Substituted 1,2,3-triazoles as antibacterial and antifungal pleuromutilin conjugates

A compound according to Formula (1):

• or a pharmaceutically acceptable salt or stereoisomer thereof,
• wherein:
• (i) X is C1-C5alkylene, C2-C5alkenylene, C2-C5alkynylene, —NH—, —O—, or —S—;
• wherein the —NH—is optionally substituted with one substituent selected from the group consisting of D and C1-C3alkyl;
• and
• wherein the C1-C5alkylene, C2-C5alkenylene, or C2-C5alkynylene is optionally substituted with one or more substituents independently selected from the group consisting of D, F, Cl, Br, and I;
• and R1 is F, Cl, Br, I, CN, NO2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, CH(NH), C(O)H, C(O)NH2, C(O)NHNH2, C(O)OH, C(O)OC1-6alkyl, C(O)OC2-6alkenyl, C(O)OC2-6alkynyl, C(O)SH, C(O)phenyl, C(O)aminophenyl, C(O)hydroxyphenyl, C(O)methoxyphenyl, C(O)pyridinyl, C(O)aminopyridinyl, C(O)hydroxypyridinyl, C(O)methoxypyridinyl, C(O)pyridazinyl, C(O)aminopyridazinyl, C(O)hydroxypyridazinyl, C(O)methoxypyridazinyl, C(O)pyrimidinyl, C(O)aminopyrimidinyl, C(O)hydroxypyrimidinyl, C(O)methoxypyrimidinyl, C(O)pyrazinyl, C(O)aminopyrazinyl, C(O)hydroxypyrazinyl, C(O)methoxypyrazinyl, NH2, NHC1-C6alkyl, NHC1-C6aminoalkyl, NHC(NH)NH2, N(C1-C6alkyl)2, OH, OC1-C6alkyl, SH, S(O)2OH, C3-C8cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, or OC1-C6alkyl is optionally substituted with one or more substituents independently selected from the group consisting of D, F, Cl, Br, I, CN, NO2, CH(NH), C(O)H, C(O)NH2, C(O)NHNH2, C(O)OH, C(O)OC1-6alkyl, C(O)OC2-6alkenyl, C(O)OC2-6alkynyl, C(O)SH, NH2, NHC1-C6alkyl, NHC1-C6aminoalkyl, NHC(NH)NH2, N(C1-C6alkyl)2, OH, OC1-C6alkyl, SH, S(O)2OH, C3-C8cycloalkyl, piperazinyl, aryl, and heteroaryl;
• wherein the C3-C8 cycloalkyl or heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of D, F, Cl, Br, I, CN, NO2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, CH(NH), C(O)H, C(O)NH2, C(O)NHNH2, C(O)OH, C(O)OC1-6alkyl, C(O)OC2-6alkenyl, C(O)OC2-6alkynyl, C(O)SH, NH2, NHC1-C6alkyl, NHC1-C6aminoalkyl, NHC(NH)NH2, N(C1-C6alkyl)2, OH, OC1-C6alkyl, ═O, SH, S(O)2OH, C3-C8cycloalkyl, piperazinyl, aryl, and heteroaryl;
• wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, F, Cl, Br, I, CN, NO2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, CH(NH), C(O)H, C(O)NH2, C(O)NHNH2, C(O)OH, C(O)OC1-6alkyl, C(O)OC2-6alkenyl, C(O)OC2-6alkynyl, C(O)SH, NH2, NHC1-C6alkyl, NHC1-C6aminoalkyl, NHC(NH)NH2, N(C1-C6alkyl)2, OH, OC1-C6alkyl, SH, S(O)2OH, C3-C8cycloalkyl, piperazinyl, aryl, and heteroaryl;
• and
• wherein each piperazinyl substituent is optionally and independently substituted with one or more independently selected C1-C5alkyl substituents;
• or
• (ii) XR1 is CN;
• ring A is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of D, F, Cl, Br, I, CN, NO2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C(O)NH2, C(O)OH, NH2, NHC1-C6alkyl, N(C1-C6alkyl)2, OH, OC1-C6alkyl, C3-C8cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• —is a single bond;
• and
• Ra is H, C1-C5alkyl, C1-C5aminoalkyl, C1-C5hydroxyalkyl, NH2, OH, OCH3, or OCH2CH3.