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US 7,022,686 B2Granted
A1 adenosine receptro antagonists
AssigneeBiogen Idec Inc.
InventorsKo-Chung Lin, Chi Vu
Life of this patent
Estimating the term…
Abstract
Compounds of Formula I and II are disclosed as antagonists of subtype A1 adenosine receptors. These compounds are useful for treatment of various diseases and disorders, including systemic hypertension, renal failure, diabetes, asthma, an edematous condition, congestive heart failure, and renal dysfunction.
Claims22
A compound of formula I:
- or a pharmacogically acceptable addition salt thereof,
- wherein R1 and R2 are independently selected from the group consisting of:
- a) hydrogen;
- b) alkyl, alkenyl or alkynyl, wherein said alkyl, alkenyl, or alkynyl is either unsubstituted or functionalized with one or more substituents selected from the group consisting of hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl, acylamino, alkylsulfonylamino, and heterocyclylcarbonylamino;
- and
- c) aryl or substituted aryl;
- R3 is a bicyclic, tricyclic or pentacyclic group selected from the group consisting of:
- wherein the bicyclic, tricyclic or pentacyclic group is functionalized with one or more substituents selected from the group consisting of:
- (i) alkyl, alkenyl and alkynyl;
- wherein each alkyl, alkenyl or alkynyl group is functionalized with one or more substituents selected from the group consisting of aminoalkylcarbamoyl, -aminocycloalkylcarbamoyl, oxo, cyanoalkylcarbamoyl, phosphono, R5-alkylcarbamoyl;
- and
- (ii) aminoalkylcarbamoyl, aminocycloalkylcarbamoyl, oxo, cyanoalkylcarbamoyl, phosphono, R5-alkylcarbamoyl;
- R4 is selected from the group consisting of hydrogen, C1-4-alkyl, C1-4-alkyl-CO2H, and phenyl, wherein the C1-4-alkyl, C1-4-alkyl-CO2H, and phenyl groups are either unsubstituted or functionalized with one to three substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, NO2, benzyl, and benzyl functionalized with one to three substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, and —NO2;
- R5 is selected from the group consisting of —(CR1R2)nCOOH, —C(CF3)2OH, —CONHNHSO2CF3, —CONHOR4, —CONHSO2R4, —CONHSO2NHR4, —C(OH)R4PO3H2, —NHCOCF3, —NHCONHSO2R4, —NHPO3H2, —NHSO2R4, —NHSO2NHCOR4, —OPO3H2, —OSO3H, —PO(OH)R4, —PO3H2, —SO3H, —SO2NHR4, —SO3NHCOR4, —SO3NHCONHCO2R4, and the following:
- n=0, 1, 2 or 3;
- A is selected from the group consisting of —CH═CH, —(CH2)m—(CH2)m, —CH═CH—CH2, and —CH2—CH═CH;
- each m is independently selected from 1 or 2;
- X is O or S;
- Z is selected from the group consisting of a single bond, —O—, —(CH2)n—, —O(CH2)1-2—, —CH2OCH2—, —(CH2)1-2O—, and
- R6 is selected from the group consisting of hydrogen, alkyl, acyl, alkylsulfonyl, aralkyl, substituted aralkyl, substituted alkyl, and heterocyclyl;
- and
- R7 is selected from the group consisting of:
- a) hydrogen;
- b) alkyl, alkenyl of not less than 3 carbons, or alkynyl of not less than 3 carbons;
- wherein said alkyl, alkenyl or alkynyl is either unsubstituted or functionalized with one or more substituents selected from the group consisting of hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl, acylamino, alkylsulfonylamino, and heterocyclylcarbonylamino;
- and
- c) aryl or substituted aryl
- d) alkylaryl or alkyl substituted aryl.
25 more elements
A compound of formula II:
- or a pharmacologically acceptable addition salt thereof,
- wherein R1 and R2 are independently selected from the group consisting of:
- a) hydrogen;
- b) alkyl, alkenyl or alkynyl, wherein said alkyl, alkenyl, or alkynyl is either unsubstituted or functionalized with one or more substituents selected from the group consisting of hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl, acylamino, alkylsulfonylamino, and heterocyclylcarbonylamino;
- and
- c) aryl or substituted aryl;
- R3 is a bicyclic, tricyclic or pentacyclic group selected from the group consisting of:
- wherein the bicyclic, tricyclic or pentacyclic group is functionalized with one or more substituents selected from the group consisting of:
- (i) alkyl, alkenyl and alkynyl;
- wherein each alkyl, alkenyl or alkynyl group is functionalized with one or more substituents selected from the group consisting of aminoalkylcarbamoyl, aminocycloalkylcarbamoyl, oxo, cyanoalkylcarbamoyl, phosphono, R5-alkylcarbamoyl,;
- and
- (ii) aminoalkylcarbamoyl, aminocycloalkylcarbamoyl, oxo, cyanoalkylcarbamoyl, phosphono, R5-alkylcarbamoyl;
- R4 is selected from the group consisting of hydrogen, C1-4-alkyl, C1-4-alkyl-CO2H, and phenyl, wherein the C1-4-alkyl, C1-4-alkyl-CO2H, and phenyl groups are either unsubstituted or functionalized with one to three substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, NO2, benzyl, and benzyl functionalized with one to three substituents selected from the group consisting of halogen, —OH, —OMe, —NH2, and —NO2;
- R5 is selected from the group consisting of —(CR1R2)nCOOH, —C(CF3)2OH, —CONHNHSO2CF3, —CONHOR4, —CONHSO2R4, —CONHSO2NHR4, —C(OH)R4PO3H2, —NHCOCF3, —NHCONHSO2R4, —NHPO3H2, —NHSO2R4, —NHSO2NHCOR4, —OPO3H2, —OSO3H, —PO(OH)R4, —PO3H2, —SO3H, —SO2NHR4, —SO3NHCOR4, —SO3NHCONHCO2R4, and the following:
- n=0, 1, 2 or 3;
- A is selected from the group consisting of —CH═CH, —(CH2)m—(CH2)m, —CH═CH—CH2, and —CH2—CH═CH;
- each m is independently selected from 1 or 2;
- X is O or S;
- Z is selected from the group consisting of a single bond, —O—, —(CH2)n—, —O(CH2)1-2—, —CH2OCH2—, and —(CH2)1-2O—,
- R6 is selected from the group consisting of hydrogen, alkyl, acyl, alkylsulfonyl, aralkyl, substituted aralkyl, substituted alkyl, and heterocyclyl;
- and
- R7 is selected from the group consisting of:
- a) hydrogen;
- b) alkyl, alkenyl of not less than 3 carbons, or alkynyl of not less than 3 carbons;
- wherein said alkyl, alkenyl or alkynyl is either unsubstituted or functionalized with one or more substituents selected from the group consisting of hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl, acylamino, alkylsulfonylamino, and heterocyclylcarbonylamino;
- and
- c) aryl or substituted aryl
- d) alkylaryl or alkyl substituted aryl.
25 more elements
Dependencies are inferred from the claim text.