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

Galceran et al. (199) developed an SPE-HPLC method for the determination in beef extract of five mutagenic amines, namely Trp-P-1 (3-amino-1,4-dimethyl-5//-pyrido[4,3-fc]indole),... 

Trp-P-1 3-amino-1,4-dimethyl-5//-pyrido[4,3-fe]indole Trp-P-2 3-amino-l-methyl-5//-pyrido[4,3-fe]indole Glu-P-1 2-amino-6-methyldipyrido[l,2-a 3, 2 -ct]imidazole Glu-P-2 2-aminodipyrido[ 1,2-a 3, 2 -rf]imidazole Phe-P-1 2-amino-5-phenylpyridine... 

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) ... 

Yamashita et al. (4367, 4368) identified and quantitated the following /V-heterocyclic amines in mainstream CSC 2-amino-3-methylimidazo[4,5-/]quinoline (IQ) (0.3 ng/cigarette), 3-amino-l,4-dimethyl-57/-pyrido[4,3-/>]mdole (Trp-P-1) (0.3 ng/cigarette), 3-amino-l-methyl-5//-pyrido[4,3-fc]indole (Trp-P-2) (0.2 ng/cigarette), 2-amino-9//-pyrido[2,3-fc]indole (AaC) (16.9 ng/cigarette), and 2-amino-3-methyl-9//-pyrido [2,3- ]indole (MeAaC) (1.6 ng/cigarette). 

In an in-house presentation, Rodgman (3253a) discussed the already identified and other possible theoretical relationships between tryptophan and the substituted norharmans, the tryptophan pyrolysis products 3-amino-l,4-dimethyl-5//-pyrido[4,3-/ ]indole (Trp-P-1) and 3-amino-l-methyl-5A-pyrido[4,3-/7]indole (Trp-P-2), the 2-amino-9A-pyrido[2,3-f>] indoles (AaC and MeAaC), indole-3-acetonitrile, and the alkyl- and dialkylindoles. 

Ethyl (3S)-8-amino-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihy-dro-7//-pyrido[l,2,3- f< ]-l,4-benzothiazine-6-carboxylate was obtained by the reduction of the respective 8-nitro derivative (OOMIPIO). 

A-Salicoyl derivatives of 3-amino-2-halopyridines cyclize under basic conditions to pyrido-[2,3-/ ][l, 4]benzoxazcpin-6(5//)-ones this has been shown for the cyclization of 7V-(2-chloro-4,6-dimethyl-3-pyridyl)salicylamide 41... 

The reaction of 2-amino-5,7-dimethyl-1,8-naphthyridine and EMME in boiling Dowtherm A for 45 min gave the pyrido[l,2-o]-1,8-naphthyridine derivative (1602) in 40% yield. The same product (1602) was obtained in 44% yield in the reaction of N-( 1,8-naphthyridin-2-yl)aminomethylene-malonate (1603) and EMME in boiling Dowtherm A for 1 hr. The thermal ring closure of 1603 was unsuccessful. An ethanolic suspension of 1603 was treated with concentrated aqueous ammonium hydroxide at reflux for 24 hr to give 2-aminopyrido[ 1,2-a]-1,8-naphthyridine (1604) in quantitative yield (80FES1052). 

Figure 13.7 Mutagenic and carcinogenic heterocyclic amines of the carboline group (a) AaC (2-amino-9//-p5Tido[2,3,-i)]indole), (b) norharman (9f/-pyrido[4,3-i)]indole), (c) Trp-P-1 (3-amino-l,4-dimethyl-57/-pyrido[4,3-/)]indole), (d) Glu-P-1 (2-amino-6-methyl-dipyrido[l,2-a 3, 2 -d]imidazole).

The reaction of 1-amino-4,6-diphenylpyridine-2(l//)-thione (147) with dimethylformamide dimethyl acetal or triethyl orthoformate afforded 2-phenyl-4//-pyrido[2,l-a]phthalazine-4-thione (148) [81AQ(C)248],... 

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... 

Pyrido[2,3-, pyridazine derivatives 48 have been synthesized by refluxing equimolar amounts of an appropriate 5-benzylidene-2,2-dimethyl-l,3-dioxane-4,6-dione 47 with 5-amino-6-phenylpyridazin-3(2/7)-one 46 in methanol or a methanol acetic acid mixture. The electron-poor carbon atom of the polarized carbon-carbon double bond of 47 is the electrophile attacking C-4 of the 5-aminopyridazinone 46. Imino-enamine tautomerization of the intermediate is followed by ring closure and subsequent loss of acetone and carbon dioxide affording the reaction products 48 as stable crystalline solids in 70-90% yield (Scheme 9) <2000T2473>. 

Carbonyl insertion into 5-substituted 2-(o-bromo-/>-isopropylphenyl-amino)pyridines (275) in the presence of bis(triphenylphosphine)palla-dium(II) chloride, triphenylphosphine, and tributylamine under 200 psi-pressure of carbon monoxide at 100°C in aqueous ferr-butanol or dimethyl-formamide gave 8-substituted 2-isopropyl-l 17/-pyrido[2,l-b]quinazolin-l 1 -ones (276) (87JOC2469). 

Cyclocondensation of 5-halovaleraldehydes (186) and 1,3-amino alcohols (187) gave equilibrium mixtures of tram- and c s-pyrido[2,l-h][l,3]oxazines (188 and 189), with a predominance of the frans-fused bicycle both diastere-omers contained the substituent in the equatorial position (90TL4281 94JA2617,94JOC6904). However, kinetic selectivity for the formation of cis-pyrido[2,l-h][l,3]oxazine (189) was exhibited versus the tram compound 188 in the case of the dimethyl derivative (R = R1 = Me) (90TL4281). 

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... 

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