1, 4-oxazepane derivatives and uses thereof

A compound of formula (I), a stereoisomer thereof, an atropisomer, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a pharmaceutically acceptable salt of the atropisomer, a prodrug thereof, a deuterated molecule thereof or a conjugated form thereof:

• Wherein,
• X is selected from N or CR53;
• RS1 at each occurrence is independently selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, —N(R61)2, —OR61, —SR61, —S(═O)R62, —S(═O)2R62, —C(═O)R62, —C(═O)OR61, —OC(═O)R62, —C(═O)N(R61)2, —NR61C(═O)R62, —OC(═O)OR61, —NR61C(═O)OR61, —OC(═O)N(R61)2, —NR61C(═O)N(R61)2, —S(═O)OR61, —OS(═O)R62, —S(═O)N(R61)2, —NR61S(═O)R62, —S(═O)2OR61, —OS(═O)2R62, —S(═O)2N(R61)2, —NR61S(═O)2R62, —OS(═O)2OR61, —NR61S(═O)2OR61, —OS(═O)2N(R61)2, —NR61S(═O)2N(R61)2, —P(R61)2, —P(═O)(R62)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein, said —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more substituents selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, —N(R61)2, —OR61, —SR61, —S(═O)R62, —S(═O)2R62, —C(═O)R62, —C(═O)OR61, —OC(═O)R62, —C(═O)N(R61)2, —NR61C(═O)R62, —OC(═O)OR61, —NR61C(═O)OR61, —OC(═O)N(R61)2, —NR61C(═O)N(R61)2, —S(═O)OR61, —OS(═O)R62, —S(═O)N(R61)2, —NR61S(═O)R62, —S(═O)2OR61, —OS(═O)2R62, —S(═O)2N(R61)2, —NR61S(═O)2R62, —OS(═O)2OR61, —NR61S(═O)2OR61, —OS(═O)2N(R61)2, —NR61S(═O)2N(R61)2, —P(R61)2, —P(═O)(R62)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• Optionally, two RS1 together with the carbon atom to which they are both attached form
• a 3-20 membered carbocyclic ring or a 3-20 heterocyclic ring;
• wherein, said 3-20 membered carbocylic ring or 3-20 heterocyclic ring is optionally substituted with one or more R16a;
• Optionally, two adjacent RS1 together with the carbon atoms to which they are respectively attached form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aryl ring or a 5-10 membered heteroaryl ring, wherein, each of rings is independently optionally substituted with one or more R16b;
• Optionally, two nonadjacent RS1 are connected together to form a C0-6 alkylene bridge, wherein, each of the carbon atoms in the bridge is optionally replaced by 1 or 2 heteroatoms selected from N, O, S, S═O or S(═O)2;
• the hydrogen on the each of carbon atoms or N atoms is optionally independently substituted with R16c;
• q1 is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• R2 is selected from -L5-(3-12 membered heterocyclyl), -L5-(3-12 membered cycloalkyl), -L5-(6-12 member aryl), -L5-(5-12 membered heteroaryl), -L5-N(R75)2,
• Each of L5 at each occurrence is independently selected from a bond or C1-10 alkylene optionally substituted with one or more R16n;
• Said 3-12 membered heterocyclyl in -L5-(3-12 membered heterocyclyl) is optionally substituted with one or more R16o;
• Said 3-12 membered cycloalkyl in -L5-(3-12 membered cycloalkyl) is optionally substituted with one or more R16o;
• Said 6-12 member aryl in -L5-(6-12 member aryl) is optionally substituted with one or more R16o;
• Said 5-12 membered heteroaryl in -L5-(5-12 membered heteroaryl) is optionally substituted with one or more R16o;
• L7 is selected from a bond or C1-10 alkylene optionally substituted with one or more R16q;
• L8 is selected from a bond or C1-10 alkylene optionally substituted with one or more R16r;
• Ring E is selected from a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring;
• wherein the moiety of -L7- and -L5-X6 are attached to the same atom or different atoms of the ring E;
• X6 is selected from —N(R65)2, —OR65, —SR65, 3-10 membered heterocyclyl, or 5-10 membered heteroaryl, wherein said 3-10 membered heterocyclyl or 5-10 membered heteroaryl is optionally independently substituted with one or more R16a;
• Y is selected from a bond, —C(R63)2—, —R63C═CR63—, —C≡C—, —C(═O)—, —O—, —NR63—, —S—, —S(═O)—, —S(═O)2—, —PR63—, —P(═O)R64—, —C(═O)O—, —OC(═O)—, —C(═O)NR63—, —NR63C(═O)—, —S(═O)O—, —OS(═O)—, —S(═O)2O—, —OS(═O)2—, —S(═O)NR63—, —NR63S(═O)—, —S(═O)2NR63—, —NR63S(═O)2—, —OC(═O)O—, —NR63C(═O)O—, —OC(═O)NR63— or —NR63C(═O)NR63—;
• L1 is selected from a bond, —C(R65)2—, —R65C═CR65—, —C≡C—, —C(═O)—, —O—, —NR65—, —S—, —S(═O)—, —S(═O)2—, —PR65—, —P(═O)R66—, —C(═O)O—, —OC(═O)—, —C(═O)NR65—, —NR65C(═O)—, —S(═O)O—, —OS(═O)—, —S(═O)2O—, —OS(═O)2—, —S(═O)NR65—, —NR65S(═O)—, —S(═O)2NR65—, —NR65S(═O)2—, —OC(═O)O—, —NR65C(═O)O—, —OC(═O)NR65— or —NR65C(═O)NR65—;
• t is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• Ring A or ring B is a 3-20 membered heterocyclic ring which is optionally further contains 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ring members selected from —N—, —O—, —S—, —C(═O)—, —S(═O)—, —S(═O)2—, —S(═O)O—, —OS(═O)—, —S(═O)2O—, —OS(═O)2—, —S(═O)NH—, —NHS(═O)—, —S(═O)2NH—, —NHS(═O)2—;
• or a 3-20 membered heteroaryl ring which is optionally further contains 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ring members, selected from —N—, —O— or —S—;
• Each of RS2 at each occurrence is independently selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, oxo, —N(R67)2, —OR67, —SR67, —S(═O)R68, —S(═O)2R68, —C(═O)R68, —C(═O)OR67, —OC(═O)R68, —C(═O)N(R67)2, —NR67C(═O)R68, —OC(═O)OR67, —NR67C(═O)OR67, —NR67C(═S)OR67, —OC(═O)N(R67)2, —NR67C(═O)N(R67)2, —S(═O)OR67, —OS(═O)R67, —S(═O)N(R67)2, —NR67S(═O)R68, —S(═O)2OR67, —OS(═O)2R68, —S(═O)2N(R67)2, —NR67S(═O)2R68, —OS(═O)2OR67, —NR67S(═O)2OR67, —OS(═O)2N(R67)2, —NR67S(═O)2N(R67)2, —P(R67)2, —P(═O)(R68)2,
• 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein said —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more substituents selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, oxo, —N(R67)2, —OR62, —SR67, —S(═O)R68, —S(═O)2R68, —C(═O)R68, —C(═O)OR67, —OC(═O)R68, —C(═O)N(R67)2, —NR67C(═O)R68, —OC(═O)OR67, —NR67C(═O)OR67, —NR67C(═S)OR67, —OC(═O)N(R67)2, —NR67C(═O)N(R67)2, —S(═O)OR67, —OS(═O)R67, —S(═O)N(R67)2, —NR67S(═O)R68, —S(═O)2OR67, —OS(═O)2R68, —S(═O)2N(R67)2, —NR67S(═O)2R68, —OS(═O)2OR67, —NR67S(═O)2OR67, —OS(═O)2N(R67)2, —NR67S(═O)2N(R67)2, —P(R67)2, —P(═O)(R68)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• Optionally, two RS2 together with the carbon atom to which they are both attached form
• a 3-10 membered carbocyclic ring or a 3-10 heterocyclic ring;
• wherein, sais 3-10 membered carbocyclic ring or 3-10 heterocyclic ring is optionally substituted with one or more R16d;
• Optionally, two adjacent RS2 together with the carbon atoms to which they are respectively attached form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aryl ring or a 5-10 membered heteroaryl ring, wherein, each of rings is independently optionally substituted with one or more R16e;
• Optionally, two nonadjacent RS2 are connected together to form a C0-6 alkylene bridge, wherein, each of the carbon atoms in the bridge is optionally replaced by 1 or 2 heteroatoms selected from N, O, S, S═O or S(═O)2;
• the hydrogen on the each of carbon atoms or N atoms is optionally independently substituted with R16f;
• q2 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• Each of RS6 at each occurrence is independently selected from halogen, —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, haloC2-6alkenyl, —C2-6alkynyl, haloC2-6alkynyl, —CN, —NO2, —N3, oxo, —N(R73)2, —OR73, —SR73, —S(═O)R74, —S(═O)2R74, —C(═O)R74, —C(═O)OR73, —OC(═O)R74, —C(═O)N(R73)2, —NR73C(═O)R74, —OC(═O)OR73, —NR73C(═O)OR73, —OC(═O)N(R73)2, —NR73C(═O)N(R73)2, —S(═O)OR73, —OS(═O)R74, —S(═O)N(R73)2, —NR73S(═O)R74, —S(═O)2OR73, —OS(═O)2R74, —S(═O)2N(R73)2, —NR73S(═O)2R74, —OS(═O)2OR73, —NR73S(═O)2OR73, —OS(═O)2N(R73)2, —NR73S(═O)2N(R73)2, —P(R73)2, —P(═O)(R74)2, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein said —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, haloC2-6alkenyl, —C2-6alkynyl, haloC2-6alkynyl, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more substituents selected from halogen, —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, haloC2-6alkenyl, —C2-6alkynyl, haloC2-6alkynyl, —CN, —NO2, —N3, oxo, —N(R73)2, —OR73, —SR73, —S(═O)R74, —S(═O)2R73, —C(═O)R74, —C(═O)OR73, —OC(═O)R74, —C(═O)N(R73)2, —NR73C(═O)R74, —OC(═O)OR73, —NR73C(═O)OR73, —OC(═O)N(R73)2, —NR73C(═O)N(R73)2, —S(═O)OR73, —OS(═O)R74, —S(═O)N(R73)2, —NR73S(═O)R74, —S(═O)2OR73, —OS(═O)2R74, —S(═O)2N(R73)2, —NR73S(═O)2R74, —OS(═O)2OR73, —NR73S(═O)2OR74, —OS(═O)2N(R73)2, —NR73S(═O)2N(R73)2, —P(R73)2, —P(═O)(R74)2, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• q6 is selected from 0, 1, 2, 3, 4, 5 or 6;
• R4 is selected from 6-20 membered aryl, 5-20 membered heteroaryl
• wherein said 6-20 membered aryl, 5-20 membered heteroaryl,
• is optionally independently substituted with one or more R41;
• Z at each occurrence is independently selected from C or N;
• Ring C at each occurrence is independently selected from a 6 membered aryl ring or a 5-6 membered heteroaryl ring and ring D at each occurrence is a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring when Z is selected from C;
• Ring C at each occurrence is selected from a 5-6 membered heteroaryl ring and ring D at each occurrence is a 3-10 membered heterocyclic ring when Z is selected from N;
• R41 at each occurrence is independently selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, oxo, —N(R69)2, —OR69, —SR69, —S(═O)R70, —S(═O)2R70, —C(═O)R70, —C(═O)OR69, —OC(═O)R70, —C(═O)N(R69)2, —NR69C(═O)R70, —OC(═O)OR69, —NR69C(═O)OR69, —OC(═O)N(R69)2, —NR69C(═O)N(R69)2, —S(═O)OR69, —OS(═O)R70, —S(═O)N(R69)2, —NR69S(═O)R70, —S(═O)2OR69, —OS(═O)2R70, —S(═O)2N(R69)2, —NR69S(═O)2R70, —OS(═O)2OR69, —NR69S(═O)2OR69, —OS(═O)2N(R69)2, —NR69S(═O)2N(R69)2, —P(R69)2, —P(═O)(R70)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein said —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more substituents selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, oxo, —N(R69)2, —OR69, —SR69, —S(═O)R70, —S(═O)2R70, —C(═O)R70, —C(═O)OR69, —OC(═O)R70, —C(═O)N(R69)2, —NR69C(═O)R70, —OC(═O)OR69, —NR69C(═O)OR69, —OC(═O)N(R69)2, —NR69C(═O)N(R69)2, —S(═O)OR69, —OS(═O)R70, —S(═O)N(R69)2, —NR69S(═O)R70, —S(═O)2OR69, —OS(═O)2R70, —S(═O)2N(R69)2, —NR69S(═O)2R70, —OS(═O)2OR69, —NR69S(═O)2OR69, —OS(═O)2N(R69)2, —NR69S(═O)2N(R69)2, —P(R69)2, —P(═O)(R70)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• Each of (R51, R52 and R53) is independently selected from hydrogen, halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, —N(R71)2, —OR71, —SR71, —S(═O)R72, —S(═O)2R72, —C(═O)R72, —C(═O)OR71, —OC(═O)R72, —C(═O)N(R71)2, —NR71C(═O)R72, —OC(═O)OR71, —NR71C(═O)OR71, —OC(═O)N(R71)2, —NR71C(═O)N(R71)2, —S(═O)OR71, —OS(═O)R72, —S(═O)N(R71)2, —NR71S(═O)R72, —S(═O)2OR71, —OS(═O)2R72, —S(═O)2N(R71)2, —NR71S(═O)2R72, —OS(═O)2OR71, —NR71S(═O)2OR71, —OS(═O)2N(R71)2, —NR71S(═O)2N(R71)2, —P(R71)2, —P(═O)(R72)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein said —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more substituents selected from halogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, haloC2-10alkenyl, —C2-10alkynyl, haloC2-10alkynyl, —CN, —NO2, —N3, oxo, —N(R71)2, —OR71, —SR71, —S(═O)R72, —S(═O)2R72, —C(═O)R72, —C(═O)OR71, —OC(═O)R72, —C(═O)N(R71)2, —NR71C(═O)R72, —OC(═O)OR71, —NR71C(═O)OR71, —OC(═O)N(R71)2, —NR71C(═O)N(R71)2, —S(═O)OR71, —OS(═O)R72, —S(═O)N(R71)2, —NR71S(═O)R72, —S(═O)2OR71, —OS(═O)2R72, —S(═O)2N(R71)2, —NR71S(═O)2R72, —OS(═O)2OR71, —NR71S(═O)2OR71, —OS(═O)2N(R71)2, —NR71S(═O)2N(R71)2, —P(R71)2, —P(═O)(R72)2, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• Each of (R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R75, R80, R81, R82, R83, and R84) at each occurrence is independently selected from hydrogen, —C1-10alkyl, haloC1-10alkyl, haloC1-10alkoxy, —C2-10alkenyl, —C2-10alkynyl, —CN, —NO2, —N3, oxo, —N(Ra)2, —ORa, —SRa, —S(═O)Rb, —S(═O)2Rb, —C(═O)Rb, —C(═O)ORa, —OC(═O)Rb, —C(═O)N(Ra)2, —NRaC(═O)Rb, —OC(═O)ORa, —NRcC(═O)ORa, —OC(═O)N(Ra)2, —NRaC(═O)N(Ra)2, —S(═O)ORa, —OS(═O)Rb, —S(═O)N(Ra)2, —NRaS(═O)Rb, —S(═O)2ORa, —OS(═O)2Rb, —S(═O)2N(Ra)2, —NRaS(═O)2Rb, —OS(═O)2ORa, —NRaS(═O)2ORa, —OS(═O)2NRa, —NRaS(═O)2N(Ra)2, —P(Ra)2, —P(═O)(Rb)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein said —C1-10alkyl, haloC1-10alkyl, —C2-10alkenyl, —C2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more substituents selected from halogen, —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, —C2-6alkynyl, —CN, —NO2, —N3, oxo, —N(Rc)2, —ORc, —SR, —S(═O)Rd, —S(═O)2Rd, —C(═O)Rd, —C(═O)ORc, —OC(═O)Rd, —C(═O)N(Rc)2, —NRcC(═O)Rd, —OC(═O)ORc, —NRcC(═O)ORd, —OC(═O)N(Rc)2, —NRcC(═O)N(Rc)2, —S(═O)ORc, —OS(═O)Rd, —S(═O)N(Rc)2, —NRcS(═O)Rd, —S(═O)2ORc, —OS(═O)2Rd, —S(═O)2N(Rc)2, —NRcS(═O)2Rd, —OS(═O)2ORc, —NRcS(═O)2ORc, —OS(═O)2NRc, —NRcS(═O)2N(Rc)2, —P(Rc)2, —P(═O)(Rd)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• Optionally, each of (two R61, two R62, two R69, two R71, two R73, two R75, two Ra and two Rc) independently together with the nitrogen atom to which they are both attached forms a 3-20 membered heterocyclic ring or a 5-10 membered heteroaryl ring, wherein, said 3-20 membered heterocyclic ring or 5-10 membered heteroaryl ring is optionally independently substituted with one or more R16g;
• Optionally, each of (two R63 and two R65) independently together with the carbon atom to which they are both or independently attached forms a 3-20 membered carbocyclic ring or 3-20 membered heterocyclic ring, wherein, said 3-20 membered carbocyclic ring or 3-20 membered heterocyclic ring is optionally independently substituted with one or more R16h;
• Each of (Ra, Rb, Rc and Rd) at each occurrence is independently selected from hydrogen, —C1-6alkyl, haloC1-6 alkyl, haloC1-6alkoxy, —C2-6alkenyl, —C2-6alkynyl, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein said —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, —C2-6alkynyl, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally independently substituted with one or more R16i;
• Each of (R16a, R16b, R16c, R16d, R16e, R16f, R16g, R16h, R16i, R16n, R16o, R16q, R16r and R16s) at each occurrence is independently selected from halogen, —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, —C2-6alkynyl, —CN, —NO2, —N3, oxo, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —OH, —O(C1-6alkyl), —SH, —S(C1-6alkyl), —S(═O)(C1-6 alkyl), —S(═O)2(C1-6alkyl), —C(═O)(C1-6alkyl), —C(═O)OH, —C(═O)(OC1-6alkyl), —OC(═O)(C1-6alkyl), —C(═O)NH2, —C(═O)NH(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —NHC(═O)(C1-6alkyl), —N(C1-6alkyl)C(═O)(C1-6alkyl), —OC(═O)O(C1-6alkyl), —NHC(═O)(OC1-6alkyl), —N(C1-6alkyl)C(═O)(OC1-6alkyl), —OC(═O)NH(C1-6alkyl), —OC(═O)N(C1-6alkyl)2, —NHC(═O)NH2, —NHC(═O)NH(C1-6alkyl), —NHC(═O)N(C1-6alkyl)2, —N(C1-6alkyl)C(═O)NH2, —N(C1-6alkyl)C(═O)NH(C1-6alkyl), —N(C1-6alkyl)C(═O)N(C1-6alkyl)2, —S(═O)(OC1-6alkyl), —OS(═O)(C1-6alkyl), —S(═O)NH2, —S(═O)NH(C1-6alkyl), —S(═O)N(C1-6alkyl)2, —NHS(═O)(C1-6alkyl), —N(C1-6alkyl)S(═O)(C1-6alkyl), —S(═O)2(OC1-6alkyl), —OS(═O)2(C1-6alkyl), —S(═O)2NH2, —S(═O)2NH(C1-6alkyl), —S(═O)2N(C1-6alkyl)2, —NHS(═O)2(C1-6alkyl), —N(C1-6alkyl)S(═O)2(C1-6alkyl), —OS(═O)2O(C1-6alkyl), —NHS(═O)2O(C1-6alkyl), —N(C1-6alkyl)S(═O)2O(C1-6alkyl), —OS(═O)2NH2, —OS(═O)2NH(C1-6alkyl), —OS(═O)2N(C1-6alkyl)2, —NHS(═O)2NH2, —NHS(═O)2NH(C1-6alkyl), —NHS(═O)2N(C1-6alkyl)2, —N(C1-6alkyl)S(═O)2NH2, —N(C1-6alkyl)S(═O)2NH(C1-6alkyl), —N(C1-6alkyl)S(═O)2N(C1-6alkyl)2, —PH(C1-6alkyl), —P(C1-6alkyl)2, —P(═O)H(C1-6alkyl), —P(═O)(C1-6alkyl)2, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
• wherein, said —C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, —C2-6alkenyl, —C2-6alkynyl, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl is optionally substituted with one or more substituents selected from halogen, —C1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, —C2-3alkenyl, —C2-3alkynyl, —CN, —NO2, —N3, oxo, —NH2, —NH(C1-3alkyl), —N(C1-3 alkyl)2, —OH, —O(C1-3alkyl), —SH, —S(C1-3alkyl), —S(═O)(C1-3alkyl), —S(═O)2(C1-3alkyl), —C(═O)(C1-3alkyl), —C(═O)OH, —C(═O)(OC1-3alkyl), —OC(═O)(C1-3alkyl), —C(═O)NH2, —C(═O)NH(C1-3alkyl), —C(═O)N(C1-3alkyl)2, —NHC(═O)(C1-3alkyl), —N(C1-3alkyl)C(═O)(C1-3alkyl), —OC(═O)O(C1-3alkyl), —NHC(═O)(OC1-3alkyl), —N(C1-3alkyl)C(═O)(OC1-3alkyl), —OC(═O)NH(C1-3alkyl), —OC(═O)N(C1-3alkyl)2, —NHC(═O)NH2, —NHC(═O)NH(C1-3alkyl), —NHC(═O)N(C1-3alkyl)2, —N(C1-3alkyl)C(═O)NH2, —N(C1-3alkyl)C(═O)NH(C1-3alkyl), —N(C1-3alkyl)C(═O)N(C1-3alkyl)2, —S(═O)(OC1-3alkyl), —OS(═O)(C1-3alkyl), —S(═O)NH2, —S(═O)NH(C1-3alkyl), —S(═O)N(C1-3alkyl)2, —NHS(═O)(C1-3alkyl), —N(C1-3alkyl)S(═O)(C1-3alkyl), —S(═O)2(OC1-3alkyl), —OS(═O)2(C1-3alkyl), —S(═O)2NH2, —S(═O)2NH(C1-3alkyl), —S(═O)2N(C1-3alkyl)2, —NHS(═O)2(C1-3alkyl), —N(C1-3alkyl)S(═O)2(C1-3alkyl), —OS(═O)2O(C1-3alkyl), —NHS(═O)2O(C1-3alkyl), —N(C1-3alkyl)S(═O)2O(C1-3alkyl), —OS(═O)2NH2, —OS(═O)2NH(C1-3alkyl), —OS(═O)2N(C1-3alkyl)2, —NHS(═O)2NH2, —NHS(═O)2NH(C1-3alkyl), —NHS(═O)2N(C1-3alkyl)2, —N(C1-3alkyl)S(═O)2NH2, —N(C1-3alkyl)S(═O)2NH(C1-3alkyl), —N(C1-3 alkyl)S(═O)2N(C1-3alkyl)2, —PH(C1-3alkyl), —P(C1-3alkyl)2, —P(═O)H(C1-3alkyl), —P(═O)(C1-3alkyl)2, 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, 3-6 membered heterocyclyl, 6 membered aryl or 5-6 membered heteroaryl;
• Each of (heterocyclyl and heteroaryl) at each occurrence is independently contain 1, 2, 3 or 4 heteroatoms selected from N, O, S, S(═O) or S(═O)2.