AGONISTS THAT ENHANCED BINDING OF INTEGRIN-EXPRESSING CELLS TO INTEGRIN RECEPTORS

摘要

A method of enhancing binding of cells to an integrin-binding ligand comprises treating integrin-expressing cells in vitro with an agonist of integrin, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the treated cells with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells or agonist compounds to a mammal.

主权项

1. A chemical compound having the general formula (I) wherein R1 is -substituted phenyl, or a substituted or unsubstituted heterocyclic aromatic group, R2 is aralkyl, M1 is CH2, M2 is CO, M3 is absent or is O or CH2, M4 is absent or is CH2, M5 is absent or is O or (CR11R12), R11, when present, is hydrogen, R12, when present, is selected from the group consisting of hydrogen, NR21CONR22R23, NR21COR24, NR21SO2R24 and NR21COOR24, M6 is selected from the group consisting of (CH2)q, (CH2)qCH═CH(CH2), (CH2)q arylene(CH2)r and (CH2CH2O)q, wherein q and r are independently integers from 0 to 6, R3 is CONR13R14, R21 and R22, each of which when present, is independently selected from the group of hydrogen and C1-C6 alkyl, R13, R14, R23 and R24, each of which when present, is independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl and aralkyl, and R1, R2, R13, R14, R23 and R24, when present, may be either unsubstituted or substituted with one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylaryl, hydroxy, alkoxy, azido, haloalkoxy, hydroxyalkyl, aryloxy, hydroxyaryl, alkoxyaryl, halo, haloalkyl, haloaryl, amino, alkylamino, dialkylamino, arylamino, diarylamino, —NHCO(alkyl), —NHCO(aryl), —NHCO(aralkyl), —NHCO(haloalkyl), —NHSO2(alkyl), —NHSO2(aryl), —NHSO2(aralkyl), alkoxycarbonyl, alkoxycarbonylalkyl, —OCO(alkylamino), and —OCO(dialkylamino).