Substantially cell membrane impermeable compound and use thereof

A method for preparing a compound according to the Formula (I):

• A-(L-Y)p
• Wherein:
• A is selected from the group consisting of glutathione, glucosamine, cysteinyiglycine, cysteic acid, aspartic acid, glutamic acid, lysine, and arginine, and wherein the sulfur atom of each sulfur containing compound may be optionally oxidized to form a sulfbxide or sulfone;
• L corresponds to (XBX′)nB′, and wherein
• n is an integer from 0 to 20,
• X is selected from the group consisting of:
• NR—, S(O)—, —S(O)O—, —S(O)2—, —S(O)2O—, —C(O)—, —C(S)—, —C(O)O—, C(S)O—, —C(S)S—, —P(O)(R1)—, —P(O)(R1)O—, or is absent;
• B is selected from C1—C10 alkylene, C2—C10 alkenylene, C2—C10 alkynylene, C3C10 cycloalkylene, C5—C10 cycloalkenylene, C3C10 heterocycloslkylene, C5—C10 heterocycloalkenylene, C6—C12 arylene, heteroazylene or C2—C10 acyl;
• X′ is selected from NR—, —O—, —S—, —Se—, —S—S—, S(O)—, —OS(O)—, OS(O)O—, OS(O)2, —OS(O)2O—, —S(O)O—,—S(O)2—, —S(O)2O—, —OP(O)(R1)O—, —OP(O)(R1)—OP(O)(R1)O—, —C(O)—, —C(S)—, —C(O)O—, C(S)O—, —C(S)S—, —P(O)(R1)—, —P(O)(R1)O—,
• or is absent;
• wherein E is O, S, Se, NR or N(R)2−;
• and
• B′ is C1—C10 alkenylene, C2—C10 alkynylene, C3—C10 alkynylene, C3—C10 cycloalkylene, C5—C10 cycloalkonylene, C3—C10 heterocycloalkylene, C5 —C10 heterocycloalkenylene, C6—C12 arylene, heteroarylene or is absent;
• and wherein
• each R is independently selected from hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 heterocycloalkyl, C6—C12 aryl, heteroaryl, OR2 or C2—C10 acyl;
• R′ is the same as R or two R′ may be taken together with the nitrogen atoms to which they are attached to form a 5 or 6-membered saturated or unsaturated heterocyclic ring;
• each R1 is independently selected from hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl, halo, OR2 or NO2;
• each R2 is independently selected from hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl or —C(O)R5;
• each R5 is independently selected from hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl, C1—C10 alkoxy, C3—C10 alkenyloxy, C3—C10 alkynyloxy, C3—C10 cycloalkyloxy, C5—10 cycloalkenyloxy, C3—C10 heterocycloalkyloxy, C5—C10 heterocycloalkenyloxy, C6—C12 aryloxy, heteroaryloxy, C1—C10 alkylthio, C3C10 alkenylthio, C3—C10 cycloalkylthio, C5—C10 cycloalkenylthio, C3—C10 heterocycloalkylthio, C5—C10 heterocycloalkenylthio, C6—C12 arylthio, heteroarylthio, OH, SH or NO2;
• wherein for each instance that B and/or B′ is arylene, the substituents directly attached to the respective arylene rings (including arsenoxide), may be in a para, meta or ortho relationship, and
• wherein each alklene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene, heteroarylene and acyl may be independently substituted with hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl, halo, cyano, cyanate, isocyanate, OR2a, SR6, nitro, arsenoxide, —S(O)R3, —OS(O)R3, —S(O)2R3, —OS(O)2R3, —P(O)R4R4, —OP(O)R4R4, —N(R″)2, —NRC(O)(CH2)mQ, —C(O)R5,
• wherein R, R1 and R5 are as defined above;
• and
• R2a is selected from hydrogen, C1—C5 alkyl, C2—C5 alkenyl, C2—C5 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C6—C12 aryl, —S(O)R3, —S(O)2R3, —P(O)(R4)2, N{circle around (R)}2or —C(O)R5;
• each R3 is independently selected from hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl, C1—C10 alkoxy, C3—C10 alkenyloxy, C3—C10 alkynyloxy, C3—C10 cycloalkyloxy, C5—C10 cycloalkenyloxy, C3—C10 heterocycloalkyloxy, C5—C10 heterocycloalkenyloxy, C6—C12 aryloxy, heteroaryloxy, C1—C10 alkylthio, C3—C10 alkenylthio, C3—C10 alkynylthio, C3—C10 cycloalkylthio, C5C10 cycloalkenylthio, C3—C10 heterocycloalkylthio, C5—C10 heteroalkenylthio, C6—C12 arylthio, heteroarylthio or NO2;
• each R4 is independently selected from hydrogen, C1—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycoalkyl, C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl, C1—C10 alkoxy, C3—C10 alkenyloxy, C3—C10 alkynyloxy, C3—C10 cycloalkyloxy, C5—C10 cycloalkenyloxy, C3—C10 heterocycloalkyloxy, C5—C10 heterocycloalkenyloxy, C6—C12 aryloxy, heteroaryloxy, C1—C10 alkylthio, C3—C10 alkenylthio, C3—C10 alkynylthio, C3—C10 cycloalkylthio, C5—C10 cycloalkenylthio, C3—C10 heterocycloalkythio, C5—10 heterocycloalkenylthio, C6—C12 arylthio, heteroarylthio, halo or NO2;
• R6 is selected from C3—C10 alkyl, C2—C10 alkenyl, C2—C10 alkynyl, C3—C10 cycloalkyl, C5—C10 cycloalkenyl, C3—C10 heterocycloalkyl, C5—C10 C5—C10 heterocycloalkenyl, C6—C12 aryl, heteroaryl, C1—C10 alkylthio, C3—C10 alkenylthio, C3—C10 alkynylthio, C3—C10 cycloalkylthio, C5—C10 cycloalkenylthio, C3—C10 heterocycloalkylthio, C5—C10 heterocycloalkenylthio, C6—C12 arylthio, heteroarylthio, —S(O)R3, —S(O)2R3 or —C(O)R5,
• R″ is the same as R or two R″ taken together with the N atom to which they are attached may form a saturated, unsaturated or aromatic heterocyclic ring system;
• Q is selected from halogen and —OS(O)2Q1;
• wherein Q1 is selected from C1—C4 alkyl, C1—C4 perfluoroalkyl, phenyl, p-methylphenyl;
• and
• m is 1 to 5,
• Y comprises at least one arsenoxide;
• and
• p is an integer from 1 to 10;
• and wherein the sum total of carbon atoms in A and L together, is greater than 6;
• said method comprising reacting at least one of said substantially cell-membrane impermeable groups (A) with said spacer group L to which is attached at least one arsenoxide (Y).