Fused ring compound containing furan or salt thereof and pharmaceutical composition comprising same

摘要

The present invention provides a fused ring compound containing furan or a pharmaceutically acceptable salt thereof, a method for preparing same, a pharmaceutical composition comprising same, and a use thereof. The fused ring compound containing furan or a pharmaceutically acceptable salt thereof inhibits the activity of phosphatidylinositol 3-kinase (PI3K) and can therefore be used in a pharmaceutical composition for treating and preventing respiratory diseases, inflammatory diseases, proliferative diseases, cardiovascular diseases, or central nervous system diseases which occur due to the over-activation of PI3K.

主权项

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein, A is hydrogen or —(CH2)mQ, B is hydrogen; —(C≡C)R1; —(CH2)mQ; —(CH═CH)(CH2)mQ; —(C≡C)(CH2)mQ; —NH(CH2)pQ; —(CONH)(CH2)mQ; or —CONR1R2, wherein, one of A and B is hydrogen, and A and B cannot be hydrogen at the same time, m is an integer from 0 to 3, p is an integer from 0 to 3, Q is phenyl; pyridyl; pyrazolyl; thiophenyl; pyrimidinyl; thiazolyl; pyridazinyl; piperazinyl; morpholinyl; piperidinyl; tetrahydropyridyl; naphthyl; benzothiophenyl; benzodioxolyl; dihydrobenzofuranyl; dihydrobenzoxazinyl; benzodioxinyl; benzothiadiazolyl; quinolyl; indazolyl; benzoimidazolyl; dihydrobenzodioxinyl; benzothiazolyl; or indolyl, wherein Q is optionally substituted with one or more substituents selected from the group consisting of hydroxy; amino; halogen; cyano; C1-C10alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, cyano, C1-C6alkoxy and C1-C6alkylcarbonyloxy; C2-C10alkenyl; 4-oxo-2-thioxothiazolidin-5-ylidenyl; C2-C10alkynyl; C3-C10cycloalkyl; 5- to 7-membered heterocycloalkyl-C1-C4alkyl, wherein, said heterocycloalkyl is optionally substituted with C1-C4alkyl; C6-C12aryl; 5- to 12-membered heteroaryl optionally substituted with C1-C4alkyl; 3- to 12-membered heterocycloalkyl optionally substituted with C1-C6alkyl; C1-C10alkoxy optionally substituted with one or more substituents selected from halogen and cyano; C3-C10cycloalkyloxy; C6-C12aryl-C1-C10alkyloxy, wherein, said aryl is optionally substituted with C1-C3alkoxy; C6-C12aryloxy optionally substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, hydroxycarbonyl, cyano and nitro; 5- to 12-membered heteroaryloxy optionally substituted with one or more substituents selected from the group consisting of hydroxy, amino, halogen, hydroxycarbonyl, cyano and nitro; C1-C10alkylcarbonyloxy; C1-C10alkylthio; mono- or di-C1-C10alkylamino; mono- or di-C3-C7cycloalkylamino; C6-C12arylamino; 5- to 12-membered heteroarylamino; C1-C10alkylsulfonylamino; C6-C12arylsulfonylamino; 5- to 12-membered heteroarylsulfonylamino; C1-C10alkylcarbonylamino; C6-C12arylcarbonylamino; 5- to 12-membered heteroarylcarbonylamino; formyl; C1-C10alkylcarbonyl; C6-C12arylcarbonyl; 5- to 12-membered heteroarylcarbonyl; C1-C10alkoxycarbonyl; hydroxycarbonyl; C6-C12aryloxycarbonyl; 5- to 12-membered heteroaryloxycarbonyl; aminocarbonyl; mono- or di-C1-C10alkylaminocarbonyl, wherein said alkyl is optionally substituted with hydroxy; C6-C12arylaminocarbonyl; 5- to 12-membered heteroarylaminocarbonyl; aminosulfonyl; mono- or di-C1-C10alkylaminosulfonyl, wherein, said alkyl is optionally substituted with hydroxy; C3-C7cycloalkylaminosulfonyl; C1-C10alkylsulfonyl optionally substituted with hydroxy; 5- to 7-membered heterocycloalkyl-sulfonyl, wherein, said heterocycloalkyl is optionally substituted with C1-C4alkyl; C6-C12arylaminosulfonyl; 5- to 12-membered heteroarylaminosulfonyl; C1-C10alkylsulfinyl; C1-C10alkylcarbamoyloxy; and C1-C10alkylureido, R1 and R2 are each independently hydrogen; C1-C10alkyl optionally substituted with one or more substituents selected from hydroxy and C1-C6alkoxy; C3-C10cycloalkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, C1-C6alkoxy and C1-C6alkylcarbonyloxy; C1-C10alkoxycarbonyl; C1-C10alkylcarbonyl; or R1 and R2 join together to form a 5- to 12-membered ring optionally containing a heteroatom selected from N and O, R is a substituent selected from the group consisting of the following chemical formulae, * indicates the binding site in which the compound of formula (I) is connected to, D is NR7, O or S, E is O or S, R3 is hydrogen; or C1-C10alkyl optionally substituted with hydroxy, R4 is 3- to 12-membered heterocycloalkyl (said heterocycloalkyl is optionally substituted with C1-C10alkyl or halogen); C1-C10alkoxy; C1-C10alkylthio; or NR8R9, R6 is hydrogen or C1-C10alkyl, R7 is hydrogen or C1-C10alkyl, R8 and R9 are each independently hydrogen; C1-C6alkyl optionally substituted with one or more substituents selected from C1-C6alkoxycarbonyl and C6-C12aryl, wherein said aryl is optionally substituted with halogen or C1-C6alkoxy; C6-C12aryl optionally substituted with one or more substituents selected from the group consisting of halogen, C1-C6alkyl and C1-C6alkoxy; or 5- to 12-membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of halogen, C1-C6alkyl and C1-C6alkoxy.