PROCEDURE FOR THE PROMOTION OF PYRINE-ORIGINAL CLOTHING TIMES

摘要

1504891 Purine nucleotides ICN PHARMACEUTICALS Inc 13 May 1975 [31 May 1974] 20140/75 Heading C2P The invention comprises compounds of formula wherein X is Cl, Br, SR or NR 1 R 2 ; Y is Cl, Br, OH, SR, NH 2 or NR 1 R 2 ; Z is H or NH 2 ; R is H, Ph, CH 2 Ph, C 1-4 alkyl or p-chlorophenyl; R 1 and R 2 are each H, CH 2 Ph or C 1-4 alkyl (at least one being other than H) or NR 1 R 2 is a 5- or 6-membered saturated heterocycle; and RSP1/SP is H or C 1-18 acyl. Preparation (a) from inosine 3SP1/SP,5SP1/SP-cyclic phosphate (cIMP) or guanosine 3SP1/SP,5SP1/SP-cyclic (cGMP) or their 2SP1/SP-acylates by introduction of halo (Cl or Br) into the 6- and 8-positions in separate or simultaneous stages, followed when required by replacement of said halo or other values of X and Y using appropriate nucleophilic reagents; (b) from 8-(Y-substituted)- adenosine 3SP1/SP,5SP1/SP - cyclic phosphates by NSP6/SP- alkylation or benzylation. 21-O-acyl groups may be inserted or removed at any stage. Intermediates: (a) 8-bromo-cIMP 2SP1/SP-(acetate or butyrate) Et 3 N sa (b) 8-hydroxy-cIMP; (c) cGMP 2SP1/SP-butyrate Na sa (d) 8-bromo-cGMP 21- butyrate Et 2 N sa (e) 8-bromo-cGMP; (f) 8 - (p - chlorophenylthio) - cGMP Na sa (g) 8 - (p - chlrophenylthio) - cGMP 2SP1/SP-acetate; (h) 8-(p-chlorophenylthio)-cIMP 2SP1/SP-acetate. Compounds I are credited with phosphodiesterase inhibition, protein kinase activation, positive inotropic, adenyl cyclase inhibition, antiinflammatory and antihypertensive activities.