Dithioamine reducing agents

摘要

Dithioamine reducing agents useful for the reduction of disulfide bonds. The reducing agents of this invention are useful, for example, to reduce disulfide bonds, particularly in proteins, or to prevent the formation of disulfide bonds, particularly in proteins and other biological molecules. Reducing agents of this invention are useful and suitable for application in a variety of biological applications, particularly as research and synthetic reagents. The invention provides S-acylated dithioamines which can be selectively activated reducing agents by removal of the S-acyl groups enzymatically or chemically. The invention further provides dithiane precursors of thioamino reducing agents. The invention provides dithioamine reducing agents, S-acylated dithioamines and dithianes which are immobilized on surfaces, including among others, glass, quartz, microparticles, nanoparticles and resins.

主权项

1. A compound having formula I or II: or salts thereof where: R1 is hydrogen, or an unsubstituted alkyl group having 1 to 3 carbon atoms; each R2 and R3 is independently hydrogen, an alkyl group having 1-3 carbon atoms, a phenyl or a benzyl group each of which is optionally substituted with one or more of substituents W2; each R4 and R5 is hydrogen; each R6 and R7 is independently hydrogen, a 1-12 carbon alkyl group, an aryl group, a heterocyclic group, a heteroaryl group, a —CO—NHR11 group, a —CO—NHR11 group, a —SO2—R11 group, or a —(CH2)n—R12 group, wherein n is an integer ranging from 1-12 and each alkyl, aryl heterocylic or heteroaryl group is optionally substituted with one or more of substituents W3; and each R8 is independently hydrogen or —CO—R13, wherein:
each R11 and R12 is independently hydrogen, a 1-12 carbon alkyl group, an aryl group, a heterocyclic group, a heteroaryl group, a -L-T group or a -M group, wherein each alkyl, aryl heterocylic or heteroaryl group is optionally substituted with one or more of substituents W3, -L- is a divalent linker group and T is a biological species or a surface to which the reducing agent is linked and -M is a reactive group or a spacer moiety carrying a reactive group;each R13 is independently hydrogen, a 1-12 carbon alkyl group, an aryl group, a heterocyclic group, or a heteroaryl group, wherein each alkyl, aryl heterocyclic or heteroaryl group is optionally substituted with one or more of substituents W3; wherein;
W2 is one or more substituents selected from halogen, an oxo group (═O), cyano group, nitro group, hydroxyl, unsubstituted alkyl group having 1-3 carbon atoms, halogen-substituted alkyl group having 1-3 carbon atoms, or unsubstituted alkoxy group having 1-3 carbon atoms; andW3 is one or more substituents selected from halogen, an oxo group (═O), cyano group, nitro group, hydroxyl, optionally substituted alkyl group having 1-6 carbon atoms, unsubstituted alkyl group having 1-6 carbon atoms, hydroxyl-substituted alkyl group having 1-6 carbon atoms, halogen-substituted alkyl group having 1-6 carbon atoms, unsubstituted alkoxy group having 1-6 carbon atoms, alkenyl group having 2-6 carbon atoms; alkynyl group having 2-6 carbon atoms, a 3-6-member alicyclic ring, wherein one or two ring carbons are optionally replaced with —CO— and which may contain one or two double bonds, an aryl group having 6-14 carbon ring atoms, a phenyl group, a benzyl group, a 5- or 6-member ring heterocyclic group having 1-3 heteroatoms and wherein one or two ring carbons are optionally replaced with —CO— and which may contain one or two double bonds, or a heteroaryl group having 1-3 heteroatoms (N, O or S), a —CO2R14 group, a —CON(R15)2 group, a —OCON(R15)2 group, a —N(R15)2 group, a —SO2—OR15 group, a —(CH2)m—OR14 group, or a —(CH2)m—N(R15)2, where m is 1-8, and each R14 and R15 is independently hydrogen, an unsubstituted alkyl group having 1-6 carbon atoms; an unsubstituted aryl group having 6-14 carbon atoms, an unsubstituted phenyl group; an unsubstituted benzyl group, an unsubstituted 5- or 6-member ring heterocyclic group, having 1-3 heteroatoms and wherein one or two ring carbons are optionally replaced with —CO— and which may contain one or two double bonds, or a unsubstituted heteroaryl group having 1-3 heteroatoms, with the exception that no R14 is hydrogen, and with the exception that in the compound of formula II not all of R1-R7 are hydrogen.