Naphthyridine derivatives as inhibitors of Hypoxia inducible factor (HIF) hydroxylase

A compound represented by Formula Ib:

• wherein
• q is 0 or 1;
• R1 is selected from the group consisting of hydrogen, cyano, halo, hydroxy, alkoxy, amino, acyloxy, aminoacyl, alkyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl;
• one of Z3 or Z4 is —NR2— and the other of Z3 or Z4 is —C(O)—;
• R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
• R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, amino, acyloxy, aminoacyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl;
• is a single or a double bond;
• Y is —NR6— or —O—;
• n is 1, 2, 3, 4, 5, or 6;
• R5 is selected from the group consisting of hydrogen, acyl, sulfonyl, aminoacyl, oxycarbonyl, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
• R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
• R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
• or R7 and R8 together with the carbon atom to which they are attached form a cycloalkyl, or heterocycloalkyl;
• W is selected from the group consisting of R9, —C(O)OR9, —C(O)NR6R9, —NR6C(O)R9, —NR6C(O)OR9, —NR6C(O)NR6R9, —NR6S(O)2R9, —S(O)2NR6R9, —NR6R9 and —OR9;
• and
• R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
• and
• further wherein each alkyl, alkoxy, amino, acyloxy, aminoacyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl described above for R1, R2, R3, R4, R6, R7, R8 and R9 can be optionally substituted with from 1 to 3 R10,
• wherein each R10 is independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, acyl, acylamino, acyloxy, amino, aminoacyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aryl, aryloxy, aryloxyaryl, cyano, halogen, hydroxyl, nitro, oxo, thioxo, carboxyl, carboxyl ester, cycloalkyl, thio, alkylthio, arylthio, cycloalkylthio, heteroarylthio, heterocyclicthio, sulfonyl, heteroaryl, heterocyclic, cycloalkoxy, heteroaryloxy, heterocyclyloxy, oxycarbonylamino, oxythiocarbonylamino, —OS(O)2-alkyl, —OS(O)2-aryl, —OS(O)2-heteroaryl, —OS(O)2-heterocyclic, —OSO2—NR40R40, —NR40S(O)2—NR40-alkyl, —NR40S(O)2—NR40-aryl, —NR40S(O)2—NR40-heteroaryl, and —NR40S(O)2—NR40-heterocyclic, where each R40 is independently selected from the group consisting of hydrogen or alkyl;
• and further wherein each alkyl, alkoxy, aryl, aryloxy, aryloxyaryl, cycloalkyl, alkylthio, arylthio, cycloalkylthio, heteroarylthio, heterocyclicthio, heteroaryl, heterocyclic, cycloalkoxy, heteroaryloxy, or heterocyclyloxy may be additionally substituted with from 1-3 substituents independently alkyl, alkoxy, haloalkyl, haloalkoxy, and halogen;
• or a pharmaceutically acceptable salt, single stereoisomer, mixture of stereoisomers, ester, tautomer or prodrug thereof.