3-Amino-1,4-dimethyl-5H-pyrido

Cl5H17N3O2, 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole acetate,... 

DiMeIQx 2-amino-3,4,8-trimethylimidazo-[/] quinoxaline nh2 Trp-P-1 3-amino-l,4-dimethyl-5H-pyrido[4,3-/)Jindole CH3 0X1. CH3 Trp-P-2 3-amino-l-methyl-5H-pyrido[4,3-/)]indole ch3 f S X" N... 

SYNS 3-. UvtINO-l,4-DIMETHYL-Y-CARBOLINE 3-AMINO-l,4-DIMETHYL-5H-PYRIDO(4,3-b)INDOLE 1,4-DIMETHYL-5H-PYRIDO(4,3-b)lNDOL-3-AMlNE TRP-P-1 dl-TRYPTOPHAN, pyrolyzate 1... 

In relation to food intake, pyrolysis products of L-tryptophan in which highly mutagenic y-carboline, tryptophan-P-1 (3-amino-l, 4-dimethyl-5H-pyrido[4,3-b] indole and tryptophan-P-2 (3-amino-l-methyl-5H-pyrido[4,3-b] indole are formed and can be activated to mutagens in liver. Implications of such events in liver carcinogenesis are discussed in Chapter 6. 

FIGURE 9.3 Total gas chromatogram obtained from standard heterocyclic amines (containing 5 ng of each amine). GC conditions-peaks 1. 2-amino-9H-pyrido[2,3-b]indole (AaC) + 2-aminodipyrido [l,2-a 3 2Cd]imidazole (Glu-p-2) 2. 2-amino-6-methyldipyrido[l,2-a 3 2Cd]imidazole (Glu-P-1) 3. 3-amino-l,4-dimethyl-5H-pyrido[3,4-b]indole (Trp-P-1) 4. 3-amino-l-methyl-5H-pyrido[3,4-b]indole (Trp-P-2) ... 

Amino-l,4-dimethyl-5H-pyrido[4,3-f>]indole Trp-P-1 C33H33N3 211 8.6 Less-polar —... 

Two potent mutagenic principles, 3-ami no-1,4-dimethyl-5H-pyrido(4,3-b)indole, Trp-P-1 and 3-amino-l-methyl-5H-pyrido(4,3-b) indole, Trp-P-2 and two comutagens, Harman and Norharman were found in the pyrolysis of the amino acid, D,L-tfyptophan(l ). 

Z-aminO 1 -methy 1 6 phenylimidazo [4,5-b]-pyridine 2 aminO 3,7,8 trimethylimidazo[4,5 f]quinoxaline 2 aminO 3,4,7,8 tetramethyl 3H imidazO [4,5 f]quinoxaline inoxaline 3 aminO l,4 dimethyl SH pyrid [4,3 b] indole (Trp P I) and 3 aminO l methyl 5H pyrido [4,3 b]indole induced mutagenesis. Metabolic activation was required for positive results b... 

PHAs identified in cooked foods that are of concern to human health include 2-amino-3-methylimidazo[4,5-/Iquinoline (IQ), 2-amino-3,4-dimethyl-3H-imidazo[4,5-/ quinoline (MelQ), 2-amino-3,8-dimethylimidazo[4,5-/Iquinoxaline (MelQx), 2-amino-2,4,8 (or 3,7,8)-trimethylimidazo[4,5-/Iquinoxaline (diMelQx), 2-amino-iV-methyl-5-phenylimidazopyridine (PhIP), 3-amino-l,4-dimethyl-5/f-pyrido[4,3-fe]indole (Trp-P-1), 3-amino-l-methyl-5H-... 

The dimethylamino group in diethyl (2 R=Et) and dimethyl 1-dimethylamino-3-oxobut-l-ene-2,4-dicarboxylates (2 R=Me) can be exchanged very easily with nitrogen nucleophiles. With primary amines in methanol or ethanol under reflux for several hours, substitution of the dimethylamino group by an amine takes place followed by intramolecular nucleophilic attack of the amino group on the ester to afford 1-substituted 5-alkoxycarbonyl-4-hydroxypyridin-2(lH)-ones 56 in 16-93% yields (5cheme 21). In the reaction of 56 with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate (57), first the intermediate 58 was formed, which cyclized into 6-substituted 3-benzoylamino-8-ethoxycarbonyl-2H,5H-pyrido[4,3-li]pyran-2,5-diones (59). However, with 3-dimethyla-mino-2-(methoxycarbonyl)propenoate (60) intermediate 61 is formed... 

However, when 36 was heated with a-amino heterocycles or with cyclic 1,3-dicarbonyl or potential 1,3-dicarbonyl compounds, 3-heteroarylp)rr-azol derivatives were obtained. In this manner 36 afforded, when heated with 2-aminopyridine and 3-amino-lH-pyrazol in acetic acid under reflux for 2 h and 5 h, respectively, 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-4H-pyrido[l,2-fl]pyrimid-4-one (38) and 6-(5-ethoxy-l-phenyl-lH-p5rrazol-3-yl)pyrazolo[l,5-fl]pyrimid-7(lH)-one (39) in 70% and 77% 5deld, respectively. Similarly, 36 afforded with cyclicjS-dicarbonyl compounds, such as 4-hydroxy-6-methyl-2H-pyran-2-one and 5,5-dimethylcyclohexane-l,3-dione by heating in acetic acid for 4 h and 8 h, respectively, the corresponding 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-7-methyl-2H,5H-pyrano[4,3- 7]pyran-2,5-dione (40) and 3-(5-ethoxy-l-phenyl-IH-pyrazol-3-yl)-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5-dione (41) in 26% and 82% yield, respectively (Scheme 15). 

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