EP 1701743 A2 20060920 - POTENTIATION OF THE ACTIVATION OF HIGH-MOLECULAR-MASS PRODRUGS
Title (en)
POTENTIATION OF THE ACTIVATION OF HIGH-MOLECULAR-MASS PRODRUGS
Title (de)
VERSTÄRKUNG DER AKTIVIERUNG VON HOCHMOLEKULAREN PRODRUGS
Title (fr)
POTENTIALISATION DE HAUT POIDS MOLECULAIRE
Publication
Application
Priority
- FR 2004002162 W 20040819
- FR 0310114 A 20030822
Abstract (en)
[origin: FR2858936A1] Compound (X) that comprises an agent, active on target cells, linked to a cleavable residue that increases its half-life in the circulation is new. Compounds of formula (A) p-(E-B) n-(I) m (X) are new. I : active compound; A : group that increases half-life of B-I in the circulation; E-B : linking group; B : structure that can be cleaved selectively by an enzyme present only, or preferentially, close to, or at, the target cells; E : hydrophilic spacer, stable in the circulation, which separates A and B so as to permit, or facilitate, cleavage of B close to, or at, the target cells, allowing release of I, optionally together with B; n : integer from 1 to the total number of reactive functional groups of I to which E-B are, or could be, attached; m : integer from 1 to the total number of reactive functional groups on A to which E-B could be attached; and p : integer from 1 to the total number of reactive functional groups of I to which E-B could be attached. Provided that: (1) when p is 1, then n equals m; and (2) when m is 1, then p is 1. ACTIVITY : Cytostatic; Antiinflammatory. Athymic mice carrying a subcutaneous graft of the human colon carcinoma LS-174T were treated with (i) succinyl-beta -Ala-Leu-Ala-Leu-Dox (= doxorubicin) or (ii) poly(ethylene glycol) (PEG) 2000-(D-Ser) 4-Ala-Leu-Ala-Leu-Dox, intravenously, on days 0, 7, 14 and 21. The specific growth delay for (i) was 1.27 (phase 1) and 3.02 (phase 2), for total Dox dose 5 mu mole; for (ii) 0.87 and 1.58, respectively (total Dox dose 3.875 mu mole) and for free Dox (0.669 mu mole; a single dose) 0.53 and 1.86. MECHANISM OF ACTION : None given.
IPC 8 full level
A61K 47/48 (2006.01)
CPC (source: EP)
A61K 47/60 (2017.07); A61K 47/643 (2017.07); A61K 47/65 (2017.07); A61P 43/00 (2017.12)
Citation (search report)
See references of WO 2005021043A2
Designated contracting state (EPC)
AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PL PT RO SE SI SK TR
DOCDB simple family (publication)
FR 2858936 A1 20050225; AU 2004268405 A1 20050310; BR PI0413843 A 20061024; CA 2536442 A1 20050310; EP 1701743 A2 20060920; IL 173760 A0 20060705; JP 2007503382 A 20070222; WO 2005021043 A2 20050310; WO 2005021043 A3 20060615
DOCDB simple family (application)
FR 0310114 A 20030822; AU 2004268405 A 20040819; BR PI0413843 A 20040819; CA 2536442 A 20040819; EP 04786328 A 20040819; FR 2004002162 W 20040819; IL 17376006 A 20060216; JP 2006523656 A 20040819