Posaconazole derivative, pharmaceutical composition and use thereof

A compound represented by formula (I), a racemate, stereoisomer, tautomer, or a pharmaceutically acceptable salt thereof:

• wherein, R is
• which are unsubstituted or substituted with one or more Ra or Rb;
• Rt is
• X1 and X2 are independently chosen from F, Cl, Br, or I;
• X3 is a pharmaceutically acceptable anion;
• R1 is Rh;
• Rh is
• O(O)C(NH2)CH2OH, or —OS(O)2OM3;
• R2 and R4 are independently H or C1-40 alkyl that is unsubstituted or substituted with one or more Ra;
• R3 is a C1-40 alkyl that is unsubstituted or substituted with one or more Rb;
• R5 and R6 are independently H, or independent chosen from the following groups that are unsubstituted or optionally substituted with one or more Rm:
• C1-40 alkyl, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, or —C(O)Rf;
• Ar is chosen from the following groups that are unsubstituted or substituted with one or more Rc:
• C6-20 aryl, 5-20 membered heteroaryl, wherein the heteroaryl has 1-5 heteroatoms independently chosen from N, O, or S;
• R7 is chosen from the following groups that are unsubstituted or substituted with one or more Rc:
• C1-40 alkyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, —Y2P(O)(OM1)(OM2), —C(O)Rf, or —(CH2CH2O)z—Rb, wherein z is an integer of 1 to 10;
• R8 is H, or chosen from the following groups that are unsubstituted or substituted with one or more Rb:
• C1-40 alkyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, NRdRe, —CONRdRe, —C(O)Y2Rf, —Y2(O)CRf, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• R9 is chosen from the following groups that are unsubstituted or substituted with one or more Rb:
• R10—Y3—Y4—, R11—C(O)—Y5—Y6—, C1-40 alkyl, C1-40 alkoxy, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, —Y2—N(R4)—C(═NH)—NH2, —Y3—N(R2)—C(O)—Y2—N(R4)—C(═NH)—NH2, or —(CH2CH2O)z—H, wherein z is an integer of 1 to 10;
• R10 and R11 are independently H, or are chosen from the following groups that are unsubstituted or substituted with one or more Rb:
• C1-40 alkyl, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• Y1, Y2, Y3, Y4, Y5 and Y6 are independently chosen from a chemical bond, —O—, —S— or the following groups that are unsubstituted or substituted with one or more Ra:
• —NH—, C1-40 alkyl, C1-40 alkoxy, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, or —(CH2CH2O)m, wherein m is an integer of 0 to 10;
• provided that, when two or more of Y1, Y2, Y3, Y4, Y5 and Y6 are adjacent, the adjacent groups are not chemical bonds at the same time;
• each Ra is independently chosen from H, C1-40 alkyl, C1-40 alkoxy, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, F, Cl, Br, I, OH, SH, CN, ═O, NRdRe, —C(O)Y2Rf, —Y2(O)CRf, —CONRdRe, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• each Rb is independently chosen from H, F, Cl, Br, I, OH, SH, CN, or the following groups that are unsubstituted or substituted with one or more Ra:
• C1-40 alkyl, C1-40 alkoxy, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, C3-20 cycloalkyloxy, 3-20 membered heterocyclyl, 3-20 membered heterocyclyloxy, C6-20 aryl, C6-20 aryloxy, 5-20 membered heteroaryl, 5-20 membered heteroaryloxy, NRdRe, —CONRdRe, —C(O)Y2Rf, —Y2(O)CRf, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• each Rc is independently chosen from F, Cl, Br, I, OH, SH, CN, or the following groups that are unsubstituted or substituted with one or more Ra:
• C1-40 alkyl, C1-40 alkoxy, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, NRdRe, —CONRdRe, —C(O)Y2Rf, —Y2(O)CRf, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• each Rd and Re are independently H, or chosen from the following groups that are unsubstituted or substituted with one or more Rm:
• C1-40 alkyl, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, —CONRfRg, —C(O)Y2Rf, —Y2(O)CRf, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• each Rf and Rg are independently H, or chosen from the following groups that are unsubstituted or substituted with one or more Rm:
• C1-40 alkyl, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, COOH, 3-20 membered heterocyclyl, C6-20 aryl, or 5-20 membered heteroaryl;
• each Rm is independently chosen from H, F, Cl, Br, I, OH, SH, CN, or the following groups that are unsubstituted or substituted with one or more Ra:
• C1-40 alkyl, C1-40 alkoxy, C2-40 alkenyl, C2-40 alkynyl, C3-20 cycloalkyl, 3-20 membered heterocyclyl, C6-20 aryl, 5-20 membered heteroaryl, NRdRe, —CONRdRe, —C(O)Y2Rf, Y2(O)CRf, —Y2P(O)(OM1)(OM2), or —Y2S(O)2OM3;
• M1, M2, and M3 are independently selected from H or C1-40 alkyl that is unsubstituted or substituted with one or more Rb;
• provided that when R is
• R1 is not hydroxyl;
• and when Rt is
• R3 is not —CH2NHCH3;
• wherein the heterocyclyl and heteroaryl are independent from each other and each has 1-5 heteroatoms independently chosen from N, O or S.