3H-PYRAZOLO[4.3:f] QUINOLINE-BASED COMPOUNDS AS STING ANTAGONISTS

A compound of formula (IA):

• wherein
• R2 is selected from H, alkyl, heteroalkyl, aryl, heteroaryl, alkenyl, alkynyl, and halogen;
• R4 is selected from H, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, and amide, wherein the amide is selected from sulfonamide, benzamide, nicotinamide, picolinamide and a derivative of any of the forgoing;
• and R4 is optionally substituted with OH, OR2, halogen, CF3, CN, NRR′, CONRR′, SO2R2, SO2NRR′, NCOR2 or NSO2R2, wherein each R and R′ is independently selected from H, halogen, CF3, CN, alkyl, aryl, heteroalkyl, heteroaryl, CONR2R2, COR2, SO2R2, (C═O)NR2, (C═NH)R2, (C═O)OR2, C6H5R2, morpholine and piperazine, wherein R2 is as defined above;
• or
• R and R′, together with the atom to which they are attached, form a 4- to 6-membered cyclic or heterocyclic ring;
• R5 is selected from H, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, and amide, wherein the amide is selected from sulfonamide, benzamide, nicotinamide, picolinamide and a derivative of any of the forgoing;
• and R5 is optionally substituted with OH, OR2, halogen, CF3, CN, NRR′, CONRR′, SO2R2, SO2NRR′, NCOR2 or NSO2R2, wherein R2, R and R′ are as defined above;
• and with the proviso that R5 is not H, methyl, CF3, CH2—CH2—OH, CH2—CH2—C1, COOH, or optionally substituted phenyl, wherein the substitution on phenyl is OMe, COOMe, or amino;
• R4 and R5 can be the same or different;
• and
• each X is independently selected from O, S, SO, SO2, CRR′, CNRR′, COR′, NR′ and Xn, wherein n is 0-2;
• wherein each R and R′ is independently selected from H, halogen, CF3, CN, alkyl, aryl, heteroalkyl, heteroaryl, CONR2R2, COR2, SO2R2, (C═O)NR2, (C═NH)R2, (C═O)OR2, C6H5R2, morpholine and piperazine, wherein R2 is as defined above;
• or
• R and R′, together with the atom to which they are attached, form a 4- to 6-membered cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salt, hydrate, tautomer, or optical isomer thereof.

A compound of formula (IB):

• wherein
• R2 is selected from H, alkyl, heteroalkyl, aryl, heteroaryl, alkenyl, alkynyl, and halogen;
• R3 is selected from H, alkyl, heteroalkyl, aryl, heteroaryl, alkenyl, and alkynyl;
• each X is independently selected from O, S, SO, SO2, CRR′, CNRR′, COR′, NR′ and Xn, wherein n is 0-2;
• wherein each R and R′ is independently selected from H, halogen, CF3, CN, alkyl, aryl, heteroalkyl, heteroaryl, CONR2R2, COR2, SO2R2, (C═O)NR2, (C═NH)R2, (C═O)OR2, C6H5R2, morpholine and piperazine, wherein R2 is as defined above;
• or
• R and R′, together with the atom to which they are attached, form a 4- to 6-membered cyclic or heterocyclic ring;
• Y is N or CR2, wherein R2 is as defined above;
• n is 0 or 1;
• Q is selected from NR″, CR2R2, N(COR2), N(SO2)R2, N(C═O)NR2, N(C═NH)R2, and N(C═O)OR2, with the proviso that when Q is NR″, R″ is not H, methyl, isopropyl, CH2CH2OH, COCH3 or SO2-methyl;
• and when Q is CR2R2, R2 is not H or dimethyl amine;
• or a pharmaceutically acceptable salt, hydrate, tautomer, or optical isomer thereof.