Novel benzoxazine benzimidazole derivative, a pharmaceutical composition comprising the same, and ause thereof

A compound of formula (1) or a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof:

• wherein,
• R1 is hydrogen or (CRaRa′)mRb, Ra and Ra′ being each independently hydrogen;
• C1˜C8 alkyl;
• C2˜C8 alkenyl;
• halogen;
• nitro;
• hydroxy;
• cyano;
• azido;
• amino;
• phenyl;
• benzyl;
• C1˜C8 alkoxy;
• C1˜C6 alkylamino;
• or substituted C1˜C6 alkyl, phenyl or benzyl having one or more Rc groups;
• and Rb being hydrogen;
• hydroxy;
• or substituted C1˜C6 alkyl, phenyl or benzyl having one or more Rc groups;
• in which Rc is halogen;
• cyano;
• nitro;
• azido;
• phenyl;
• benzyl;
• C(═O)Rd;
• C(═O)ORd;
• C(═O)NRdRd;
• ORd;
• OC(═O)Re;
• OC(═O)ORe;
• OC(═O)NRdRd;
• OC1 ˜C6alkylORd;
• OC1˜C6alkylNRdRd;
• SRd;
• S(═O)Re;
• S(═O)2Re;
• S(═O)2NRdRd. CRd═NRd;
• NRdRd;
• NRdC(═O)Re;
• NRdC(═O)ORe;
• NRdC(═O)NRdRd;
• NRdC(═NRd)NRdRd;
• NRdS(═O)2Re;
• NRdORd;
• NRdC1˜C6alkylNRdRd;
• or NRdC1˜C6alkylORd;
• in which Rd is hydrogen or Re;
• Re being phenyl;
• benzyl;
• C1˜C6 alkyl;
• phosphoryl;
• or substituted phenyl, benzyl or C1˜C6 alkyl having one or more hydroxy, halogen, C1˜C4 alkyl, C1˜C3 haloalkyl, C1˜C4 alkoxy, amino, C1˜C4 alkylamino or di(C1˜C4 alkyl)amino groups;
• and m is 0, 1, or 2;
• R2 is hydrogen;
• C1˜C8 alkyl;
• C2˜C6 alkenyl;
• C1˜C8 alkoxy;
• C1˜C6 haloalkyl;
• C1˜C6 haloalkoxy;
• halogen;
• nitro;
• hydroxy;
• C1˜C6 hydroxyalkyl;
• cyano;
• amino;
• amido;
• substituted amino or amido having one or two C1˜C6 alkyl, C2˜C6 alkenyl, C1˜C8 alkoxy, C1˜C6 haloalkyl, C1˜C6 haloalkoxy, halogen, nitro, hydroxy, or cyano groups;
• non-substituted or substituted cycloalkyl, pyridinyl, pyrimidinyl, pyrazolyl, pyrazinyl, phenyl, benzyl, imidazolyl, morpholinyl, benzodioxolyl, benzothiazolyl, benzimidazolyl, indolyl, pyrazolonyl, thiophenyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, oxodiazolyl, thiadiazolyl, indazolyl, pyrrolidinyl, chromonyl, piperidinyl, morpholmethyl, dihydropyrazolyl or (CH2)pU having one, two or three sulfonamido groups, in which p is 0, 1, or 2;
• and U is morpholinyl,
• R14, R15 and R16 are independently hydrogen;
• C1˜C8 alkyl;
• cycloalkyl;
• C2˜C6 alkenyl;
• C1˜C6 alkoxy;
• C1˜C6 haloalkyl;
• C1˜C6 haloalkoxy;
• halogen;
• nitro;
• hydroxy;
• C1˜C6 hydroxyalkyl;
• cyano;
• sulfanyl;
• sulfonyl;
• sulfinyl;
• sulfonamido;
• urea;
• carbamate;
• carbonate;
• carbonyl;
• amino;
• amido;
• carboxyl;
• carboxylester;
• substituted amino, amido, carboxyl or carboxylester having one or two C1˜C3 alkyl groups;
• or any two of R14, R15 and R16 being fused together to form a saturated or unsaturated heteromonocyclic or heterobicyclic ring;
• R3 and R3′ are independently hydrogen;
• C1˜C10 alkyl;
• C2˜C10 alkenyl;
• C2˜C10 alkynyl;
• C3˜C10 cycloalkyl;
• C8˜C14 bicycloalkyl;
• C3˜C10 cycloalkenyl;
• C8˜C14 bicycloalkenyl;
• C3˜C7 heterocycloalkyl;
• C7˜C10 heterobicycloalkyl;
• C1˜C6 hydroxyalkyl;
• C1˜C8 alkoxy;
• C1˜C6 haloalkyl;
• C1˜C6 haloalkoxy;
• halogen;
• nitro;
• hydroxy;
• cyano;
• azido;
• amino;
• substituted C1˜C6 hydroxyalkyl, C1˜C10 alkyl, C2˜C10 alkenyl, C2˜C10 alkynyl, C3˜C10 cycloalkyl, C8˜C14 bicycloalkyl, C3˜C10 cycloalkenyl, C8˜C14 bicycloalkenyl, C3˜C7 heterocycloalkyl or C7˜C10 heterobicycloalkyl having one or more Rf substituents;
• phenyl;
• naphtyl;
• benzyl;
• C5˜C10 heteroaryl;
• or substituted phenyl, naphtyl, benzyl or C5˜C10 heteroaryl having one or more Rf substituents;
• wherein
• Q1 is N or CR4;
• Q2 is N or CR5;
• Q3 is N or CR6;
• Q4 is N or CR7;
• R4, R5, R6, and R7 are independently hydrogen;
• C1˜C10 alkyl;
• C2˜C10 alkenyl;
• C2˜C10 alkynyl;
• C3˜C10 cycloalkyl;
• C8˜C14 bicycloalkyl;
• C3˜C10 cycloalkenyl;
• C8˜C14 bicycloalkenyl;
• C3˜C7 heterocycloalkyl;
• C7˜C10 heterobicycloalkyl;
• C1˜C8 alkoxy;
• C1˜C6 haloalkyl;
• C1˜C6 haloalkoxy;
• halogen;
• nitro;
• hydroxy;
• cyano;
• azido;
• amino;
• substituted C3˜C10 alkyl, C2˜C10 alkenyl, C2˜C10 alkynyl, C3˜C10 cycloalkyl, C8˜C14 bicycloalkyl, C3˜C10 cycloalkenyl, C8˜C14 bicycloalkenyl, C3˜C7 heterocycloalkyl or C7˜C10 heterobicycloalkyl having one or more Rh groups;
• phenyl;
• naphtyl;
• benzyl;
• C5˜C10 heteroaryl;
• substituted phenyl, naphtyl, benzyl or C5˜C10 heteroaryl having one or more Rh substituents;
• C(═O)Ri;
• C(═O)ORi;
• C(═O)NRiRi;
• ORi;
• OC(═O)Rj;
• OC(═O)ORj;
• OC(═O)NRiRi;
• OC1˜C6alkylORi;
• OC1˜C6alkylNRiRi;
• SRi;
• S(═O)Rj;
• S(═O)2Rj;
• S(═O)2NRiRi;
• CRi═NRi;
• NRiRi;
• NRiC(═O)Rj;
• NRiC(═O)ORj;
• NRiC(═O)NRiRi;
• NRiC(═NRi)NRiRi;
• NRiS(═O)2Rj;
• NRiORi;
• NRiC1˜C6alkylNRiRi;
• or NRiC1˜C6alkylORi;
• or any two of R4, R5, R6 and R7 are fused together to form a saturated, partially saturated or unsaturated 5-, 6- or 7-membered heteromonocyclic ring or a saturated, partially saturated, or unsaturated 6-, 7-, 8-, 9-, 10- or 11-membered heterobicyclic ring which is optionally mono-, di-, tri- or tetra-substituted with a nitrogen, an oxygen or a sulfur groups;
• in which Rf and Rh are each independently C1˜C6 alkyl;
• C2-C6 alkenyl;
• C2˜C6 alkynyl;
• C3˜C8 cycloalkyl;
• C5˜C8 cycloalkenyl;
• C3˜C5 heterocycloalkyl;
• C1˜C6 haloalkyl;
• C1˜C6 haloalkoxy;
• halogen;
• azido;
• nitro;
• cyano;
• phenyl;
• benzyl;
• C(═O)Ri;
• C(═O)ORi, C(═O)NRiRi;
• ORi;
• OC(═O)Rj;
• OC(═O)ORj;
• OC(═O)NRiRi;
• OC1˜C6alkylORi;
• OC1˜C6alkylNRiRi;
• SRi;
• S(═O)Rj;
• S(═O)2Rj;
• S(═O)2NRiRi;
• CRi═NRi;
• NRiRi;
• NRiC(═O)Rj;
• NRiC(═O)ORj;
• NRdC(═O)NRiRi;
• NRiC(═NRi)NRiRi;
• NRiS(═O)2Rj;
• NRiORi;
• NRiC1˜C6alkylNRiRi;
• or NRiC1˜C6alkylORi;
• and Ri is hydrogen or Rj;
• Rj being phenyl;
• benzyl;
• C1˜C6 alkyl;
• C2˜C6 alkenyl;
• C2˜C6 alkynyl;
• C3˜C8 cycloalkyl;
• C5˜C8 cycloalkenyl;
• C3˜C5 heterocycloalkyl;
• phosphoryl;
• or substituted phenyl, benzyl or C1˜C6 alkyl having one or more hydroxy, halogen, C1˜C4 alkyl, C1˜C3 haloalkyl, C1˜C4 alkoxy, amino, C1˜C4 alkylamino or di(C1˜C4 alkyl)amino groups.