Acridine-4-carboxamides

Schofield, P. C., Robertson, I. G., and Paxton, J. W. (2000) Inter-species variation in the metabolism and inhibition of N-[(2"-dimethylamino)ethyl]acridine-4-carboxamide (DACA) by aldehyde oxidase. Biochem. Pharmacol. 59 (2), 161-165. 

Fig. 5.3 Radiolabeling of anti-cancer drugs for pharmacokinetic studies. DACA, /V-[2-(dimethyl-ami no)]acridine-4-carboxamide.

Saleem, A., Harte, R. J., Matthews, J. C., Osman, S., Brown, G.D., Bleehen, N., Connors, X, Jones, X, Price, P.M., and Aboagye, E.O. Pharmacokinetic evaluation of N-[2-(Dimethyl-amino)ethyl]acridine-4-carboxamide (DACA XR5000) in patients by positron emission tomography. J. Clin. Oncol., 19 1421-1429, 2001. 

Scheme 22 shows acridines with carbonyl groups in position 4. The acridine-4-carboxamides 62, either unsubstituted as shown (n = 2—6) or bearing one methoxy group in position 1, 2, 5, 6, or 7, respectively, have been examined as antitumor agents. DACA (n = 2) has been under clinical... 

A-acetoxy-lV-/e//-butoxybenzamide, 55 /V-acyloxy- /V-alkoxyalky lam ides, 55 /V- acy I o x y- /V-a I k o x y u re as, 56 /V-chlorohydroxamic esters, 56 N, /V-dialkoxyamidcs, 56 Intercalative guest molecules, binding dynamics of DNA with, 186-201 acridine derivatives, 190-194 9-aminoacridine carboxamide derivatives, 194, 195... 

Substitution of the nine position is a common transformation for acridines. An optimized method for preparing the 9-carboxamides uses BOP/DMF <99SC4341>. Reaction of 9-isothioacridines with the sodium anion of diethylmalonate is followed by alkylation with bromoacetate to afford the spiro[dihydroacridine-9(10i/)-thiazolidines] <99H(51)137>. 

SYNS ACRIDINE-9-CARBOXAMIDE, 1,2,3,4-TETRAHYDRO-N,N-DIETHYL- KETONE, DIETHYLAMINO(l,2,3,4-TETRAHYDRO-9-ACRIDINYL)... 

A variation on the Pfitzinger acridine nthesis utilises the reaction between isatin, cyclohexanone and ammonia to yield l,2,3,4-tetrahydroacridine-9-carboxamides (24) directly (J. Bielavsky, Coll. Czech, chem. Comm., 1977, 42, 2802). Hofmann degradation of the amides yields the partially reduced 9-aminoacridines. 

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