Mobilization of hematopoietic stem cells

A method for facilitating hematopoietic reconstitution of peripheral blood precursor cells in a subject's hematopoietic organs, comprising:

• a) administering to the subject an effective amount of at least one Cdc42-specific inhibitor in the precursor cells;
• b) isolating mobilized peripheral blood precursor cells from the peripheral circulation of the subject;
• and c) infusing the isolated mobilized peripheral blood precursor cells into the subject, wherein said at least one Cdc42-specific inhibitor is selected from the group of compounds having the structure of Formula (I):
• as a single isomer, a mixture of isomers, a racemic mixture of isomers, pharmaceutically acceptable salt, a solvate, metabolite or polymorph thereof, wherein:
• Y is selected from the group consisting of OR7, NR8R9, and NNR8R9;
• R7 is selected from the group consisting of C1-6 alkyl, (CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl, C1-6 alkyl substituted with up to 5 fluoro, and C1-6 alkoxy substituted with up to 5 fluoro, said C1-6 alkyl, (CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl are each optionally substituted with one or more substitutents each independently selected from the group consisting of halo, —CN, —OH, C1-6 alkoxyl, heteroaryl, R19, and OR20;
• R8 and R9 are each separately a hydrogen, or separately selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, and phenyl, said C1-6 alkyl, C3-7 cycloalkyl, and phenyl, each optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, —(CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, R19, OR20, C1-6 alkyl substituted with up to 5 fluoro, and C1-6 alkoxy substituted with up to 5 fluoro, each optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, and C1-6 alkoxy;
• or R8 and R9 are optionally taken together with the nitrogen to which they are attached to form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, each optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, (CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl, C1-6 alkyl substituted with up to 5 fluoro, and C1-6 alkoxy substituted with up to 5 fluoro;
• or R8 and R2 come together to be C1-3 alkyl linking together as a ring;
• each u is independently 0, 1, 2, 3, or 4;
• R2 is a hydrogen, or selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, and phenyl, said C1-6 alkyl, C3-7 cycloalkyl, and phenyl, each optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, —(CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl, C1-6 alkyl substituted with up to 5 fluoro, C1-6 alkoxy substituted with up to 5 fluoro, and —O(CH2)uphenyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, and C1-6 alkoxy;
• or R8 and R2 come together to be C1-3 alkyl linking together as a ring;
• R3, R4, R5 and R6 are each independently selected from the group consisting of:
• hydrogen, halo, cyano, nitro, hydroxy, C1-6 alkyl, (CH2)uC3-7cycloalkyl, —O(CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl, C1-6 alkyl substituted with up to 5 fluoro, and C1-6 alkoxy substituted with up to 5 fluoro, said C1-6 alkyl, (CH2)uC3-7cycloalkyl, —O(CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, and phenyl, each optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, —(CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl, C1-6 alkyl substituted with up to 5 fluoro, and C1-6 alkoxy substituted with up to 5 fluoro, said phenyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl, —(CH2)uC3-7cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, phenyl, C1-6 alkyl substituted with up to 5 fluoro, and C1-6 alkoxy substituted with up to 5 fluoro;
• R19 is aryl optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl optionally substituted with up to 5 fluoro, and C1-6 alkoxy optionally substituted with up to 5 fluoro;
• R20 is hydrogen or aryl optionally substituted with one or more substituents each independently selected from the group consisting of halo, cyano, nitro, hydroxy, C1-6 alkyl optionally substituted with up to 5 fluoro, and C1-6 alkoxy optionally substituted with up to 5 fluoro;
• and
• wherein when Y is NR8R9 then R8 and R2 optionally come together to be C1-3 alkyl linking together as a ring,
• with the proviso when R8 comes together with R2 to be C1-3 alkyl linking together as a ring then R4, is not substituted with hydroxyl.