Preparation of purine derivatives that expand hematopoietic stem cells.

Abstract

The invention relates to compds. of formula I and compns. for expanding the no. of CD34+ cells for transplantation. The invention further relates to a cell population comprising expanded hematopoietic stem cells (HSCs) and its use in autologous or allogeneic transplantation for the treatment of patients with inherited immunodeficient and autoimmune diseases and diverse hematopoietic disorders to reconstitute the hematopoietic cell lineages and immune system defense. Compds. of formula I wherein G1 is N and CR3; G2, G3 and G4 are independently CH and N, with the proviso that at least one of G3 and G4 is N, and that G1 and G2 are not both N; L is NH(CH2)0-3 and derivs, NHCH(CO2Me)CH2 and derivs., NH(CH2)2NH and derivs., etc.; R1 is H, Ph, thienyl, furanyl, etc.; R2 is SO2NH2 and derivs., NHCONH2 and derivs., Ph, etc.; R3 is H, C1-4 alkyl and biphenyl; R4 is C1-10 alkyl, prop-1-en-2-yl, cyclohexyl, cyclopropyl, etc.; and salts thereof, are claimed. Example compd. II was prepd. by alkylation of 2,6-dichloro-9H-purine with 2-iodopropane; the resulting 2,6-dichloro-9-isopropyl-9H-purine underwent amination with tyramine to give 4-(2-(2-chloro-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol, which underwent cross-coupling with benzothiophene-3-boronic acid to give compd. II. All the invention compds. were evaluated for their ability fo facilitate hematopoietic stem cell expansion (some data given). [on SciFinder(R)]