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A series of TAN-1511 analogues bearing a non-peptide spacer in place of the Gly-Gly-Gly sequence in the peptide moiety was synthesized, and the effects of these compounds on the proliferation of bone marrow cells in culture and experimental leukocytopenia in mice were examined. The structure-activity relationships obtained were as follows. As the substituent at the 2-position of the 4-thiaheptanoic acid framework, an amino group, methyl group or hydrogen was preferable; as a spacer in place of the Gly-Gly-Gly sequence, a 4-aminobenzoyl or 4-aminomethylbenzoyl group was suitable; and as the fatty acids bonded to the 6,7-dihydroxy groups, C16 fatty acid was best. Compounds 12f, 30d and 30i potently promoted the proliferation of bone marrow cells in culture and the restoration of leukocyte counts in a murine leukocytopenia model.
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