Fused-ring compounds, pharmaceutical composition and uses thereof

A compound of formula (I), an isomer, a prodrug, a stable isotope derivative or a pharmaceutically acceptable salt thereof;

• Wherein,
• n is 1, 2 or 3;
• t is 1 or 2;
• U is N, C, or CR4, bond α is a single or double bond;
• when U is N or CR4, bond α is a single bond;
• when U is C, bond α is a double bond;
• A ring is 5-membered heteroaromatic ring;
• Z, Z1, Z2, Z3, Z4 are independently N or C, and Z3 and Z4 are not N at the same time;
• B ring is benzene or a 5- or 6-membered heteroaromatic ring;
• When bond α is a single bond, A1 is —(CR9R9a)m— or —C2-4 alkenyl-;
• When bond α is a double bond, A1 is —CR9(CR9R9a)m—;
• R9 is independently hydrogen, halogen, substituted or unsubstituted alkyl,
• substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclolalkyl, substituted or unsubstituted alkoxy, wherein the substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, or substituted alkoxy is alkyl, cycloalkyl, heterocycloalkyl, or alkoxy substituted by one or more substituent(s) at any position independently selected from halogen, hydroxyl, alkyl, heterocycloalkyl, cycloalkyl, alkoxy, amino, aryl, heteroaryl, —SR6, —NR6R6a, —S(O)2NR6R6a, —NR8C(O)NR6R6a, —NR6C(O)R6a, —NR6S(O)2R6a, —C(O)R6, —S(O)0-2R6, —C(O)OR6, —C(O)NR6R6a, —(CH2)rOH, and —(CH2)rNR6R6a;
• R9a is independently hydrogen, deuterium, halogen, substituted or unsubstituted alkyl;
• or R9 and R9a together with the carbon atom to which they are attached form a 3- to 8-membered mono-cycloalkyl ring, wherein the substituted alkyl is alkyl substituted by one or more substituent(s) at any position independently selected from hydroxyl, halogen, and C3-6 cycloalkyl;
• A2 is —C(═R7)(CR5R5a)m—, —(CR5R5a)m—, —(C═R7)O—, —(CR5R5a)mO—, or —S(O)0-2(CR5R5a)m—;
• R5 and R5a are independently hydrogen, hydroxyl, halogen, alkyl, amino, —SR6, —OR6, —NR6R6a, —NR6S(O)2R6a, —S(O)2NR6R6a, —(CH2)rS(O)0-2CH3, —OS(O)3H, —OP(O)(O—R6)2, —OC(O)R6, —OC(O)NR6R6a, —C(O)NR6R6a, —(CH2)rC(O)OH, —(CH2)rOH, —(CH2)rC(O)NR6R6a, or —(CH2)rNR6R6a;
• R1 is hydrogen, halogen, hydroxyl, alkyl, alkoxy, alkylthiol, haloalkyl, haloalkoxy, amino, C2-6alkynyl, C2-6alkenyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, —SH, —CN, —NO2, —OC(O)R6, —OC(O)OR6, —OC(O)NR6R6a, —C(O)OR6, —C(O)R6, —C(O)NR6R6a, —NR6R6a, —NR6C(O)R6a, —NR6C(O)OR6a, —NR6C(O)NR6R6a, —(CH2)rNR6R6a, —NR6S(O)2R6a, —S(O)0-2R6, or —S(O)2NR6R6a;
• R2 is hydrogen, halogen, hydroxyl, alkyl, alkoxy, alkylthiol, haloalkyl, haloalkoxy, amino, C2-6 alkynyl, C2-6 alkenyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, —SH, —CN, —NO2, or —NR6R6a;
• R3 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted bridged tricycloalkyl, or substituted or unsubstituted bridged heterocycloalkyl;
• provided that when U is C or CR4 and B ring is benzene, R3 is substituted or unsubstituted bridged tricycloalkyl, or substituted or unsubstituted bridged heterocycloalkyl, wherein the substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted bridged tricycloalkyl, or substituted bridged heterocycloalkyl is substituted by one or more R10;
• R4 is hydrogen, deuterium, halogen, —CN, —C(O)OH, tetrazole, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, wherein the substituted alkyl, substituted alkoxy is substituted at any position by one or more R12 which is independently selected from halogen, hydroxyl, alkyl, bridged tricycloalkyl, alkoxy, aryl, heteroaryl, amino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, —SR6, —NR6R6a, —S(O)2NR6R6a, —NR6C(O)NR6R6a, —C(O)R6, —S(O)0-2R6, —C(O)OR6, —(CH2)rOH, and —(CH2)rNR6R6a, further wherein the substituted cycloalkyl, or substituted heterocycloalkyl is substituted by one or more of substituent(s) independently selected from hydroxyl, amino, and halogen;
• R10 is independently -L-C(R8)═R10a, —NO2, —CN, —OH, —NH2, —SH, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted bridged tricycloalkyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted C2-6 alkenyl, —C2-6 alkynyl-R8b, -L-R8, —O-L-R8, —S(O)0-2-L-R8, —N(R8)-L-R8b, -L-OR8b, -L-OC(O)R8b, -L-OC(O)NR8R8b, -L-OC(O)OR8b, -L-OP(O)(O—R8)2, -L-B(O—R8)2, -L-OS(O)2(OH), -L-OS(O)1-2R8b, -L-S(O)1-2OR8b, -L-S(O)2NR8R8b, -L-S(O)0-2R8b, -L-S(O)2N(R8)C(O)NR8R8b, -L-C(O)OR8b, -L-C(O)R8b, -L-C(O)N(OH)R8b, -L-C(═R7)NR8R8b, -L-NR8R8b, -L-N(R8)C(O)OR8b, -L-N(R8)C(═R7)R8b, -L-N(R8)C(O)N(R8)S(O)2R8b, -L-N(R8)OR8b, -L-N(R8)C(═R7)NR8R8b, -L-N(R8)S(O)1-2R8b, -L-N(R8)S(O)1-2NR8R8b, or R8 and R8b together with the nitrogen atom to which they are attached, form a 3- to 8-membered mono-heterocycloalkyl ring;
• wherein the substituted alkyl, substituted alkoxy, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted cycloalkylalkyl, substituted heterocycloalkylalkyl, substituted arylalkyl, substituted heteroarylalkyl, substituted bridged tricycloalkyl, substituted C2-6 alkenyl, or substituted C2-6 alkynyl, is substituted by 1 to 3 R13 at any position;
• R13 is —OH, —SH, —CN, —NO2, —NH2, halogen, alkylthiol, —C(═R7)NR6R6a, —OC(O)R6, —OC(O)OR6, —OC(O)NR6R6a, —C(O)OR6, —C(O)R6, —C(O)NR6R6a, —NR6R6a, —NR6C(O)R6a, —NR6C(═R7)R6a, —NR6C(O)OR6a, —NR6C(O)NR6R6a, —NR6C(═R7)NR6R6a, —(CH2)rNR6R6a, —NR6S(O)2R6a, —NR6S(O)2NR6R6a, —S(O)0-2R6, —S(O)2NR6R6a, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• wherein the substituted alkyl, substituted alkoxy, substituted C2-6 alkenyl, substituted C2-6 alkynyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl, or substituted heterocycloalkyl is substituted at any position by 1 to 3 substituent(s) independently selected from C1-3 alkyl, halogen, C1-3 alkoxy, halo-C1-3 alkoxy, hydroxyl, and amino;
• is selected from ═O, ═S, ═N(R8b), ═N(OR8b), ═C(R8b)2, ═C(R8b)(OR8b), and ═C(R8b)(NHR8b);
• L is a bond or L1, wherein L1 is —(CR8R8a)r;
• or R8 and R8a together with the carbon atom to which they are attached, form a 3- to 8-membered mono-cycloalkyl ring;
• R8 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, one-end modified or unmodified polyethylene glycol, monosaccharide, disaccharide, amino acid, peptide with 3-20 amino acid residues, or
• R8a is selected from hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted arylalkyl, and substituted or unsubstituted heteroarylalkyl;
• R8b is selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, -L1-R8, -L1-OR8, -L1-N(R8)2, -L1-C(O)OR8, -L1-OC(O)R8, -L1-C(O)N(R8)2, -L1-N(R8)C(O)R8, -L1-N(R8)C(O)N(R8)2, -L1-N(R8)C(S)N(R8)2, -L1-OS(O)1-2R8, -L1-S(O)1-2OR8, -L1-S(O)0-2R8, -L1-N(R8)S(O)2N(R8)2, -L1-S(O)2N(R8)2, -L1-N(R8)S(O)2R8, -L1-N(R8)C(O)N(R8)S(O)2R8, and -L1-OP(O)(O—R8)2;
• further wherein the substituted alkyl, substituted alkoxy, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted cycloalkylalkyl, substituted heterocycloalkylalkyl, substituted arylalkyl, or substituted heteroarylalkyl in R8, R8a or R8b is substituted at any position by 1 to 3 R14 group independently selected from —OH, —SH, —CN, —NO2, —NH2, halogen, alkylthiol, —C(═R7)NR6R6a, —OC(O)R6, —OC(O)OR6, —OC(O)NR6R6a, —C(O)OR6, —C(O)R6, —C(O)NR6R6a, —NR6R6a, —NR6C(O)R6a, —NR6C(═R7)R6a, —NR6C(O)OR6a, —NR6C(O)NR6R6a, —NR6C(═R7)NR6R6a, —(CH2)rNR6R6a, —NR6S(O)2R6a, —NR6S(O)2NR6R6a, —S(O)0-2R6, —S(O)2NR6R6a, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, and substituted or unsubstituted heteroaryl, wherein the substituted alkyl, substituted alkoxy, substituted C2-6 alkenyl, substituted C2-6 alkynyl, or substituted aryl, substituted heteroaryl, substituted cycloalkyl, or substituted heterocycloalkyl in R14 group is substituted at any position by 1 to 3 substituent(s) independently selected from C1-3 alkyl, halogen, C1-3 alkoxy, halo-C1-3 alkoxy, hydroxyl, and amino;
• is independently ═O, ═S, ═N(R6), or ═N(OR6);
• R6 and R6a is independently hydrogen, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, heterocycloalkylalkyl, cycloalkylalkyl, arylalkyl, or heteroarylalkyl, or R6 and R6a together with the nitrogen atom to which they are attached, form a 3- to 8-membered mono-heterocycloalkyl ring;
• r is an integer ranging from 1 to 8;
• and
• m is 0, 1, 2, or 3.