Substituted nitrogen heterocyclic compound and anesthetic effect thereof

A compound, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a deuterated derivative thereof, characterized in that:

• the compound is a compound of formula I;
• R1 is deuterium, or substituted or unsubstituted C1-8 alkyls;
• for above R1, said substituents are deuterium;
• n is an integer of 0˜5;
• R2 is C1-8 alkyls;
• K1 is N,
• K2 is N or CRk2;
• K3 is CRk3,
• R is selected from the group consisting of
• Rk2 and Rk3 are independently selected from the group consisting of hydrogen, deuterium, halogen, and C1-8 alkyls;
• X is O or S;
• L1 and L2 are each independently none, or substituted or unsubstituted C1-8 alkylene;
• said substituents are selected from the group consisting of deuterium, cyano, hydroxyl, carboxyl, halogen, CH, CH2, C3-8 alkyls or their halogenated or deuterated derivative, C2-8 alkenyls or their halogenated or deuterated derivative, C2-8 alkynyls or their halogenated or deuterated derivative, C1-8 alkoxyls or their halogenated or deuterated derivative, C3-8 cycloalkyls or their halogenated or deuterated derivative, 3˜8-membered heterocyclic groups or their halogenated or deuterated derivative, aryls or their halogenated or deuterated derivative, and heteroaryls or their halogenated or deuterated derivative;
• L1 and L2 can be connected to the homotopic or heterotopic atoms on the A ring;
• m is an integer of 0˜4;
• ring A is none, or ring A is selected from the group consisting of 3˜8-membered saturated carbocycles, 3˜8-membered unsaturated carbocycles, 3˜8-membered saturated heterocycles, and 3˜8-membered unsaturated heterocycles;
• R5 is selected from the group consisting of hydrogen, deuterium, halogen, propadienyl,
• substituted or unsubstituted C1-8 alkyls, —OR33, —SR33, —OC(O)R34, C3-8-membered cycloalkyls, 3˜8-membered heterocyclyls aryls, heteroaryls, —N(R33)2, —C(O)R34, —C(S)R34, —S(O)R34, —CON(R33)2, —SO2R34, substituted or unsubstituted C2-8 alkenyls, substituted or unsubstituted C2-8 alkynyls, cyano, isocyano, isothiocyano, nitro, -L33-R36 and ═R39;
• L33 is C1-4 alkylene;
• R36 is selected from the group consisting of cyano, nitro, —OC(O) R34, —C(O)R34, —S(O)R34, and —C(O)N(R33)2;
• R33 is selected from the group consisting of hydrogen, methylsulfonyl, -L31-COO-L32, and the following substituted or unsubstituted groups:
• C1-8 alkyls, C3-8 cycloalkyls, 3˜8-membered heterocyclyls, aryls, or heteroaryls;
• R34is selected from the group consisting of R33, deuterium, and the following substituted or unsubstituted groups:
• C1-8 alkoxyl, C2-8 alkenyls, C2-8 alkynyls, or —S—C1-8 alkyls;
• L31 is substituted or unsubstituted C1-8 alkylene;
• L32 is substituted or unsubstituted C1-8 alkyls;
• for above R5, R33, R34, said substituents are selected from the group consisting of deuterium, cyano, hydroxyl, carboxyl, halogen, C1-4 alkyls or their halogenated or the deuterated derivative, C1-4 alkoxyl or their halogenated or the deuterated derivative, C3-8-membered cycloalkyls or their halogenated or the deuterated derivative, 3-8-membered heterocyclyls or their halogenated or the deuterated derivative, aryls or their halogenated or deuterated derivative, heteroaryls or their halogenated or deuterated derivative, —S—C1-4 alkyls, di-substituted cyclic carbonyls, ═R39, C2-8 alkenyls, and C2-8 alkynyls;
• R39 is selected from the group consisting of O, S, NR40, and C(R41)2;
• wherein R40 is selected from the group consisting of hydrogen, halogen, and C1-4 alkyls or their halogenated or deuterated derivative;
• R41 is R40 or deuterium;
• R0 is LC3RC4, or LC1XCLC2RC5;
• LC3 is none, or substituted or unsubstituted C1-4 alkylene, said substituents in C1-4 alkylenyls are selected from the group consisting of C1-5 alkyls, C1˜5 alkoxyl, halogen, and hydroxyl;
• RC4 is selected from the group consisting of substituted or unsubstituted C2˜6 alkenyls, substituted or unsubstituted C2-6 alkynyls, substituted or unsubstituted 3˜6-membered saturated or unsaturated heterocyclyls, substituted or unsubstituted 3˜6-membered saturated or unsaturated cycloalkyls, and COR4d;
• said substituents are each independently LC4R4e;
• R4d is C1˜6 alkyls;
• LC4 is none, or substituted or unsubstituted C1-4 alkylene;
• R4e is selected from the group consisting of C1-5 alkyls, C1˜5 alkoxyl, halogen, and hydroxyl;
• LC1 is substituted or unsubstituted C1-3 alkylene, said substituents is C1-5 alkyls;
• XC is O or S;
• LC2 is none, or substituted or unsubstituted C1-3 alkylene, said substituents are selected from the group consisting of C1-4 alkyls, C1-4 alkoxyl, and L2aR5g;
• wherein L2a is none, or C1˜2 alkylene;
• R5g is halogen, or C1˜4 alkoxyls;
• RC5 is selected from the group consisting of hydrogen, halogen, C1˜5 alkyls, C2˜4 alkenyls, C2˜4 alkynyls, COR4d, C3˜6 di-alkenyls, C1˜5 alkoxyl, 3˜6-membered saturated or unsaturated heterocyclyls optionally substituted by one or more R5c, 3˜6-membered saturated or unsaturated cycloalkyls optionally substituted by one or more R5c;
• wherein R4d is C1-6 alkyls, R5c is selected from the group consisting of halogen, =R5d, L1aR5e, and C3˜6di-alkenyls;
• R5d is CH2, O or S, L1a is C1-3 alkylene, and R5e is C1˜5 alkyls, or C1˜5 alkoxyl;
• MD is CO or CRD6RD7, wherein RD6 is hydrogen, or XDbRD4b, RD7 is hydrogen, or XDcRD4c;
• XD is O or S;
• XDb is O or S;
• XDc is O or S;
• Ra is selected from the group consisting of substituted or unsubstituted C1˜6 alkyls, substituted or unsubstituted C2˜6 alkynyls, substituted or unsubstituted C2˜6 alkenyls, substituted or unsubstituted 3˜6-membered saturated or unsaturated heterocyclyls, and substituted or unsubstituted 3˜6-membered saturated or unsaturated cycloalkyls;
• said substituents are each independently selected from the group consisting of C3˜6 di-alkenyls, C1˜5 alkyls, C1˜5 alkoxyl, halogen, and hydroxyl;
• RD4b and RD4c are each independently selected from the group consisting of substituted or unsubstituted C1−6 alkyls, substituted or unsubstituted C2˜6 alkynyls, substituted or unsubstituted C2˜6 alkenyls, CORDf, substituted or unsubstituted 3≣6-membered saturated or unsaturated heterocyclyls groups, and substituted or unsubstituted 3˜6-membered saturated or unsaturated cycloalkyls;
• said substituents are each independently selected from the group consisting of C3−6 dialkenyls, C1˜5 alkyls, C1˜5 alkoxyl, halogen, and hydroxyl;
• RDf is C1-5 alkyls.