen and hydrogen;
- R5 is selected from the group consisting of (CH2)p, C(O)NH, N(R7) and S(O)q;
- p is 1,2,3 or 4;
- q is 0, 1 or 2;
- R6 is selected from the group consisting of aryl heteroaryl, either of which may be optionally substituted;
- R7 selected from the group consisting of hydrogen and optionally substituted lower alkyl;
- R17 is selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, amino, aminoalkyl and aminoalkoxy.
11 more elements
A compound of structural Formula VI
- or a salt thereof, wherein:
- R1 and R2 are independently selected from the group consisting of —(CH2)sG1G2G3, acyl, acylalkyl, carboxyalkyl, cyanoalkyl, alkoxy, alkoxyalkyl, amidoalkyl, amino, alkyl, alkylalkoxy, aminoalkyl, alkenyl, alkynyl, carboxyl, carboxyalkyl, ether, heteroalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aralkyl, aryl, guanidine, heteroaryl, heteroaralkyl and hydroxyalkyl, any of which may be optionally substituted;
- s is 1-8;
- G1 is selected from the group consisting of alkoxy, acyl, amino, amido, carbonyl, ether, an amino acid, and null;
- G2 is selected from the group consisting of alkyl, alkoxy, acyl, amino, aryl, halo, haloalkyl, heterocycloalkyl, heteroaryl, carboxylalkylamino, guanidine, an amino acid, and null, any of which may be optionally substituted;
- G3 is selected from the group consisting of alkyl, alkoxy, amino, hydroxy, ether, carboxyl, hydroxamic acid, an amino acid, phosphonate, phosphoamide, and null, any of which may be optionally substituted;and
- R19 and R23 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, amino, and carboxyl.
4 more elements
A compound of structural Formula VII
- or a salt thereof, wherein:
- R1 and R2 are independently selected from the group consisting of —(CH2)sG1G2G3, acyl, acylalkyl, carboxyalkyl, cyanoalkyl, alkoxy, alkoxyalkyl, amidoalkyl, amino, alkyl, alkylalkoxy, aminoalkyl, alkenyl, alkynyl, carboxyl, carboxyalkyl, ether, heteroalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aralkyl, aryl, guanidine, heteroaryl, heteroaralkyl and hydroxyalkyl, any of which may be optionally substituted;
- s is 1-8;
- G1 is selected from the group consisting of alkoxy, acyl, amino, amido, carbonyl, ether, an amino acid, and null;
- G2 is selected from the group consisting of alkyl, alkoxy, acyl, amino, aryl, halo, haloalkyl, heterocycloalkyl, heteroaryl, carboxylalkylamino, guanidine, an amino acid, and null, any of which may be optionally substituted;
- G3 is selected from the group consisting of alkyl, alkoxy, amino, hydroxy, ether, carboxyl, hydroxamic acid, an amino acid, phosphonate, phosphoamide, and null, any of which may be optionally substituted;
- and
- R19, R21, and R23 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, amino, and carboxyl.
5 more elements
A compound selected from the group consisting of Examples 1 to 105.
Dependencies are inferred from the claim text.