Pyridine 1 -methyl-4-phenyl-1,2,3,4-tetrahydro

Fig. 9. Chemical structure of the synthetic neurotoxin l-methyl-4-phenyl-tetrahydro-pyridine (MPTP) and its metabolism, with monoamine oxidase B as substrate, via MPDP+ to the methyl-phenyl-pyridinium ion (MPP+), which is the active toxin. (For further details see Feldman (1997).)...

Grunblatt E, Mandel S, Maor G, Youdim MB. 2001. Gene e]q>ression analysis in N-methyl-4-phenyl- 1,2,3,6-tetrahydro-pyridine mice model of Parkinson s disease using cDNA microarray effect of R-apomorphine. J Neurochem 78 1. 

Hazell AS, Itzhak Y, Liu HP, Norenberg MD (1997) l-Methyl-4-phenyl-l,2,3,6-tetrahydro-pyridine (MPTP) decreases glutamate uptake in cultured astrocytes. J Nem-ochem 68 2216-2219... 

Benzoyl-l-(4-brom-phenyl)-4,5-dimethyl-l. 2,3,6-tetrahydro-pyridin (52% bez. auf die Gesamtreaktion)2 2- Benzoyl-4,5-dimethyl-1-( 4-methyl-phenyl)-l, 2,3,6-telrahydro-pyridin (36% bez. auf die Gesamtreaktion)2 2-Benzoyl-4,5-dimethyl-l-phenyl-l,2,3,6-tetrahydro-pyridin (52% bez. auf das intermediate O-Silyl-hydroxylamin-Derivat)2... 

Methyl-6-oxo-4-phenyl-l,4,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester... 

Brewster ME, Kaminski JJ, Bodor N. Reactivity of biologically important reduced pyridines. 2. The oxidation of l-methyl-4-phenyl-l,2,3,6-tetrahydro-pyridine. J Am Chem Soc 1988 110 6337-6341. 

Stromberg I, Bjorklund H, Dahl D, Jonsson G, Sundstrom E, Olson L (1986) Astrocyte responses to dopaminergic denervations by 6-hydroxydopamine and l-methyl-4-phenyl-l,2,3,6-tetrahydro-pyridine as evidenced by glial fibrillary acidic protein immunohis-tochemistry. Brain Res Bull 17 225-236. 

Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the l-methyl-4-phenyl-l,2,3,6-tetrahydro-pyridine model of Parkinson s disease. Proc Natl Acad Sci USA 100 6145-6150. 

Graham WC, Robertson RG, Sambrook MA et al (1990) Injection of excitatory amino acid antagonists into the medial pallidal segment of a l-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. Life Sci 47 PL91-PL97... 

When o-(2-aminoethyloxy)benzophenone (27) was refluxed in pyridine, the cychc imine (28) was generated, which was then methylated and reduced with LiAlH4 to give the 5-phenyl-tetrahydro-... 

Insight into the environmental causes of PD was obtained in the 1980s when it was shown that an impurity in synthetic heroin, l-methyl-4-phenyl-l,2,5,6-tetrahydro-pyridine (MPTP), a substance chemically similar to several pesticides, caused severe Parkinsonism in addicts who used this drug intravenously [31, 32]. It has been subsequently shown that exposures to pesticides [32-34], some heavy metals [35, 36], and volatile organic solvents [37-39] have resulted in increased incidences of PD. 

Oxazolo[4,5-6]pyridin-2(3 H)-one IR, 6, 653 <76HCA1593) Oxazolo[4,5-fi]pyridin-2(3H)-one, 3-(4-chlorophenyl)-3a,7a-dihydro-6-methyl-X-ray, 6, 647 <79CPB2261) Oxazolo[4,5-6]pyridin-2(3H)-one, 3-(4-chlorophenyl)-3a,7a-dihydro-7a-methyl-X-ray, 6, 647 <79CPB2261) 5H-Oxazolo[3,2-a]pyridin-3(2H)-one, 2-phenyl-6,7,8,8a-tetrahydro-X-ray, 6, 646 <77MI42902) Oxazolo[5,4-d]pyrimidin-4-amine, A7-methyl- H NMR, 6, 650 <70BCJ3909)... 

Chemical Name 2,3,4,9-tetrahydro-2-methyl-9-phenyl-1 H-indeno[2,1, c] pyridine tartrate Common Name 2-methyl-9-phenyl-2,3,4,9-tetrahydro-Tpyridindene tartrate Structural Formula CcH, ... 

Chemical Name 2,3,4,9-Tetrahydro-2-methyl-9-phenyl-lH-indeno[2,l,c]pyridine tartrate... 

Hydroxy-2-methyl-3-phenylpropyl)amino]pyridine (24) underwent dehy-drative cyclization to give 3-methyl-4-phenyl-l,2,3,4-tetrahydro-l,5-naphthyridine (25) (70% H2S04, 0°C —>25°C, 15h 65%) that was easily dehydrogenated to give 3-methyl-4-phenyl-l,5-naphthyridine (26) (neat substrate, Pd/C, 200°C, 3 h 56%).879 Also other examples.48 485 865 967 1232 1245... 

A-(6-Chloronaphthalen-2-)sulfonylpiperazine derivatives 4 and 5 (Figure 15.12) are potent factor Xa inhibitors. Haginoya et al proposed to replace the pyridine-phenyl or the pyridine-piperidine residue by a fused-bicyclic ring which contains an aliphatic amine and a pyridine to yield the compound 6 that has an interesting factor Xa inhibitor activity. The bioisosteric replacement of the pyridine moiety of the 6-methyl-5,6,7,8-tetrahydro-[l,6]naphthyridine by phenyl, thiophene, or thiazole analogs yielded analogs with similar or better antifactor Xa activity, but also to conserve a moderate bioavailability. 

Cbz Cp DABCO DBU DDQ (DHQD)2CLB (DHQD)2PYR DMF DME DMPU DMSO Et Fmoc HMPA ia KHMDS LDA LiHMDS Me MEM Ms NaHMDS Ph Piv PMB Pr Py (saltmen)Mn(N) benzyloxy carbonyl p 5 -cyclopentadienyl l,4-diazabicyclo[2.2.2]octane l,8-diazabicyclo[5.4.0]undec-7-ene 2,3 -dichloro-5,6-dicyanobenzoquinone dihydroquinidinyl p-chlorobenzoale (see Chart 1) dihydroquinidinyl pyrimidine (see Chart 1) dimethylformamide dimethoxyethane l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone dimethylsulfoxide ethyl 9-fluorenylmethoxy carbonyl hexamethylphosphoric triamide inverse addition potassium hexamethyldisilazide lithium diisopropylamide lithium hexamethyldisilazide methyl (2-methoxy ethoxy )methyl methanesulfonyl sodium hexamethyldisilazide phenyl pivaloyl p -methoxy benzyl propyl pyridine nitrido[A,A/-(l,l,2,2-tetramethyl) bis(salicylideneaminato)]manganese (see Chart 1)... 

---