ANTIMICROBIAL AND ANTITUMOR PHENAZINE CARBOXALDEHYDES AND DERIVATIVES

摘要

There is disclosed a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein
R1 is hydrogen or methyl;
R2 is oxygen, =N-Y-NR4R5, in which Y is cyclohexyl or a straight or branched alkylene of from one to six carbon atoms optionally substituted with hydroxyl, and in which R4 and R5 are independently hydrogen, or alkyl of from one to four carbon atoms, optionally substituted with hydroxyl, or R2 is =N(CH2)n-W in which n is zero or an integer of from one to four and W is a pyrrolidinyl or piperidinyl ring optionally substituted with alkyl of from one to four carbon atoms which may be further substituted with hydroxyl;
R3 is hydroxy, alkoxy of from one to four carbon atoms -NH-Y min -NR4 min R5 min , in which Y min is cyclohexyl or a straight or branched alkylene of from one to six carbon atoms optionally substituted with hydroxyl, and in which R4 min and R5 min are independently hydrogen, alkyl of from one to four carbon atoms optionally substituted with hydroxyl, or R3 is -NH(CH2)n min -W min in which n min is zero or an integer of from one to four and W min is a pyrrolidinyl or piperidinyl ring optionally substituted with alkyl of from one to four carbon atoms which may be further substituted with hydroxyl;
with the proviso that when R1 is hydrogen and R2 is oxygen, R3 may not be hydroxy or alkoxy.
The compounds are derived from 6-formyl-4,7,9-trihydroxy-1phenazinecarboxylic acid, methyl ester and from 6-formyl-4,7,9-trihydroxy-8-methyl-1phenazine-carboxylic acid; methyl ester and demonstrate anti-microbial and anti-neoplastic activity.
In addition a purified strain of Streptomyces galanosa, NRRL 15738, is capable of producing 6-formyl-4,7,9-trihydroxy-8-methyl-1 phenazinecarboxylic acid, methyl ester in isolable quantities from a fermentation broth containing assimilable sources of carbon and nitrogen.