Claims
- 1. Compounds of the formula I ##STR6## wherein X represents a linker chain --CR.sub.1 R.sub.2 -- or --CR.sub.1 .dbd.CR.sub.2 -- (where R.sub.1 and R.sub.2 are separately H, lower alkyl, phenyl or nitro-phenyl); Y is halogen or OSO.sub.2 R; Q is lower alkyl (optionally substituted with alkyl and/or ether functions and containing up to 6 carbons) or nitrophenyl; Ar represents a mono- or bicyclic aromatic unit; R is lower alkyl optionally substituted with alkyl and/or ether groups, and may contain up to eight carbon atoms; and Z represents one or more of the groups H, NO.sub.2, SO.sub.2 R, CONHR, R, OR, SR, CF.sub.3 and aza (ring --CH.dbd. replaced by --N.dbd.); with the proviso that when Y=C1 or Br, Q=Me, and X=--CH.sub.2 -- then AR.noteq.2-nitrophenyl or 4-nitrophenyl;
- or pharmaceutically acceptable salts thereof.
- 2. Compounds of claim 1 which are:
- N,N-Bis(2-chloropropyl)-N-methyl-N-(2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-(3-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-clhloroethyl)-N-methyl-N-(3-methyl-2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-(4-methyl-2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-cloroethyl)-N-methyl-N-(5-methyl-2-nitrobenzyl)anmonium chloride;
- N,N-Bis(2-chloroethyl)-N-(3-methoxy-2-nitrobenzyl)-N-methylammonium chloride;
- N,N,-Bis(2-chloroethyl)-N-(4-methoxy-2-nitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-(5-methoxy-2-nitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-(3,5-dinitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-�(4-methylsulfonyl)benzyl! ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-�(5-nitro-1-naphthyl)methyl!ammonium chloride; or
- N,N-Bis(2-chloroethyl)-N-methyl-N-�(8-nitro-1-naphthyl)methyl!ammonium chloride;
- or their pharmaceutically acceptable salts.
- 3. Pharmaceutical compositions comprising a compound of claim 1 together with a pharmaceutically acceptable carrier or diluent.
- 4. Pharmaceutical compositions comprising a compound of claim 2 together with a pharmaceutically acceptable carrier or diluent.
- 5. Compounds of claim 1, wherein Ar is selected from the group consisting of: ##STR7##
- 6. A process for making compounds of the formula I ##STR8## wherein X represents a linker chain --CR.sub.1 R.sub.2 -- or --CR.sub.1 .dbd.CR.sub.2 -- (where R.sub.1 and R.sub.2 are separately H, lower alkyl, phenyl or nitro-phenyl); Y is halogen or OSO.sub.2 R; Q is lower alkyl (optionally substituted with alkyl and/or ether functions and containing up to 6 carbons) or nitrophenyl; Ar represents a mono- or bicyclic aromatic unit; R is lower alkyl optionally substituted with alkyl and/or ether groups, and may contain up to eight carbon atoms; and Z represents one or more of the groups H, NO.sub.2, SO.sub.2 R, CONHR, R, OR, SR, CF.sub.3 and aza (ring --CH.dbd. replaced by --N.dbd.); or pharmaceutically acceptable salts thereof, according to the following reaction scheme ##STR9## comprising reacting aromatic .alpha.-methyl halides of the formula II with N-alkyl- or N-aryldiethanolamines to give the quaternary diols of the general formula III, and converting the quaternary diols of the formula III to the compounds of formula I by treatment with SOCl.sub.2 at room temperature.
- 7. The process of claim 6, wherein Ar is selected from the group consisting of: ##STR10## .
- 8. A method of treatment of neoplastic cells which comprises administering to a patient an effective amount of a compound of formula I ##STR11## wherein X represents a linker chain --CR.sub.1 R.sub.2 -- or --CR.sub.1 .dbd.CR.sub.2 -- (where R.sub.1 and R.sub.2 are separately H, lower alkyl, phenyl or nitro-phenyl); Y is halogen or OSO.sub.2 R; Q is lower alkyl (optionally substituted with alkyl and/or ether groups and containing up to 6 carbons) or nitrophenyl; Ar represents a mono- or bicyclic aromatic unit; R is lower alkyl optionally substituted with alkyl and/or ether groups, and may contain up to eight carbon atoms; Z represents one or more of the groups H, NO.sub.2, SO.sub.2 R, CONHR, R, OR, SR, CF.sub.3 and aza (ring --CH.dbd. replaced by --N.dbd.); and the pharmaceutically acceptable salts thereof.
- 9. The method as claimed in claim 8 wherein the compound is selected from the following compounds:
- N,N-Bis(2-chloroethyl)-N-methyl-N-(2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-bromoethyl)-N-methyl-N-(2-nitrobenzyl)ammonium bromide;
- N,N-Bis(2-chloropropyl)-N-methyl-N-(2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-(3-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-(3-methyl-2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-(4-methyl-2-nitrobenzyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-(5-methyl-2-nitrobenyl)ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-(3-methoxy-2-nitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-(4-methoxy-2-nitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-(5-methoxy-2-nitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-(3,5-dinitrobenzyl)-N-methylammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-�(4-methylsulfonyl)benzyl! ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-�(5-nitro-1-naplhthyl)methyl! ammonium chloride;
- N,N-Bis(2-chloroethyl)-N-methyl-N-�(8-nitro-1-naphthyl)methyl! ammonium chloride;
- and their pharmaceutically acceptable salts.
- 10. The method as claimed in claim 8, further comprising conjuctively administering pharmaceuticals having an inhibitory effect on tumour blood flow and performing radiotherapy treatment.
- 11. The method of claim 8, wherein Ar is selected from the group consisting of: ##STR12## .
Priority Claims (1)
Number |
Date |
Country |
Kind |
245270 |
May 1993 |
NZX |
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Parent Case Info
This application is a division of application Ser. No. 08/525,785, filed Sep. 27, 1995, now U.S. Pat. No. 5,691,371, which was the 35 USC 371 national stage if International application PCT/NZ94/0046 filed on May 24, 1994, which designated the United States.
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Divisions (1)
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Number |
Date |
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Parent |
525785 |
Sep 1995 |
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