Imidazoles. II. 5(or 4)-(Monosubstituted Triazeno)imidazole-4(or 5)-carboxamides¹

Abstract

Several 5 (or 4)-(3-alkyl-3-methyl-l-triazeno)imidazole-4 (or 5)-carboxamides (111-X) were prepared from 5-diazoimidazole-4-carboxamide and the appropriate N-alkyl methylamine. Most of these derivatives significantly increased the life span of leukemic (L1210) mice. Inhibition of the growth of sarcoma 180, adenocarcinoma 755, and Walker carcinosarcoma 256 was observed, but inhibition of solid tumors was generally accompanied by large, adverse, host-weight changes. Qualitative observations of the sensitivity to light of aqueous alcoholic solutions of the dimethyltriazeno (NSC-4 5 388) and the butylmethyltriazeno derivatives indicate a pronounced variation in stability with the kind of light exposure. EPRESENTATIVES OF BOTH disubstituted-

Preclinical, phase I and pharmacokinetic studies with the dimethyl phenyltriazene CB10-277

“…Numerous compounds with structural similarities to dacarbazine that have preclinical activity exist (Loo & Lin, 1972;Audette et al, 1973;Connors et al, 1976;Loo et al, 1976;Giraldi et al, 1977;Hatheway et al, 1978;Wilman & Goddard, 1980;Gescher et al, 1981;Shealy & Krauth, 1966;Vaughn et al, 1984). CB10-277, a phenyl dimethyltriazene, is soluble and stable in aqueous solutions at physiologic pH (Wilman & Goddard, 1980).…”

“…The basic triazene structure is shown in Figure 1. Compounds with different R, substitutents in position at N' (Loo & Lin, 1972;Audette et al, 1973;Connors et al, 1976;Loo et al, 1976;Giraldi et al, 1977;Hatheway et al, 1978;Wilman & Coddard, 1980;Gescher et al, 1981) and R2 and R3 substituents at N3 (Audette et al, 1973;Connors et al, 1976;Hatheway et al, 1978;Wilman & Goddard, 1980;Gescher et al, 1981;Shealy & Krauth, 1966;Vaughn et al, 1984) have been studied by various groups for activity in animal tumours. While a range of structural variations at RI can be tolerated, it is generally accepted that at least one methyl group is required at either R2 or R3 in order to allow the formation of a monomethyl species for antitumour activity (Audette et al, 1973).…”

“…Dacarbazine undergoes in vitro decomposition in aqueous solution at physiologic pH (Shealy & Krauth, 1966). These decomposition products are not thought to contribute to in vivo antitumour activity (Julliard & Vernin, 1981).…”

Evaluation of Novel Imidazotetrazine Analogues Designed to Overcome Temozolomide Resistance and Glioblastoma Regrowth

“…At neutral pH, TMZ is moderately unstable (t 1/2 = 1.24 h, pH 7.4) (4) and is hydrolyzed in a ring-opening reaction to the open chain triazene MTIC (Figure S2A; t 1/2 = 8 min, pH 7.4) (5) that fragments to the reactive electrophile, methyldiazonium (t 1/2 = 0.39 s, pH 7.4) (6-8). The methyldiazonium ion reacts with nucleophilic groups on DNA, resulting in DNA methylation.…”

Synthesis and Spectral Identification of Novel Stable Triazene: As Raw Material for the Synthesis Biocompatible Surfactants-Pyrazole-Isoxazole-Dihydropyrimidine-Tetrahydropyridine Derivatives

“…The azo-proteins formed in this way arise largely from diazo-coupling with the activated aromatic rings of tyrosine and histidine residues and the ε-amino group of lysines [14] [15]. Thus, the reaction of aryldiazonium salts 2a with glycine ethyl ester hydrochloride in aqueous solution containing sodium acetate, the diazonium ion attacks at the NH 2 moiety to affords stable triazene derivative 3a and shows no tendency to attack at the activated CH 2 , which would give rise to hydrozone formation [16]- [19], based on its spectral data. For example, the 1 H-NMR spectrum of compound 3a recorded in DMSO-d 6 revealed the presence of a triplet signal at δ = 1.17 ppm corresponding to methyl group, a quartet signal at δ = 4.13 ppm corresponding to methylene group, a singlet signal at δ = 5.02 ppm corresponding to methylene group, a multiplet signal at δ = 6.53 -8.22 ppm corresponding to aromatic protons and a singlet signal at δ = 12.62 ppm corresponding to NH.…”