| CPC C07D 471/04 (2013.01) [A61P 7/00 (2018.01); C07D 491/20 (2013.01)] | 22 Claims |
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1. A method of treating a disease associated with hypoxia inducible factors, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I,
 or an isotopically labeled compound thereof, or an optical isomer thereof, a geometric isomer thereof, a tautomer thereof or a mixture of various isomers, or a pharmaceutically acceptable salt thereof, or a prodrug thereof
in which
R1 and R2 are each independently selected from the group consisting of cyano, alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, acyl, amino, R9O—, R9S—, R9(O═)S—, and R9(O═)2S—, wherein R9 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl or heteroaryl; and wherein the alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, acyl, and amino are optionally substituted by one or more substituents wherein the substituents are independently selected from the group consisting of halo, cyano, hydroxy, amino, carboxy, acyl, alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, ═O, ═S, —SH, R10O—, R10S—, R10(O═)S—, and R10(O═)2S—, and wherein R10 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl, or heteroaryl; or R1 and R2 are taken together to form a ring;
R3, R4 and R5 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, carboxy, cyano, amino, acyl, alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, R11O—, R11S—, R11 (O═)S—, and R11 (O═)2S—, wherein R11 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl or heteroaryl; wherein the alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, acyl, and amino are optionally substituted by one or more substituents wherein the substituents are independently selected from the group consisting of halogen, cyano, hydroxy, amino, carboxy, acyl, alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, ═O, ═S, —SH, R12O—, R12S—, R12(O═)S—, and R12(O═)2S—, and wherein R12 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl, or heteroaryl;
R6 and R6′ are each independently selected from the group consisting of hydrogen and optionally substituted alkyl;
R7 is selected from the group consisting of hydrogen, alkyl and acyl; wherein the alkyl and acyl are optionally substituted by the following groups: halogen, cyano, hydroxy, amino, carboxy, acyl, alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, ═O, ═S, —SH, R13O—, R13S—, R13(O═)S—, and/or R13(O═)2S—, wherein R13 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl, or heteroaryl;
R8 is selected from the group consisting of hydrogen, alkyl and —OC(O)R14, wherein R14 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl or heteroaryl; wherein the alkyl, heterocyclyl, alkenyl, alkynyl, aryl, or heteroaryl group is optionally substituted with the following groups: halogen, cyano, hydroxy, amino, carboxy, acyl, alkyl, heterocyclyl, alkenyl, alkynyl, aryl, heteroaryl, ═O, ═S, —SH, R15O—, R15S—, R15(O═)S—, and/or R15(O═)2S—; wherein R15 is alkyl, heterocyclyl, alkenyl, alkynyl, aryl, or heteroaryl; and
X is an oxygen atom or a sulfur atom or NH,
wherein the disease associated with hypoxia-inducing factors is selected from the group consisting of anemia, cardiovascular disease, neurological diseases, HIV infections, rheumatoid arthritis, surgery-related ischemia, fetal suffocation, cancer and diseases associated with cancer, eye diseases, central nervous system diseases, chronic kidney disease, renal insufficiency and acute renal failure, sexual dysfunction, diabetes and its complications selected from diabetic macroangiopathy and microangiopathy, diabetic nephropathy, neurodegenerative diseases, ischemic diseases and fibrotic diseases.
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