Patent EA-000033-B1 (EA)
Title: Bis(2-haloethyl) aminophenyl substituted distamycin derivatives as antitumor and antiviral agents
Inventor: COZZI PAOLO
IPC: C07D207/34
Filed: 1996-06-19
Abstract: 1. Bis (2- haloethyl) aminophenyl substituted distamycin derivatives of formula (I)   wherein n is 1, 2 and 3 one of R and R1 is hydrogen, C1-C4 alkyl, CF3 or C1-C4 alkoxy and the other is independently CF3, C1-C4 alkyl or C1-C4, alkoxy; and X is halogen and the pharmaceutically acceptable salts thereof. 2. A compound of formula (I), according to Claim 1, wherein n is 3; X is chloro; one of R and R1 is hydrogen or C1-C4, alkyl and the other is C1-C4 alkyl, CF3 or C1-C4 alkoxy; and the pharmaceutically acceptable salts thereof. 3. A compound selected from: β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3-methyl-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido]pyrolle-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4- [l-methyl-4-[3,5-dimethyl-4-N,N-bis(2-chloroethyl)aminobenzene-l-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3-ethyl-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3,5-diethyl-4-N,N-bis(2-chloroethyl)obenzene-l-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3-methoxy-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3-ethoxy-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido] pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[2-methoxy-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[2-methyl-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3-trifluoromethyl-4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; and β-[l-methyl-4-[l-methyl-4-[l-methyl-4-[3-trifluoromethyl-5-methyl-4-N,N-bis(2-chloroethyl)aminobenzene-l-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; or a pharmaceutically acceptable salts thereof. 4. A salt of a compound according to Claim 3,wherein said salt is the hydrochloride. 5. A process for the preparation of a compound of formula (I), according to Claim 1, or a salt thereof, as antitumor and antiviral agents. 6. A pharmaceutical composition containing a suitable carrier and/or diluent and, as an active principle, a compound of formula (I) according to Claim 1 or a pharmaceutically acceptable salt thereof. 7. A pharmaceutical composition according to Claim 6, containing an additional antitumor agent thereof, for use in anti-cancer therapy. 8. A method of treating a mammal in need of an antineoplastic agent, the method comprising administering to said mammal a therapeutically effective amount of a compound of formula (I), as defined in Claim 1, or a pharmaceutically acceptable salt thereof.